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VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources. Results indicated that the TVOCs (total VOCs) concentration was (96.7 ± 63.4 µg/m3), with alkanes exhibiting the highest concentration of (36.1 ± 26.4 µg/m3), followed by OVOCs (16.4 ± 14.4 µg/m3). The key active components were alkenes and aromatics, among which xylene, propylene, toluene, propionaldehyde, acetaldehyde, ethylene, and styrene played crucial roles as reactive species. The sources derived from PMF analysis encompassed vehicle emissions, solvent and coating sources, combustion sources, industrial emissions sources, as well as plant sources, the contribution of which were 37.80%, 27.93%, 16.57%, 15.24%, and 2.46%, respectively. Hence, reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.

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Agricultural practices significantly contribute to greenhouse gas (GHG) emissions, necessitating cleaner production technologies to reduce environmental pressure and achieve sustainable maize production. Plastic film mulching is commonly used in the Loess Plateau region. Incorporating slow-release fertilizers as a replacement for urea within this practice can reduce nitrogen losses and enhance crop productivity. Combining these techniques represents a novel agricultural approach in semi-arid areas. However, the impact of this integration on soil carbon storage (SOCS), carbon footprint (CF), and economic benefits has received limited research attention. Therefore, we conducted an eight-year study (2015-2022) in the semi-arid northwestern region to quantify the effects of four treatments [urea supplied without plastic film mulching (CK-U), slow-release fertilizer supplied without plastic film mulching (CK-S), urea supplied with plastic film mulching (PM-U), and slow-release fertilizer supplied with plastic film mulching (PM-S)] on soil fertility, economic and environmental benefits. The results revealed that nitrogen fertilizer was the primary contributor to total GHG emissions (≥71.97%). Compared to other treatments, PM-S increased average grain yield by 12.01%-37.89%, water use efficiency by 9.19%-23.33%, nitrogen accumulation by 27.07%-66.19%, and net return by 6.21%-29.57%. Furthermore, PM-S decreased CF by 12.87%-44.31% and CF per net return by 14.25%-41.16%. After eight years, PM-S increased SOCS (0-40 cm) by 2.46%, while PM-U decreased it by 7.09%. These findings highlight the positive effects of PM-S on surface soil fertility, economic gains, and environmental benefits in spring maize production on the Loess Plateau, underscoring its potential for widespread adoption and application.

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Purpose: Drug-induced gynecomastia significantly affects patient health and quality of life. This study aimed to perform an exploratory analysis of gynecomastia reports and the most commonly associated medications within the FAERS database. Patients and Methods: A comprehensive analysis of the FAERS from January 2004 to December 2023 was conducted. Disproportionality analysis and subsequent sensitivity analysis were performed to identify drugs potentially associated with gynecomastia, utilizing the reported odds ratio (ROR). Logistic regression analysis was employed to assess potential risk factors. The Weibull shape parameter (WSP) test was used to assess the time-to-onset characteristics of the top drugs associated with gynecomastia. Results: The study identified 30,265 cases of gynecomastia, primarily associated with nervous system drugs, accounting for 85.50% of cases. Notably, risperidone accounted for 80.81% of the total cases. Among the 165 agents with ≥ 5 cases of gynecomastia, the strongest signals were exhibited by risperidone (ROR 602.38, 95% CI 585.07-620.20), dutasteride (ROR 17.18, 95% CI 15.55-18.89), spironolactone (ROR 15.8, 95% CI 13.99-17.83), and paliperidone (ROR 7.16, 95% CI 6.55-7.84). In the sensitivity analysis of disproportionality, unexpected associations were observed, such as montelukast (n = 21, ROR 1.94, 95% CI 1.26-2.98). The logistic regression analysis indicated that the risk of risperidone-induced gynecomastia was significantly lower in adults compared to pediatric patients (OR 0.12, 95% CI 0.09-0.15) and in patients with higher body weight than in those with lower body weight (OR 5.24, 95% CI 3.62-7.76). The WSP test showed that gynecomastia induced by most of the top 10 common agents tends to occur in an early failure mode. Conclusion: The rankings and signal strengths of drugs associated with gynecomastia were extracted from the FAERS. The age distribution and time-to-onset distribution of the top 10 drugs linked to gynecomastia were investigated, which can facilitate accurate clinical recognition of drug-induced gynecomastia.

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Erythropoietin-producing hepatocyte receptor A2 (EphA2) is an attractive target for immunotherapy due to its high expression in a variety of solid tumors including prostate cancer. Among various types of immunotherapeutics, chimeric antigen receptor T (CAR-T) cell therapy has made promising progress in hematological and solid tumors. Here, we detected the expression of EphA2 in prostate cancer cells and developed a second-generation CAR targeting EphA2 with CD28 as a co-stimulatory receptor to explore its tumor suppressive potential for prostate cancer in vitro and in vivo. EphA2 was highly expressed on the surface of PC3 and DU145 cells. EphA2 CART cells effectively inhibited prostate cancer growth in an antigen-dependent manner in vitro and in vivo. In addition, tumor cells could stimulate the proliferation of CAR-T cells and the release of cytokine IFN-γ in vitro. These findings shed light on EphA2 as a potential target for prostate cancer, promising EphA2 specific CAR-T cells for the treatment of prostate cancer.

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The practical application of aqueous zinc ion batteries is still hampered by the side reactions and dendrite growth on Zn anode. Herein, phase engineering of ZnSe coating layer by incorporating small molecules is developed to enhance the performance of Zn anode. The unique electronic structure of ZnSe·0.5N2H4 promises strong adsorption for Zn atoms and enhanced ability to inhibit hydrogen evolution, thereby promoting uniform Zn deposition and preventing by-product and dendrite growth. Meanwhile, fast Zn2+ transfer and deposition kinetics are also demonstrated by ZnSe·0.5N2H4. As a result, the ZnSe·0.5N2H4@Zn symmetric cell achieves long-term cycling stability up to 1900 h and 300 h at high current densities of 5 mA cm-2 and 20 mA cm-2, respectively. The assembled ZnSe·0.5N2H4@Zn||NVO full cell presents outstanding cycling stability and rate capability. This work highlights the key role of crystal phase control of protective layer for high-performance zinc anode.

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The type VI secretion system 2 (T6SS2) gene cluster of Vibrio parahaemolyticus comprises three operons: VPA1027-1024, VPA1043-1028, and VPA1044-1046. AcsS is a LysR-like transcriptional regulator that play a role in activating flagella-driven motility in V. parahaemolyticus. However, its potential roles in other cellular pathways remain poorly understood. In this study, we conducted a series of experiments to investigate the regulatory effects of AcsS on the transcription of VPA1027 (hcp2), VPA1043, and VPA1044. The findings revealed that AcsS indirectly inhibits the transcription of these genes. Additionally, deletion of acsS resulted in enhanced adhesion of V. parahaemolyticus to HeLa cells. However, disruption of T6SS2 alone or in conjunction with AcsS significantly diminished the adhesion capacity of V. parahaemolyticus to HeLa cells. Therefore, it is suggested that AcsS suppresses cell adhesion in V. parahaemolyticus by downregulating the transcription of T6SS2 genes.

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BACKGROUND: To explore the risk factors of proteinuria in Omicron variant patients and to construct and verify the risk predictive model. METHODS: 1091 Omicron patients who were hospitalized from August 2022 to November 2022 at Tianjin First Central Hospital were defined as the derivation cohort. 306 Omicron patients who were hospitalized from January 2022 to March 2022 at the same hospital were defined as the validation cohort. The risk factors of proteinuria in derivation cohort were screened by univariate and multivariate logistic regression analysis, and proteinuria predicting scoring system was constructed and the receiver operating characteristic(ROC)curve was drawn to test the prediction ability. The proteinuria risk model was externally validated in validation cohort. RESULTS: 7 factors including comorbidities, blood urea nitrogen (BUN), serum sodium (Na), uric acid (UA), C reactive protein (CRP) and vaccine dosages were included to construct a risk predictive model. The score ranged from -5 to 16. The area under the ROC curve(AUC) of the model was 0.8326(95% CI 0.7816 to 0.8835, p < 0.0001). Similarly to that observed in derivation cohort, the AUC is 0.833(95% CI 0.7808 to 0.9002, p < 0.0001), which verified good prediction ability and diagnostic accuracy in validation cohort. CONCLUSIONS: The risk model of proteinuria after Omicron infection had better assessing efficiency which could provide reference for clinical prediction of the risk of proteinuria in Omicron patients.

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Our previous study has verified that activation of group Ⅰ metabotropic glutamate receptors (mGluRⅠ) in the red nucleus (RN) facilitate the development of neuropathological pain. Here, we further discussed the functions and possible molecular mechanisms of red nucleus mGluR Ⅱ (mGluR2 and mGluR3) in the development of neuropathological pain induced by spared nerve injury (SNI). Our results showed that mGluR2 and mGluR3 both were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the protein expression of mGluR2 rather than mGluR3 was significantly reduced in the RN contralateral to the nerve lesion. Injection of mGluR2/3 agonist LY379268 into the RN contralateral to the nerve injury at 2 weeks post-SNI significantly attenuated SNI-induced neuropathological pain, this effect was reversed by mGluR2/3 antagonist EGLU instead of selective mGluR3 antagonist ß-NAAG. Intrarubral injection of LY379268 did not alter the PWT of contralateral hindpaw in normal rats, while intrarubral injection of EGLU rather than ß-NAAG provoked a significant mechanical allodynia. Further studies indicated that the expressions of nociceptive factors TNF-α and IL-1ß in the RN were enhanced at 2 weeks post-SNI. Intrarubral injection of LY379268 at 2 weeks post-SNI significantly suppressed the overexpressions of TNF-α and IL-1ß, these effects were reversed by EGLU instead of ß-NAAG. Intrarubral injection of LY379268 did not influence the protein expressions of TNF-α and IL-1ß in normal rats, while intrarubral injection of EGLU rather than ß-NAAG significantly boosted the expressions of TNF-α and IL-1ß. These findings suggest that red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1ß. mGluR Ⅱ may be potential targets for drug development and clinical treatment of neuropathological pain.

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Dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (dFDG-PET) for human brain imaging has considerable clinical potential, yet its utilization remains limited. A key challenge in the quantitative analysis of dFDG-PET is characterizing a patient-specific blood input function, traditionally reliant on invasive arterial blood sampling. This research introduces a novel approach employing non-invasive deep learning model-based computations from the internal carotid arteries (ICA) with partial volume (PV) corrections, thereby eliminating the need for invasive arterial sampling. We present an end-to-end pipeline incorporating a 3D U-Net based ICA-net for ICA segmentation, alongside a Recurrent Neural Network (RNN) based MCIF-net for the derivation of a model-corrected blood input function (MCIF) with PV corrections. The developed 3D U-Net and RNN was trained and validated using a 5-fold cross-validation approach on 50 human brain FDG PET scans. The ICA-net achieved an average Dice score of 82.18% and an Intersection over Union of 68.54% across all tested scans. Furthermore, the MCIF-net exhibited a minimal root mean squared error of 0.0052. The application of this pipeline to ground truth data for dFDG-PET brain scans resulted in the precise localization of seizure onset regions, which contributed to a successful clinical outcome, with the patient achieving a seizure-free state after treatment. These results underscore the efficacy of the ICA-net and MCIF-net deep learning pipeline in learning the ICA structure's distribution and automating MCIF computation with PV corrections. This advancement marks a significant leap in non-invasive neuroimaging.

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Achieving a desired whitening effect through short treatments without using peroxide and without compromising the integrity of tooth enamel remains a challenge in teeth whitening. Here, we developed a highly safe and efficient photodynamic therapy (PDT) strategy based on visible light-activated bismuth oxyiodide nanoparticles for nondestructive tooth whitening. The Bi7O9I3 nanoparticles (NPs) exhibited efficient photocatalytic activity owing to their narrow band gap, effectively harnessing the broad spectrum of visible light to generate ample electrons and holes. Meanwhile, the presence of oxygen vacancies, low oxidation state Bi3+ and the high specific surface area endow Bi7O9I3 NPs with effective electron-hole separation ability and potent redox potentials. Empowered by these characteristics, Bi7O9I3 NPs effectively catalyzed O2 into radicals (O2•-), facilitating the degradation of dental surface pigment molecules for tooth whitening. Concurrently, they eradicated oral bacteria and bacterial biofilms adhering to tooth surfaces, thereby having a positive effect on the effectiveness of tooth whitening. This PDT strategy with Bi7O9I3 NPs shows broad application prospects in tooth whitening.

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Cyclic di-GMP (c-di-GMP), a ubiquitous secondary messenger in bacteria, affects multiple bacterial behaviors including motility and biofilm formation. c-di-GMP is synthesized by diguanylate cyclase harboring a GGDEF domain and degraded by phosphodiesterase harboring an either EAL or HD-GYP domain. Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, harbors more than 60 genes involved in c-di-GMP metabolism. However, roles of most of these genes including vpa0198, which encodes a GGDEF-domain containing protein, are still completely unknown. AphA and OpaR are the master quorum sensing (QS) regulators operating at low (LCD) and high cell density (HCD), respectively. QsvR integrates into QS to control gene expression via direct regulation of AphA and OpaR. In this study, we showed that deletion of vpa0198 remarkably reduced c-di-GMP production and biofilm formation, whereas promoted the swimming motility of V. parahaemolyticus. Overexpression of VPA0198 in the vpa0198 mutant strain significantly reduced the swimming and swarming motility and enhanced the biofilm formation ability of V. parahaemolyticus. In addition, transcription of vpa0198 was under the collective regulation of AphA, OpaR and QsvR. AphA activated the transcription of vpa0198 at LCD, whereas QsvR and OpaR coordinately and directly repressed vpa0198 transcription at HCD, thereby leading to a cell density-dependent expression of vpa0198. Therefore, this work expanded the knowledge of synthetic regulatory mechanism of c-di-GMP in V. parahaemolyticus.

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RATIONALE: As one of the drugs used to treat Helicobacter pylori, furazolidone has been reported to cause gastrointestinal reactions, allergies, dizziness, and more. However, its related drug-induced lung injury has been rarely reported. Furthermore, there have been no reports of the timing for initiating hormone therapy when a pulmonary adverse reaction occurs. PATIENT CONCERNS: We report 2 cases, both of them showed interlobular septal thickening and nodules on the chest computed tomography. One had more discomfort symptoms and had a higher eosinophil count than the normal range, while the other only had fever symptoms and had an eosinophil count within the normal range. DIAGNOSES: Pulmonary adverse reaction caused by furazolidone was diagnosed. INTERVENTIONS: Furazolidone was discontinued, and the person with increased eosinophils received hormone therapy, while the other person did not. OUTCOMES: After discontinuation of medication and treatment, the symptoms of the 2 patients gradually improved. LESSONS: This report suggests that furazolidone may cause pulmonary adverse reactions to raise clinical awareness, and for the first time indicates that hormone therapy is needed for patients whose eosinophils continue to increase after discontinuation.

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Vanillin is an inhibitor of lignocellulose hydrolysate, which can reduce the ability of Saccharomyces cerevisiae to utilize lignocellulose, which is an important factor limiting the development of the ethanol fermentation industry. In this study, mutants of vanillin-tolerant yeast named H6, H7, X3, and X8 were bred by heavy ion irradiation (HIR) combined with adaptive laboratory evolution (ALE). Phenotypic tests revealed that the mutants outperformed the original strain WT in tolerance, growth rate, genetic stability and fermentation ability. At 1.6 g/L vanillin concentration, the average OD600 value obtained for mutant strains was 0.95 and thus about 3.4-fold higher than for the wild-type. When the concentration of vanillin was 2.0 g/L, the glucose utilization rate of the mutant was 86.3 % within 96 h, while that of the original strain was only 70.0 %. At this concentration of vanillin, the mitochondrial membrane potential of the mutant strain recovered faster than that of the original strain, and the ROS scavenging ability was stronger. We analyzed the whole transcriptome sequencing map and the whole genome resequencing of the mutant, and found that DEGs such as FLO9, GRC3, PSP2 and SWF1, which have large differential expression multiples and obvious mutation characteristics, play an important role in cell flocculation, rDNA transcription, inhibition of DNA polymerase mutation and protein palmitoylation. These functions can help cells resist vanillin stress. The results show that combining HIR with ALE is an effective mutagenesis strategy. This approach can efficiently obtain Saccharomyces cerevisiae mutants with improved vanillin tolerance, and provide reference for obtaining robust yeast strains with lignocellulose inhibitor tolerance.

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Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the outbreak of COVID-19 in Wuhan, China. As a highly infectious epidemic, SARS-CoV-2 rapidly evolves. Presently, COVID-19 coexists with humans, mainly with mild or moderate disease. The latest Guidelines for the Diagnosis and Treatment of COVID-19 (trial version of the 10th Edition) recommend several oral traditional Chinese medicines (TCMs) for treatment. This study aims to evaluate the evidence-based benefits of these TCMs as adjunctive therapies to conventional western medicine (CWM) for patients with mild or moderate COVID-19. Methods: We conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the PRISMA checklist. We searched PubMed, Cochrane Library, Embase, CNKI, and Wan-Fang databases to retrieve randomized controlled trials and retrospective cohort studies of TCM in combination with CWM on the treatment of mild or moderate COVID-19 that were published as of December 25, 2023. A network meta-analysis using the frequency model was employed to evaluate the benefits of different interventions. Results: A total of 30 eligible studies, enrolling 4144 participants, utilized 7 marketed oral TCMs in China. Compared with CWM alone, the integration of TCMs with CWM can significantly reduce severe conversion rate. This combined approach also enhances the clinical effective rate, shortens the negative conversion time of nucleic acid, and improves both symptoms and blood biochemical markers in patients. The network meta-analysis provided preliminary evidence of the superiority of specific TCMs for various outcomes: Qingfei Paidu for raising the CT improvement rate and clinical effective rate, and shortening the negative conversion time of nucleic acid; Huashi Baidu for reducing severe conversion and improving cough; Xuanfei Baidu for improving fatigue; Jinhua Qinggan for improving fever; Lianhua Qingwen for shortening the recovery time of fatigue and cough; and Shufeng Jiedu for shortening the recovery time of fever. Conclusions: TCM in combination with CWM may be beneficial for patients with mild or moderate COVID-19. Each TCM may have distinct benefits in COVID-19.

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Introduction: Traditional/ritual/medical circumcision can be associated with considerable intraoperative blood loss and a prolonged postoperative healing course. This study investigated the feasibility of the magnetic compression technique (MCT) for circumcision in beagle dogs. Methods: A set of magnetic rings including a daughter magnetic ring (DMR) and a parent magnetic ring (PMR) were designed for circumcision. In eight beagle dogs as the animal model, the DMR was placed between the penis and the foreskin through the glans, and then the PMR was placed outside the penis. The DMR and PMR automatically attracted together to compress the foreskin. The necrosis of the prepuce of the anterior penis was observed daily. The operation time and time to magnetic ring shedding were recorded. Healing of the foreskin stump was visually observed. Results: The magnetic rings were successfully installed in all eight dogs, and the operation process was without complication. The average operation time was 3.13 ± 0.92 min (range, 2-4.5 min). Postoperative X-rays showed good attraction of the magnetic rings. Daily post-operative observation showed progressive ischemic necrosis of the anterior foreskin and mild edema of the proximal foreskin. The dogs were generally in good condition and urinated freely. The magnetic rings fell off spontaneously 8-12 days after the operation, and the stump of the foreskin healed well. Conclusion: The MCT may be a new approach for circumcision in a canine model, which suggests its potential for use in humans.

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The aim of this study was to investigate the prevalence of Vibrionaceae family in retail seafood products available in the Qidong market during the summer of 2023 and to characterize Vibrio parahaemolyticus isolates, given that this bacterium is the leading cause of seafood-associated food poisoning. We successfully isolated a total of 240 Vibrionaceae strains from a pool of 718 seafood samples. The breakdown of the isolates included 146 Photobacterium damselae, 59 V. parahaemolyticus, 18 V. campbellii, and 11 V. alginolyticus. Among these, P. damselae and V. parahaemolyticus were the predominant species, with respective prevalence rates of 20.3% and 8.2%. Interestingly, all 59 isolates of V. parahaemolyticus were identified as non-pathogenic. They demonstrated proficiency in swimming and swarming motility and were capable of forming biofilms across a range of temperatures. In terms of antibiotic resistance, the V. parahaemolyticus isolates showed high resistance to ampicillin, intermediate resistance to cefuroxime and cefazolin, and were sensitive to the other antibiotics evaluated. The findings of this study may offer valuable insights and theoretical support for enhancing seafood safety measures in Qidong City.

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BACKGROUND: Lignocellulose is a renewable and sustainable resource used to produce second-generation biofuel ethanol to cope with the resource and energy crisis. Furfural is the most toxic inhibitor of Saccharomyces cerevisiae cells produced during lignocellulose treatment, and can reduce the ability of S. cerevisiae to utilize lignocellulose, resulting in low bioethanol yield. In this study, multiple rounds of progressive ionizing radiation was combined with adaptive laboratory evolution to improve the furfural tolerance of S. cerevisiae and increase the yield of ethanol. RESULTS: In this study, the strategy of multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution significantly improved the furfural tolerance of brewing yeast. After four rounds of experiments, four mutant strains resistant to high concentrations of furfural were obtained (SCF-R1, SCF-R2, SCF-R3, and SCF-R4), with furfural tolerance concentrations of 4.0, 4.2, 4.4, and 4.5 g/L, respectively. Among them, the mutant strain SCF-R4 obtained in the fourth round of radiation had a cellular malondialdehyde content of 49.11 nmol/mg after 3 h of furfural stress, a weakening trend in mitochondrial membrane potential collapse, a decrease in accumulated reactive oxygen species, and a cell death rate of 12.60%, showing better cell membrane integrity, stable mitochondrial function, and an improved ability to limit reactive oxygen species production compared to the other mutant strains and the wild-type strain. In a fermentation medium containing 3.5 g/L furfural, the growth lag phase of the SCF-R4 mutant strain was shortened, and its growth ability significantly improved. After 96 h of fermentation, the ethanol production of the mutant strain SCF-R4 was 1.86 times that of the wild-type, indicating that with an increase in the number of irradiation rounds, the furfural tolerance of the mutant strain SCF-R4 was effectively enhanced. In addition, through genome-transcriptome analysis, potential sites related to furfural detoxification were identified, including GAL7, MAE1, PDC6, HXT1, AUS1, and TPK3. CONCLUSIONS: These results indicate that multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution is an effective mutagenic strategy for obtaining furfural-tolerant mutants and that it has the potential to tap genes related to the furfural detoxification mechanism.

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Background: The global prevalence of infertility is 9%, with male factors potentially accounting for 40% to 60% of cases. Conventional treatments can be ineffective, invasive, costly, and linked to adverse effects and high risks. Previous studies have shown that, Chinese herbal medicine (CHM) can regulate the hypothalamus-pituitary-testis axis, improve sperm abnormalities and quality, mitigate oxidative stress, and decrease DNA fragmentation index (DFI). Yet, the evidence backing the use of Chinese herbal medicine (CHM) for treating male factor infertility lacks conviction due to study design limitations, and there remains a scarcity of studies on the live birth rate following CHM treatment for male factor infertility. Here, we describe the rationale and design of a randomized waitlist-controlled trial to evaluate the effect of CHM on the live birth rate among males with infertility. Methods: This study is a single-center, randomized, waitlist-controlled study. A total of 250 couples diagnosed with male factor infertility will be enrolled in this study and then randomly allocated into two groups in a 1:1 ratio. Male participants in CHM group (treatment group) will receive CHM once a day for 3 months. Male participants in the waitlist group (control group) will not receive any treatment for 3 months. After 3 months, participants in both groups need to be followed up for another 12 months. The primary outcome will be the live birth rate; secondary outcomes include semen quality parameters, DFI and pregnancy related outcomes. Safety will also be assessed. Discussion: The purpose of this trial is to explore the effects and safety of CHM on the live birth rate among couples dealing with male factor infertility. The outcome of this trial may provide a viable treatment option for male factor infertility. Trial registration: Chinese Clinical Trial Registry: ChiCTR2200064416. Registered on 7 October 2022, https://www.chictr.org.cn.

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The pathogenesis of rheumatoid arthritis (RA) remains elusive. The initiation of joint degeneration is characterized by the loss of self-tolerance in peripheral joints. Ferroptosis, a form of regulated cell death, holds significant importance in the pathophysiology of inflammatory arthritis, primarily due to iron accumulation and the subsequent lipid peroxidation. The present study investigated the association between synovial lesions and ferroptosis-related genes using previously published data from rheumatoid patients. Transcriptome differential gene analysis was employed to identify ferroptosis-related differentially expressed genes (FRDEGs). To validate FRDEGs and screen hub genes, we used weighted gene co-expression network analysis (WGCNA) and receiver operating characteristic (ROC) curves. Subsequently, immune infiltration analysis and single cell analysis were conducted to investigate the relationship between various synovial tissues cells and FRDEGs. The findings were further confirmed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemical staining, and immunofluorescence techniques. Upon intersecting DEGs with ferroptosis-related genes, we identified a total of 104 FRDEGs. Through the construction of a protein-protein interaction (PPI) network, we pinpointed the top 20 most highly concentrated genes as hub genes. Subsequent analyses using ROC curve and WGCNA validated eight FRDEGs: TIMP1, JUN, EGFR, SREBF1, ADIPOQ, SCD, AR, and FABP4. Immuno-infiltration analyses revealed significant infiltration of immune cell in RA synovial tissues and their correlations with the FRDEGs. Notably, TIMP1 demonstrated a positive correlation with various immune cell populations. Single-cell sequencing date of RA synovial tissue revealed predominant expression of TIMP1 is in fibroblasts. RT-qPCR, immunohistochemistry, and immunofluorescence analyses confirmed significant upregulation of TIMP1 at both mRNA and protein levels in RA synovial tissues and fibroblast-like synoviocytes (FLS). The findings provide novel insights into pathophysiology of peripheral immune tolerance deficiency in RA. The dysregulation of TIMP1, a gene associated with ferroptosis, was significantly observed in RA patients, suggesting its potential as a promising biomarker and therapeutic target.