Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.

The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.

Multi-Scale Feature Fusion Network for Low-Dose CT Denoising.

Computed tomography (CT) is an imaging technique extensively used in medical treatment, but too much radiation dose in a CT scan will cause harm to the human body. Decreasing the dose of radiation will result in increased noise and artifacts in the reconstructed image, blurring the internal tissue and edge details. To get high-quality CT images, we present a multi-scale feature fusion network (MSFLNet) for low-dose CT (LDCT) denoising. In our MSFLNet, we combined multiple feature extraction modules, effective noise reduction modules, and fusion modules constructed using the attention mechanism to construct a horizontally connected multi-scale structure as the overall architecture of the network, which is used to construct different levels of feature maps at all scales. We innovatively define a composite loss function composed of pixel-level loss based on MS-SSIM-L1 and edge-based edge loss for LDCT denoising. In short, our approach learns a rich set of features that combine contextual information from multiple scales while maintaining the spatial details of denoised CT images. Our laboratory results indicate that compared with the existing methods, the peak signal-to-noise ratio (PSNR) value of CT images of the AAPM dataset processed by the new model is 33.6490, and the structural similarity (SSIM) value is 0.9174, which also achieves good results on the Piglet dataset with different doses. The results also show that the method removes noise and artifacts while effectively preserving CT images' architecture and grain information.

Edge feature extraction-based dual CNN for LDCT denoising.

In low-dose computed tomography (LDCT) denoising tasks, it is often difficult to balance edge/detail preservation and noise/artifact reduction. To solve this problem, we propose a dual convolutional neural network (CNN) based on edge feature extraction (Ed-DuCNN) for LDCT. Ed-DuCNN consists of two branches. One branch is the edge feature extraction subnet (Edge_Net) that can fully extract the edge details in the image. The other branch is the feature fusion subnet (Fusion_Net) that introduces an attention mechanism to fuse edge features and noisy image features. Specifically, first, shallow edge-specific detail features are extracted by trainable Sobel convolutional blocks and then are integrated into Edge_Net together with the LDCT images to obtain deep edge detail features. Finally, the input image, shallow edge detail, and deep edge detail features are fused in Fusion_Net to generate the final denoised image. The experimental results show that the proposed Ed-DuCNN can achieve competitive performance in terms of quantitative metrics and visual perceptual quality compared with that of state-of-the-art methods.

Association between generalized anxiety symptoms and semen quality in infertile men: A multicentre study in North China.

This study was conducted to investigate the generalized anxiety levels and its association with semen quality in infertile men. We recruited male patients who visited the infertility outpatient departments of three teaching hospitals in North China and evaluated their generalized anxiety symptoms using the self-administered 7-item generalized anxiety disorder (GAD-7) scale. Seminal analysis was performed as per WHO guidelines. A total of 378 infertile men (average age: 31.43 ± 5.85 years) were classified into the normal group (n = 174, 46%) and the anxiety group (n = 204, 54%) according to their GAD-7 scale score. The proportion of patients with hyperlipidaemia in the normal group was significantly higher than that in the anxiety group (14.9% vs. 5.9%, p = 0.004). The other demographic characteristics were not statistically different between both groups. Patients with abnormal GAD-7 scale scores had a significantly lower sperm count (202.48 vs. 166.80 million per ejaculate, p = 0.023), sperm concentration (54.75 vs. 46.54 million/ml, p = 0.033), and progressive motility (40.25 vs. 37.16, p = 0.020) than those with normal GAD-7 scale scores. Multivariate linear regression models revealed that anxiety was significantly negatively associated with sperm concentration (percent change = -9.79, 95%CI: -12.38 to -7.12, p < 0.001), total sperm count (percent change = -13.07, 95%CI: -16.05 to -9.84, p < 0.001), progressive motility (ß = -1.41, 95%CI: -1.86 to -0.96, p < 0.001), total sperm motility (ß = -1.73, 95%CI: -2.38 to -1.08, p < 0.001), and normal sperm morphology (ß = -0.16, 95%CI: -0.28 to -0.04, p = 0.009), respectively. Taken together, generalized anxiety disorder could significantly influence the clinical semen quality in infertile men in North China, and psychological stress management might be helpful.

A study of diabetes-induced erectile dysfunction treated with human umbilical cord mesenchymal stem cells.

The present study aimed to assess the value of human umbilical cord mesenchymal stem cells (hUC-MSCs) for the treatment of diabetes-induced erectile dysfunction (DMED). We established a type 1 diabetes model through intra-abdominal streptozotocin injection. After 10 weeks, an apomorphine test was performed to screen the rats for erectile dysfunction (ED). The rats were divided into three groups: normal control group (n = 10), DMED group (n = 9) and DMED+hUC-MSC group (n = 9). After 4 weeks of hUC-MSC therapy, erectile function was evaluated by intracavernous pressure measurements, and penile tissue collagen and smooth muscle were examined by haematoxylin-eosin and Masson's trichrome staining. In addition, western blotting, immunohistochemistry and RT-PCR analysis of TLR4, VEGF and eNOS were performed. The results showed that hUC-MSC treatment restored erectile function (p < .05) and reversed the smooth muscle/collagen ratio changes of DMED rats (p < .05). Furthermore, hUC-MSC treatment inhibited the expression of TLR4 (p < .05) and enhanced VEGF and eNOS expression (p < .05). In conclusion, hUC-MSC treatment restored the erectile function of diabetic rats by inhibiting TLR4, improving corpora cavernosa fibrosis, and increasing VEGF and eNOS expression.

Low-dose CT noise reduction based on local total variation and improved wavelet residual CNN.

BACKGROUND: Low-dose computed tomography (LDCT) is an effective method for reducing radiation exposure. However, reducing radiation dose leads to considerable noise in the reconstructed image that can affect doctor's judgment. OBJECTIVE: To solve this problem, this study proposes a local total variation and improved wavelet residual convolutional neural network (LTV-WRCNN) denoising model. METHODS: The model first introduces local total variation (LTV) to decompose the LDCT image into cartoon and texture image. Next, the texture image is filtered using the non-local mean (NLM). Then, the cartoon image is added to the filtered texture image to obtain the preprocessing image. Finally, the pre-processed image is fed into the improved wavelet residual neural network (WRCNN) to obtain an improved image. Additionally, we also introduce a compound loss in wavelet domain that combines mean squared error loss and directional regularization loss to separate the structural details from noise more thoroughly. RESULTS: Compared with state-of-the-art methods, the peak-signal-to-noise ratio (PSNR) value and the structure similarity (SSIM) value of the processed CT images using the new proposed model are 33.4229 dB and 0.9158. Study also shows that applying new model obtains better results visually and numerically, especially in terms of the preservation of structural details. CONCLUSIONS: The proposed new model is feasible and effective in improving the quality of LDCT images.

The association between anogenital distance and benign prostatic hyperplasia related lower urinary tract symptoms in Chinese aging men.

PURPOSE: We conducted the study to investigate the relationship between anogenital distance (AGD) and benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). METHODS: From May 2018 to January 2020, 220 subjects: 110 men with BPH-related LUTS (BPH-LUTS group) and 110 men without any urination complaints (control group) were selected. Clinical questionnaires, detailed physical examinations, including AGDas (distance between the anus and posterior base of the scrotum) and AGDap (distance between the anus and upper penis) measurements, and blood tests were all assessed. RESULTS: The two groups were similar in terms of basic features (P > 0.05). The AGDap and AGDas in the control group were significantly shorter than the BPH-LUTS group (P < 0.001). Adjusted multivariate analyses showed that AGDas was significantly related to International Prostate Symptom Score (IPSS), post-voiding residual volume (PVR), total prostate volume (TPV) and maximum urine flow rate (Qmax) (P = 0.002, P = 0.009, P = 0.001, P = 0.028, respectively). However, the associations between AGDap and IPSS score, PVR, TPV, Qmax and total testosterone (TT) were all negligible (P > 0.05 for all). The associations between TT and BPH-LUTS related evaluations were also negligible (P > 0.05 for all). Furthermore, the study revealed that the AGDas cut-off values for mild, moderate, and severe symptom (based on IPSS score) in BPH-LUTS cases were 27.4 mm and 46.8 mm [area under curve (AUC): 0.802 and AUC: 0.779, respectively], respectively. CONCLUSION: Longer AGDas was related to more severe BPH related symptoms. It may be useful to consider AGD as a marker for BPH-LUTS. Further well-designed studies are remained to be done to explore the intriguing problem.

Association between human papillomavirus infection and sperm quality: A systematic review and a meta-analysis.

Human papillomavirus (HPV) has a high incidence rate in both males and females. HPV infection in women has been shown to affect fertility and lead to foetal death and pregnancy loss. However, research on HPV infection in men is limited. The aim of this study was to study the effect of HPV infection in semen on sperm quality and present the findings of previous studies through a meta-analysis. Databases including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, WanFang data and China National Knowledge Infrastructure were searched for relevant studies. A systematic review and meta-analysis were performed, and 17 studies were included for analyses based on a set criterion. Meta-analyses indicated that HPV infection in semen significantly reduced sperm concentration (SMD = -0.12, 95% CI: -0.21 to -0.03, p = .009), sperm motility (SMD = -0.55, 95% CI: -0.780 to -0.33, p = .000), sperm viability (SMD = -0.55, 95% CI: -0.780 to -0.33, p = .000) and sperm morphology (SMD = -0.34, 95% CI: -0.61 to -0.07, p = .015). The high-risk HPV (HrHPV) infection could significantly reduce sperm count (SMD = -0.65, 95% CI: -1.11 to -0.18, p = .007) compared with high-risk HPV (LrHPV) infection. In conclusion, HPV infection in semen significantly reduced sperm quality, and the HrHPV infection could significantly reduce sperm count compared with LrHPV.

Identification of new biomarkers in immune microenvironment of testicular germ cell tumour.

To seek novel prognostic biomarkers for testicular germ cell tumour (TGCT) and investigate the tumour immune microenvironment, we identified critical differentially expressed genes (DEGs) by overlapping GSE1818 dataset from Gene Expression Omnibus (GEO). Protein-protein interaction (PPI) network was used to investigate key modules and hub genes. Functional enrichment analysis was performed to investigate the underlying molecular functions of the DEGs in TGCT development and progression. The following survival analysis based on The Cancer Genome Atlas (TCGA) TGCT dataset indicated that AKAP4, SPA17 and TNP1 are correlated with TGCT prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction verified the down-regulation of the 3 hub genes in TGCT. Gene set enrichment analysis was conducted to further explore the role of the 3 hub genes in TGCT respectively. In addition, TGCT samples had high infiltration of CD8+ T cells, M0 and M1 macrophage cells, and resting myeloid dendritic cells in immune microenvironment. We also constructed the microRNA-gene regulatory networks to identify the key upstream microRNAs in TGCT. In conclusion, our findings indicated that AKAP4, SPA17 and TNP1 are promising biomarkers of TGCT. AKAP4 and TNP1 might regulate immune cells infiltration in immune microenvironment.

Identification of key genes in type 2 diabetes-induced erectile dysfunction rats with stem cell therapy through high-throughput sequencing and bioinformatic analysis.

Diabetes mellitus erectile dysfunction (DMED) is a frequent complication of diabetes. Mesenchymal stem cell (MSC) therapy was demonstrated to improve erectile function in DMED. However, the pathogenesis of DMED and the mechanism by which MSCs function are still unclear. We established a rat model of DMED and gave MSC therapy through intracavernous injection. After transcriptome sequencing of rats' penile tissue, we identified a total of 1,097 overlapped differentially expressed genes (DEGs) of the normal control group, DMED group, and MSC-treated group, containing 189 upregulated genes and 908 downregulated genes. The enriched functions of upregulated DEGs included extracellular matrix organisation (GO:0030198), extracellular structure organisation (GO:0043062), and wound healing (GO:0042060), PPAR signalling pathway (rno03320), arachidonic acid metabolism (rno00590) and retinol metabolism (rno00830). The enriched functions of downregulated DEGs included peptidase activity (GO:0052547), hair follicle development (GO:0001942), intermediate filament-based process (GO:0045103), nitrogen metabolism (rno00910), aldosterone-regulated sodium reabsorption (rno04960) and retinol metabolism (rno00830). We constructed a PPI network with 547 nodes and 2,365 edges and identified 15 hub genes with high connectivity degree. In summary, 15 hub genes with potential roles in the development of ED were identified. Further functional research would be required to elucidate the molecular mechanism underlying misregulated genes.

Inhibition of inducible nitric oxide synthase improved erectile dysfunction in rats with type 1 diabetes.

Diabetes mellitus (DM), which is closely related to microvascular dysfunction, is a risk factor for erectile dysfunction (ED). Furthermore, the upregulation of inducible nitric oxide synthase (iNOS) is associated with systemic vascular dysfunction in rats with diabetes. The purpose of this study was to investigate the role of iNOS in diabetes mellitus erectile dysfunction (DMED). First, we developed a type 1 DM rat model using streptozotocin and selected those that developed DMED. Then, we injected these rats with the 1400W, an iNOS inhibitor, for 10 weeks and subsequently assessed their ED. Lastly, we performed various molecular studies and histopathological analyses of penile tissues collected from these rats after the experiments. Through the histopathological studies, we also found that the treatment restored the ratios of the smooth muscle to collagen fibres, delayed the development of microvascular injury and alleviated the oxidative stress caused by hyperglycaemia. Based on these results, we confirmed that upregulation of iNOS leads to microvascular dysfunction in patients with ED. Overall, we found that inhibition of iNOS displayed beneficial effects in the treatment of ED, suggesting that its mechanism should be further explored.

Systematic Analysis and Biochemical Characterization of the Caffeoyl Shikimate Esterase Gene Family in Poplar.

Caffeoyl shikimate esterase (CSE) hydrolyzes caffeoyl shikimate into caffeate and shikimate in the phenylpropanoid pathway. In this study, we performed a systematic analysis of the CSE gene family and investigated the possible roles of CSE and CSE-like genes in Populus. We conducted a genome-wide analysis of the CSE gene family, including functional and phylogenetic analyses of CSE and CSE-like genes, using the poplar (Populus trichocarpa) genome. Eighteen CSE and CSE-like genes were identified in the Populus genome, and five phylogenetic groups were identified from phylogenetic analysis. CSEs in Group Ia, which were proposed as bona fide CSEs, have probably been lost in most monocots except Oryza sativa. Primary functional classification showed that PoptrCSE1 and PoptrCSE2 had putative function in lignin biosynthesis. In addition, PoptrCSE2, along with PoptrCSE12, might also respond to stress with a function in cell wall biosynthesis. Enzymatic assay of PoptoCSE1 (Populus tomentosa), -2 and -12 showed that PoptoCSE1 and -2 maintained CSE activity. PoptoCSE1 and 2 had similar biochemical properties, tissue expression patterns and subcellular localization. Most of the PoptrCSE-like genes are homologs of AtMAGL (monoacylglycerol lipase) genes in Arabidopsis and may function as MAG lipase in poplar. Our study provides a systematic understanding of this novel gene family and suggests the function of CSE in monolignol biosynthesis in Populus.

The decline in sexual function, psychological disorders (anxiety and depression) and life satisfaction in older men: A cross-sectional study in a hospital-based population.

This study explored the relationships between the decline in sexual function and psychological burdens and life satisfaction in older men with the aim of providing prospective targets for interventions. From January 2016 to January 2019, we selected 1,326 men aged over 50 years old. We adopted the International Index of Erectile Function-5 (IIEF-5), self-estimated intravaginal ejaculatory latency time (IELT), the premature ejaculation diagnostic tool (PEDT), the General Anxiety Disorder-7 (GAD-7), the Patients Health Questionnaire-9 (PHQ-9), the satisfaction with life scale and the control, autonomy, self-realisation and pleasure scale (CASP-19) to measure premature ejaculation, erectile dysfunction and well-being (including, depression, anxiety, and life quality and satisfaction) respectively. The individuals were divided into two main groups: the decline group and the no-decline group. The incidences of erectile dysfunction (ED), premature ejaculation (PE), anxiety and depression in men who reported a decline in sexuality were 73.83% (330/447), 63.98% (286/447), 75.84% (339/447) and 68.46% (306/447) respectively. Men who showed a decline in sexuality had significantly worse psychological and life satisfaction/quality scores than those in the no-decline group (p < .001 for all). When they had PE or ED simultaneously, these differences widened. Significantly worsened psychological status and life quality/satisfaction scores could be observed in patients who had declined sexual desire and declined frequency of sex (p < .001 for both). Under the impact of the decline in sexual function, the younger participants (age < 60) had significantly worsened negative emotions and life quality and satisfaction. Based on the results of the study, we found that the decline in sexuality was associated with depression and anxiety and worse life satisfaction and quality. Clinicians need to pay more attention to psychological status and life satisfaction and quality for those patients affected by a decline in sexuality.

Prognostic value of performance status in metastatic renal cell carcinoma patients receiving tyrosine kinase inhibitors: a systematic review and meta-analysis.

BACKGROUND: The association between performance status (PS) and the prognosis of metastatic renal cell carcinoma (mRCC) patients receiving tyrosine kinase inhibitors (TKIs) remains controversial. The aim of this study is to evaluate the prognostic value of PS in mRCC patients treated with TKIs. METHODS: Electronic databases were searched to identify the studies that had assessed the association between pretreatment PS and prognosis in mRCC patients receiving TKIs. Hazard ratios (HRs) and 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) from eligible studies were used to calculate combined HRs. The heterogeneity across the included studies was assessed by Cochrane's Q test and I2 statistic. The Begg's funnel plot and Egger's linear regression teats were used to evaluate the potential publication bias. The meta-analysis was performed with RevMan 5.3 and Stata SE12.0 according to the PRISMA guidelines. RESULTS: A total of 6780 patients from 19 studies were included in this meta-analysis. The results showed that a poor PS was an effective prognostic factor of both OS (pooled HR: 2.08, 95% CI: 1.78-2.45) and PFS (pooled HR: 1.51, 95% CI: 1.20-1.91). Subgroup analysis revealed that poor PS significantly associated with poor OS and PFS in studies using Karnofsky PS scale (OS, pooled HR: 2.20, 95% CI: 1.65-2.94; PFS, pooled HR: 1.74, 95% CI: 1.19-2.56), conducted in Asia (OS, pooled HR: 2.25, 95% CI: 1.71-2.95; PFS, pooled HR: 1.73, 95% CI: 1.14-2.64) and Newcastle-Ottawa Scale score of 8 (OS, pooled HR: 2.61, 95% CI: 1.92-3.55; PFS, pooled HR: 2.43, 95% CI: 1.36-4.33). CONCLUSIONS: This study suggests that a poor PS is significantly associated with poor prognosis in mRCC patients receiving TKIs.

Characteristics of Gut Microbiota in Patients with Erectile Dysfunction: A Chinese Pilot Study.

PURPOSE: Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males. MATERIALS AND METHODS: A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota. RESULTS: We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R²=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas Coprococcus_1, Lachnospiraceae_FCS020_group, Lactococcus, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were depleted in ED patients. Actinomyces showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. Coprococcus_1, Lachnospiraceae_FCS020_group, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were significantly correlated with the IIEF-5 score. Ruminiclostridium_5 and Ruminococcaceae_UCG_002 were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72. CONCLUSIONS: This pilot study identified evident alterations in the gut microbiome composition of ED patients and found Actinomyces was negatively correlated with erectile function, which may be a key pathogenic bacteria.

FSformer: A combined frequency separation network and transformer for LDCT denoising.

Low-dose computed tomography (LDCT) has been widely concerned in the field of medical imaging because of its low radiation hazard to humans. However, under low-dose radiation scenarios, a large amount of noise/artifacts are present in the reconstructed image, which reduces the clarity of the image and is not conducive to diagnosis. To improve the LDCT image quality, we proposed a combined frequency separation network and Transformer (FSformer) for LDCT denoising. Firstly, FSformer decomposes the LDCT images into low-frequency images and multi-layer high-frequency images by frequency separation blocks. Then, the low-frequency components are fused with the high-frequency components of different layers to remove the noise in the high-frequency components with the help of the potential texture of low-frequency parts. Next, the estimated noise images can be obtained by using Transformer stage in the frequency aggregation denoising block. Finally, they are fed into the reconstruction prediction block to obtain improved quality images. In addition, a compound loss function with frequency loss and Charbonnier loss is used to guide the training of the network. The performance of FSformer has been validated and evaluated on AAPM Mayo dataset, real Piglet dataset and clinical dataset. Compared with previous representative models in different architectures, FSformer achieves the optimal metrics with PSNR of 33.7714 dB and SSIM of 0.9254 on Mayo dataset, the testing time is 1.825 s. The experimental results show that FSformer is a state-of-the-art (SOTA) model with noise/artifact suppression and texture/organization preservation. Moreover, the model has certain robustness and can effectively improve LDCT image quality.

Exploring the role of the LkABCG36 transporter in lignin accumulation.

Lignin is a complex biopolymer formed through the condensation of three monomeric precursors known as monolignols. However, the mechanism underlying lignin precursor transport remains elusive, with uncertainty over whether it occurs through passive diffusion or an active energized process. ATP-binding cassette 36 (ABCG36) plays important roles in abiotic stress resistance. In this study, we investigated the transport functions of LkABCG36 (Larix kaempferi) for lignin precursors and the potential effects of LkABCG36 overexpression in plants. LkABCG36 enhanced the ability of tobacco (Nicotiana tabacum) bright yellow-2 (BY-2) cells to resist monolignol alcohol stress. Furthermore, LkABCG36 overexpression promoted lignin deposition in tobacco plant stem tissue. To understand the underlying mechanism, we measured the BY-2 cell ability to export lignin monomers and the uptake of monolignol precursors in inside-out (inverted) plasma membrane vesicles. We found that the transport of coniferyl and sinapyl alcohols is an ATP-dependent process. Our data suggest that LkABCG36 contributes to lignin accumulation in tobacco stem tissues through a mechanism involving the active transport of lignin precursors to the cell wall. These findings shed light on the lignin biosynthesis process, with important implications for enhancing lignin deposition in plants, potentially leading to improved stress tolerance and biomass production.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

The Role of Gut Microbiota in Male Erectile Dysfunction of Rats.

PURPOSE: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. RESULTS: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. CONCLUSIONS: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.