Improving regioselectivity of phenylalanine aminomutase from Taxus chinensis by semi-rational mutagenesis for the biocatalytic amination of cinnamates.

The occupancy of the binding pocket by the substrate ultimately determines the outcome of enzyme catalysis. Previous engineering and substrate scope of phenylalanine aminomutase from Taxus chinensis (TcPAM) has generated valuable knowledge about the regioselectivity with biocatalytic potentials for the preparation of α- and ß-phenylalanine and their derivatives. However, the significantly different regioselectivity during the amination of cinnamates by TcPAM is not fully understood. In this study, we take a reconstruction approach to change the whole binding pocket of TcPAM for probing the factors affecting the regioselectivity, resulting in variant C107S/Q319M/I431V reaching a 25.5-fold enhancement of the ß/α product ratio toward trans-cinnamate acid. Furthermore, when substituted cinnamates were used as substrates, the regioselectivity was strongly correlated with various changes in the binding pocket, and value-added 2-Cl-α-Phe (100% α-selectivity) and 4-CH3-ß-Phe (98% ß-selectivity) were individually verified by the mutants L104A and Q319M at a preparative scale, exemplifying the application feasibility of our engineering strategy. The present study uncovered the cooperative connection between aromatic binding and carboxylate binding to affect the regioselectivity, which provides new insights into the determinants of the regioselectivity possessed by TcPAM and paves the way for its biocatalytic applications on phenylalanine derivatives.

Effects of the supernatant of Chlorella vulgaris cultivated under different culture modes on lettuce (Lactuca sativa L.) growth.

CO2 capture by microalgae is a feasible strategy to reduce CO2 emissions. However, large amounts of cell-free supernatant will be produced after microalgal harvesting, which may be harmful to the environment if it is disorderly discharged. In this study, Chlorella vulgaris (C. vulgaris) was cultivated under three common cultivation modes (autotrophic culture (AC), heterotrophic culture (HC) and mixotrophic culture (MC)), and the obtained supernatant was used as fertilizer to investigate its effect on the growth of lettuce. The biomass concentration of C. vulgaris cultivated under MC and HC was 3.25 and 2.59 times that of under AC, respectively. The contents of macronutrients in supernatant obtained from AC were higher than those of MC and HC. However, the contents of amino acids and hormones in supernatant obtained from MC and HC were higher than those of AC. The fresh shoot weight, fresh root weight and root length of lettuce treated with supernatant were significantly higher than that of control treatment. In addition, the contents of chlorophyll, soluble sugar and soluble protein in lettuce treated with supernatant were also higher than that of control treatment. However, the contents of nitrate in lettuce treated with supernatant was lower than that of control treatment. These results showed that the supernatant could promote the growth of lettuce and was a potential of fertilizer for crop planting.

GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in breast cancer patients.

Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70- and Ku80-dependent manner, and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.

Harnessing Lecanicillium attenuatum: A novel strategy for combatting Nilaparvata lugens in rice fields.

Nilaparvata lugens is a notorious rice pest causing significant annual yield and economic losses. The use of entomopathogenic fungi offers a promising and eco-friendly approach to sustainable pest management programs. However, research in this area is currently limited to a few specific types of insects and other arthropods. This study aimed to analyze the biocontrol potential of Lecanicillium attenuatum against N. lugens. Bioassays showed that L. attenuatum 3166 induced >80% mortality in N. lugens following 7 d exposure. Greenhouse and field investigations demonstrated that L. attenuatum 3166 application leads to a substantial reduction in N. lugens populations. Under greenhouse conditions, fluorescence was detected in GFP-labeled L. attenuatum 3166 hyphae enveloping the bodies of N. lugens. In field trials, L. attenuatum 3166 treatment exhibited a control efficacy of up to 68.94% at 14 d post-application, which was comparable to that of the commercial entomopathogenic fungal agent. Genomic sequencing of L. attenuatum 3166 revealed a comprehensive array of genes implicated in its infestation and lethality. Further, the transcriptome sequencing analysis highlighted the elevated expression levels of genes encoding proteases, chitinases, cutinases, and phospholipases. Our findings highlight the potential of L. attenuatum 3166 as an effective biological control agent against N. lugens.

Poisoning Mechanism Map for Metal Hydride Hydrogen Storage Materials.

The effective utilization of hydrogen storage materials (HSMs) is hindered by impurity gas poisoning, posing a significant challenge for large-scale applications. This study elucidates the poisoning mechanisms of various impurities gases (CO, CO2, O2, Ar, He, CH4, N2) on ZrCo, Pd, U and LaNi5. Impurities gases are categorized into active and inactive types based on their effecting behaviors and mechanisms on the hydrogenation of HSMs. During the hydrogenation process, active impurities chemically poison the hydrogenation reaction by limiting hydrogen absorption at interface, while inactive impurities physically hinder hydrogenation reaction by impeding hydrogen diffusion in hydrogen-impurity mixed gas. In situ Scanning Tunneling Microscope clarifies these behaviors, and a novel criterion based on hydrogen spontaneous dissociation energy is introduced to explain and predict impurity-substrate interaction characteristics. The novel findings of this work provide a comprehensive framework for designing long-lived HSMs with poisoning resistance, guiding the development of more resilient hydrogen storage systems.

CSV-Filter: a deep learning-based comprehensive structural variant filtering method for both short and long reads.

MOTIVATION: Structural variants (SVs) play an important role in genetic research and precision medicine. As existing SV detection methods usually contain a substantial number of false positive calls, approaches to filter the detection results are needed. RESULTS: We developed a novel deep learning-based SV filtering tool, CSV-Filter, for both short and long reads. CSV-Filter uses a novel multi-level grayscale image encoding method based on CIGAR strings of the alignment results and employs image augmentation techniques to improve SV feature extraction. CSV-Filter also utilizes self-supervised learning networks for transfer as classification models, and employs mixed-precision operations to accelerate training. The experiments showed that the integration of CSV-Filter with popular SV detection tools could considerably reduce false positive SVs for short and long reads, while maintaining true positive SVs almost unchanged. Compared with DeepSVFilter, a SV filtering tool for short reads, CSV-Filter could recognize more false positive calls and support long reads as an additional feature. AVAILABILITY AND IMPLEMENTATION: https://github.com/xzyschumacher/CSV-Filter.

Optimizing tomato waste hydrolysate for enhanced fucoxanthin biosynthesis in mixotrophic cultivation of Isochrysis galbana.

Vegetable waste, rich in bioactive compounds, offers a promising resource for producing value-added products. This study explored the use of tomato waste, containing glucose (40 mg/g), lycopene (95.12 µg/g), and ß-carotene (24.31 µg/g), for cultivating fucoxanthin-rich Isochrysis galbana. Water-soluble lycopene (2.0 µg/mL) and ß-carotene (0.4 µg/mL) effectively upregulated key carotenoid synthesis genes and boosted cell growth and fucoxanthin production (3.64 and 3.60 pg/cell, respectively) within 10 days in a mixotrophic culture. Optimized tomato waste hydrolysate achieved a high cell density of 1.21 × 107 cells/mL, 2.13 g/L biomass, and 21.02 mg/g fucoxanthin. This study highlights the potential of combining tomato waste with microalgae for a novel and innovative approach towards waste management and resource utilization.

Racial/ethnic disparities in all-cause and cause-specific death among children with malignant central nervous system tumours: a registry-based cohort retrospective analysis.

Background: It is generally recognized that there is unequal mortality in childhood central nervous system (CNS) malignancy in the United States (US), but little is known about the trends and contributors of racial/ethnic disparities in death. We assessed the trends of racial/ethnic disparities in all-cause and cause-specific death, and the contributions of tumour, treatment and socioeconomic factors to this disparity. Methods: This registry-based cohort study included children (aged ≤19 years) diagnosed with malignant CNS tumours, using data from the US population-based cancer registry in the Surveillance, Epidemiology, and End Results (SEER) Program. The clinical outcomes were all-cause and cause-specific death for each racial/ethnic group (White, Black, Hispanic, non-Hispanic Asian/Pacific Islander [API], and non-Hispanic American Indian/Alaska Native [AI/AN] children). We quantified absolute disparities using absolute rate difference in 5-year cumulative incidence of death. Cox proportion risk models were used to estimate the relative racial/ethnic disparities, and the contribution of factors to disparities in death. Findings: In this study, data from 14,510 children with malignant CNS tumours (mean [SD] age, 8.5 [5.7]; 7988 [55.1%] male) were analysed. Overall, the cumulative incidence of death from CNS tumours across four racial/ethnic groups decreased from 2001 to 2020. Black patients had the highest risk of death from all causes and CNS tumours between 2001 and 2020, with adjusted hazard ratios (HR) of 1.52 (1.38-1.68) and 1.47 (1.31-1.64), respectively. The absolute disparity in all-cause death between Hispanic and White patients increased slightly (from 8.2 percentage points [ppt] to 9.4 ppt), and the relative disparity in death from CNS tumours increased from 1.33 (1.15-1.55) in 2001-2005 to 1.78 (1.44-2.20) in 2016-2020. The absolute disparities in death from CNS tumours between Black and White patients (from 11.8 ppt to 4.3 ppt) and between API and White patients (from 10.1 ppt to 5.1 ppt) decreased from 2001-2005 to 2011-2015. Interpretation: Race/ethnicity disparities in death from CNS tumours among childhood malignant CNS tumours had reduced from 2001 to 2020, and quantifying the contribution of factors to this disparity in death could provide a basis for decreasing mortality among racial/ethnic minority patients. Funding: Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program.

Comparative Insecticidal Activity and Mechanism of Isocycloseram versus Other GABAergic Insecticides against the Fall Armyworm.

The fall armyworm (FAW) is a serious agricultural pest and has developed resistance to multiple insecticides. It is necessary to introduce novel insecticide(s) for controlling FAW. Isocycloseram is a completely novel isoxazoline insecticide. However, its activity and mode of action against FAW have not been reported. In this study, isocycloseram exhibited a higher insecticidal activity (LC50 = 0.26 mg/kg) than fipronil (LC50 = 7.72 mg/kg) against FAW. The median inhibitory concentration (IC50) of isocycloseram (IC50 = 8.52 nM) was almost equal to that of the desmethyl-broflanilide (IC50 = 7.32 nM) to the SfrRDL1 receptor. The IC50 of isocycloseram to the SfrRDL2 receptor was 11.13 nM, which was obviously less than that of desmethyl-broflanilide, dieldrin, fipronil, fluxametamide. Compared with the SfrRDL2 receptor, the SfrRDL1 receptor exhibited higher sensitivity to GABAergic insecticides. The recombinant SfrGluCl receptor was successfully stimulated by l-glutamate; however, the currents were low and weakly inhibited by isocycloseram at 10 µM. In conclusion, our results provided the theoretical basis for usage of GABAergic insecticides for controlling FAW.

Carbon-14 labeled transformation of atrazine in soils: Comparison of superabsorbent hydrogel coating and technical material.

Atrazine exhibits adverse effects on diverse organisms in both terrestrial and aquatic environments, even though it effectively targets specific organisms. This study employed superabsorbent hydrogels to coat 14C-atrazine coupled with a four-compartment model to determine the fate of this herbicide in three oxic soils over a 100-day incubation period. Mineralization of atrazine was limited in all soils, with rates remaining below 3.5 %. The encapsulation treatment reduced mineralization of atrazine in soil A and soil B. Bound residues ranged from 26.1 to 43.6 % at 100 d. The encapsulation treatment enhanced the degradation of atrazine and reduced the content of deethylatrazine in soil A, but significantly increased the content of deisopropylatrazine in soil A and hydroxyatrazine in soil C. Using the obtained data, we also constructed a four-compartment model to clarify the relationships among the parent compound, degradation products, bound residues, and mineralization. This model accurately fits the fate of atrazine in the present work. Additionally, the correlation study suggested that both soil parameters and superabsorbent hydrogels played significant roles in influencing atrazine transformation. These findings serve as a reference for evaluating the environmental impact of superabsorbent hydrogels in atrazine pollution reduction and offer a foundational model approach for a comprehensive understanding of organic pollutants.

Thermophilic bacterial agent inoculation enhances biodrying of kitchen waste: Insights into process properties, organic degradation, bacterial communities and metabolic pathways.

The high moisture content of kitchen waste (KW) restricts the future treatment and resource utilization. Biodrying is an effective approach to remove the water of KW. However, conventional biodrying only uses the heat generated by the indigenous microorganisms to remove water, which has long treatment cycle and low moisture removal rate. Microbial bioaugmentation is an emerging approach to improve the biodrying efficiency of KW. In this study, a thermophilic bacterial agent (TBA) composed of Bacillus, Geobacillus and Acinetobacter was used to promote water evaporation during the biodrying process. Based on the results, the moisture removal rate of experimental group inoculated with TBA was 82.20 %, which was notably higher than CK group without inoculation. Moreover, TBA significantly increased the amount of organic matter degradation. Microbial community analysis revealed that TBA could promote the proliferation of thermophilic bacteria and make bacterial community more tolerant to high temperature environment. Further analysis of metabolic pathways showed that quorum sensing and glyoxylate and dicarboxylate metabolism were enhanced by TBA inoculation, which can help microorganisms to better adapt to high temperature environment and release more energy to facilitate the water evaporation. This study offers a fresh approach to improve the water removal efficiency in biodrying process.

Semi-supervised learning with flexible threshold for non-intrusive load monitoring.

Non-intrusive load monitoring (NILM) can obtain fine-grained power consumption information for individual appliances within the user without installing additional hardware sensors. With the rapid development of the deep learning model, many methods have been utilized to address NILM problems and have achieved enhanced appliance identification performance. However, supervised learning models require a substantial volume of annotated data to function effectively, which is time-consuming, laborious, and difficult to implement in real scenarios. In this paper, we propose a novel semi-supervised learning method that combines consistency regularization and pseudo-labels to help identification of appliances with limited labeled data and an abundance of unlabeled data. In addition, given the different learning difficulties of various appliance categories, for example, feature learning is more difficult for multi-state appliances than two-state appliances, the thresholds employed for different appliances are adjusted in a flexible way at each time step so that the informative unlabeled data and their pseudo-labels can be delivered. Experiments have been conducted on publicly available datasets, and the results indicate that the proposed method attains superior appliance identification performance compared to cutting-edge methods.

Impact of superabsorbent hydrogels on microbial community and atrazine fate in soils by 14C-labeling techniques.

The accumulation of atrazine in soils can create environmental challenges, potentially posing risks to human health. Superabsorbent hydrogel (SH)-based formulations offer an eco-friendly approach to accelerate herbicide degradation. However, the impact of SHs on soil microbial community structure, and thus on the fate of atrazine, remains uncertain. In this study, a radioactive tracer was employed to investigate the influence of SHs on microbial communities and atrazine transformation in soils. The results revealed that the mineralization of atrazine in active soils was considerably greater than that in sterilized soils. Atrazine degradation proceeded rapidly under SH treatment, indicating the potential of SH to accelerate atrazine degradation. Furthermore, SH addition did not alter the atrazine degradation pathway in soils, which included dealkylation, dechlorination and hydroxylation. The relative abundance of dominant microbial population was influenced by the presence of SHs in the soil. Additionally, SH application led to an increased relative abundance of Lysobacter, suggesting its potential involvement in atrazine degradation. These findings reveal the significance of soil microorganisms and SH in atrazine degradation, offering crucial insights for the development of effective strategies for atrazine remediation and environmental sustainability.

N-Doped Carbon Modified (NixFe1-x)Se Supported on Vertical Graphene toward Efficient and Stable OER Performance.

NiFe-based nanomaterials are extensively studied as one of the promising candidates for the oxygen evolution reaction (OER). However, their practical application is still largely impeded by the unsatisfied activity and poor durability caused by the severe leaching of active species. Herein, a rapid and facile combustion method is developed to synthesize the vertical graphene (VG) supported N-doped carbon modified (NixFe1-x)Se composites (NC@(NixFe1-x)Se/VG). The interconnected heterostructure of obtained materials plays a vital role in boosting the catalytic performance, offering rich active sites and convenient pathways for rapid electron and ion transport. The incorporation of Se into NiFe facilitates the formation of active species via in situ surface reconstruction. According to density functional theory (DFT) calculations, the in situ formation of a Ni0.75Fe0.25Se/Ni0.75Fe0.25OOH layer significantly enhances the catalytic activity of NC@(NixFe1-x)Se/VG. Furthermore, the surface-adsorbed selenoxide species contribute to the stabilization of the catalytic active phase and increase the overall stability. The obtained NC@(NixFe1-x)Se/VG exhibits a low overpotential of 220 mV at 20 mA cm-2 and long-term stability over 300 h. This work offers a novel perspective on the design and fabrication of OER electrocatalysts with high activity and stability.

Research progress on nonsteroidal anti-inflammatory drugs in the treatment of pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumor is the third most common primary intracranial tumor. Its main clinical manifestations include abnormal hormone secretion symptoms, symptoms caused by tumor compression of the surrounding pituitary tissue, pituitary stroke, and other anterior pituitary dysfunction. Its pathogenesis is yet to be fully understood. Surgical treatment is still the main treatment. Despite complete resection, 10%-20% of tumors may recur. While dopamine agonists are effective in over 90% of prolactinomas, prolonged use and individual variations can lead to increased drug resistance and a gradual decline in efficacy, which ultimately requires surgical intervention. Nonsteroidal anti-inflammatory drugs reduce the production of inflammatory mediator prostaglandins by inhibiting the activity of cyclooxygenase and exert antipyretic, analgesic, antiplatelet, and anti-inflammatory effects. In recent years, many in-depth studies have confirmed the potential of nonsteroidal anti-inflammatory drugs as a preventive and antitumor agent. It has been extensively utilized in the prevention and treatment of various types of cancer. However, their specific mechanisms of action still need to be fully elucidated. This article summarizes recent research progress on the expression of cyclooxygenase in pituitary neuroendocrine tumors and the treatment of nonsteroidal anti-inflammatory drugs. It provides a feasible theoretical basis for further research on pituitary neuroendocrine tumors and explores potential therapeutic targets.

A repeated strike loading organ culture model for studying compression-associated chronic disc degeneration.

Mechanical stress has been viewed as one of the key risk factors in accelerating the intervertebral disc degeneration process. The goal of the present study was to employ a repeated strike loading bovine caudal disc system to elucidate the pathophysiological impacts of cumulative mechanical stress on the disc. The discs in the model groups were subjected to two different mechanical stresses: one strike loading or repeated strike loading. The following indices were analyzed: histological morphology, glycosaminoglycan release, disc height, cell viability, apoptosis-related protein expression, and catabolism-related gene expression. Both mechanical stress modes induced degenerative changes in the discs by day 11, such as clefts and delamination of the annulus fibrosus; they increased glycosaminoglycan release. Cell viability was significantly decreased and catabolic gene expression was significantly up-regulated in the degenerative loading group and repeated strike loading group by day 9. These alterations remained evident in the annulus fibrosus tissue of the repeated strike loading group on day 11. Our data suggests that the repeated strike loading model adopted in this study could lead to degenerative changes in the disc organ model. Annulus fibrosus cells displayed a more noticeable response to mechanical stress damage and a slower recovery process, suggesting that the annulus fibrosus serves as a pivotal factor in disc degeneration due to mechanical stress injuries. The study also indicates that due to the gradual self-repair of intervertebral disc cells after injury, it is necessary to apply repeated strike loading on the disc at specific intervals when researching the repair of chronic disc injuries.

Identification of a Novel ECM Remodeling Macrophage Subset in AKI to CKD Transition by Integrative Spatial and Single-Cell Analysis.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development.

Control efficacy and joint toxicity of broflanilide mixed with commercial insecticides to an underground pest, the black cutworm in highland barley.

BACKGROUND: The highland barley, Hordeum vulgare L., is a staple food crop with superior nutritional functions in Xizang, China. It is often damaged by the black cutworm, Agrotis ipsilon (Hufnagel), which is an underground pest and difficult to effectively manage. To introduce a novel insecticide with unique mode of action, broflanilide (BFL) and its binary mixtures with chlorantraniliprole (CAP), fluxametamide, ß-cypermethrin or imidacloprid were screened out as seed treatment to control black cutworm in highland barley in the present study. RESULTS: In the laboratory bioassays, BFL had outstanding insecticidal activity to black cutworm with a median lethal dose (LD50) of 0.07 mg kg-1. The mixture of BFL × CAP at the concentration ratio of 7:40 exhibited the highest synergistic effect with a co-toxicity coefficient of 280.48. In the greenhouse pot experiments, BFL and BFL × CAP seed treatments at 8 g a.i. kg-1 seed could effectively control black cutworm, with a low percentage of injured seedlings <20% and high control efficacies of 93.33-100% during a period of 3-12 days after seed emergence. Moreover, BFL and BFL × CAP seed treatments could promote the seed germination and seedling growth of highland barley at the tested temperatures of 15, 20 and 25 °C. CONCLUSION: Our results indicated that BFL and BFL × CAP were effective and promising insecticides as seed treatment to control black cutworm in highland barley. © 2024 Society of Chemical Industry.

Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging.

INTRODUCTION: Heterotopic ossification of the tendon and ligament (HOTL) is a chronic progressive disease that is usually accompanied by thickening and ossification of ligaments and high osteogenic activity of the surrounding ligament tissue. However, the molecular mechanism of maintaining the cellular phenotype of HOTL remains unclear. MATERIALS AND METHODS: We first constructed a model of HOTL, Enpp1flox/flox/EIIa-Cre mice, a novel genetic mouse system. Imaging, histological, and cell-level analyses were performed to investigate the progressive ossification of the posterior longitudinal ligament, Achilles tendons, and degeneration joints caused by Enpp1 deficiency. RESULTS: The results indicate that Enpp1 deficiency led to markedly progressive heterotopic ossification (HO), especially spine, and Achilles tendons, and was associated with progressive degeneration of the knees. The bone mass was decreased in the long bone. Furthermore, fibroblasts from Enpp1flox/flox/EIIa-Cre mice had greater osteogenic differentiation potential following induction by osteogenesis, accompanied by enhanced hedgehog (Hh) signaling. In addition, fibroblast cells show senescence, and aggravation of the senescence phenotype by further osteogenic induction. CONCLUSION: Our study indicated that with increasing age, mutations in Enpp1 promote ectopic ossification of spinal ligaments and endochondral ossification in tendons and further aggravate knee degeneration by upregulating hedgehog signaling.

Prochloraz induced alterations in the expression of mRNA in the reproductive system of male offspring mice.

Prochloraz is a widely used fungicide worldwide. It is classified as an endocrine disrupting pesticide that affects the reproductive system. This study aimed to examine the impact of exposure to prochloraz of male mice on the reproductive system of their offspring male mice. Male father mice were intragastrically administered different dosages of prochloraz (group MA: 0 mg/kg/day; MB: 53.33 mg/kg/day; MD:160 mg/kg/day). Then, the testicular average weight of male offspring in the dose groups was found to be significantly lower than those in the control group (MB:0.312g, MD:0.294g, and MA:0.355 g; P < 0.05). Additionally, the testicular coefficient index in the MB and MD groups was also lower than that of the control group. Secondly,we observed that there were significantly different expressed genes clustered in groups B and D, in contrast to the control. Finally, the findings demonstrated a significant alteration in the response of male mice reproductive relative genes to prochloraz invasion. Two genes (Mt-nd6 and Slc12a4) were found to be involved in the regulation of sperm mitochondria function and six genes (Greb1, Esrrb, Catsperb, Mospd2, Sohlh1 and Specc1) were closely linked to sperm functions and estrogen response. The study revealed a significant impact of prochloraz on the reproductive system of male mice, thereby supporting further investigation into the reproductive toxicological effects of the drug.