Inflammatory proteins mediate male erectile dysfunction via plasma metabolites.

Background: There are no clear conclusions as to whether inflammatory proteins and plasma metabolites influence erectile dysfunction (ED). Aim: In this research, we used Mendelian randomization (MR) analysis to discover a causal relationship between inflammatory proteins, plasma metabolites, and ED. Methods: Raw data with ED, inflammatory proteins, and plasma metabolites were obtained from the MRC IEU OpenGWAS and FinnGen database. After a series of screenings, the remaining single nucleotide polymorphisms were selected as instrumental variables or MR analysis to assess the relationship between genetically predicted inflammatory proteins or plasma metabolites and the pathogenesis of ED. Outcomes: The relationship between inflammatory factors and ED was fully analyzed and elaborated. Results: In the inverse variance-weighted method, there exists a significant causal relationship between 4 types of genetically predicted inflammatory proteins and 50 types of plasma metabolites with the incidence of ED. The primary discovery is that 3 inflammatory proteins, fibroblast growth factor 5, interleukin-22 receptor subunit alpha-1, and protein S100-A12, can impact the risk of ED through plasma metabolites. Clinical Implications: ED metabolites and inflammatory proteins are also closely associated with cardiovascular diseases, warranting further exploration. Strengths and Limitations: Our analysis is based on a European population, limiting its generalizability, the genome-wide association study dataset for ED has a relatively small number of cases, and we hope for larger genome-wide association study datasets for future validation. Conclusion: This study has identified that inflammatory proteins can influence ED through plasma metabolites.

Deep Red Light Driven Hydrogen Evolution by Heterojunction Polymer Dots for Diabetic Wound Healing.

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge •OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo-Pdots nanoreactors effectively scavenged •OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.

A New Method for Bearing Fault Diagnosis across Machines Based on Envelope Spectrum and Conditional Metric Learning.

In recent years, most research on bearing fault diagnosis has assumed that the source domain and target domain data come from the same machine. The differences in equipment lead to a decrease in diagnostic accuracy. To address this issue, unsupervised domain adaptation techniques have been introduced. However, most cross-device fault diagnosis models overlook the discriminative information under the marginal distribution, which restricts the performance of the models. In this paper, we propose a bearing fault diagnosis method based on envelope spectrum and conditional metric learning. First, envelope spectral analysis is used to extract frequency domain features. Then, to fully utilize the discriminative information from the label distribution, we construct a deep Siamese convolutional neural network based on conditional metric learning to eliminate the data distribution differences and extract common features from the source and target domain data. Finally, dynamic weighting factors are employed to improve the convergence performance of the model and optimize the training process. Experimental analysis is conducted on 12 cross-device tasks and compared with other relevant methods. The results show that the proposed method achieves the best performance on all three evaluation metrics.

Analysis of risk factors and development of predictive model for malnutrition in patients with traumatic brain injury.

Malnutrition is a highly prevalent complication in patients with traumatic brain injury (TBI), and it is closely related to the prognosis of patients. Accurate identification of patients at high risk of malnutrition is essential. Therefore, we analyzed the risk factors of malnutrition in patients with TBI and developed a model to predict the risk of malnutrition. A retrospective collection of 345 patients with TBI, and they were divided into malnutrition and comparison groups according to the occurrence of malnutrition. Univariate correlation and multifactor logistic regression analyses were performed to determine patients' malnutrition risk factors. We used univariate and logistic regression (forward stepwise method) analyses to identify significant predictors associated with malnutrition in patients with TBI and developed a predictive model for malnutrition prediction. The model's discrimination, calibration, and clinical utility were evaluated using the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). A total of 216 patients (62.6%) developed malnutrition. Multifactorial logistic regression analysis showed that pulmonary infection, urinary tract infection, dysphagia, application of NGT, GCS score ≤ 8, and low ADL score were independent risk factors for malnutrition in patients with TBI (P < 0.05). The area under the curve of the model was 0.947. Calibration plots showed good discrimination of model calibration. DCA showed that the column line plot models were all clinically meaningful when nutritional interventions were performed over a considerable range of threshold probabilities (0-0.98). Malnutrition is widespread in patients with TBI, and the nomogram is a good predictor of whether patients develop malnutrition.

Copper-Catalyzed Sulfur Alkylation of Sulfenamides with N-Sulfonylhydrazones.

Sulfilimines are valuable compounds in both organic synthesis and pharmaceuticals. In this study, we present a copper-catalyzed sulfur alkylation of sulfenamides with N-sulfonylhydrazones. In contrast to prior findings, hydrazones derived from aldehydes act as donor-type carbene precursors, effectively engaging in coupling with sulfenamides via a copper catalyst, demonstrating exclusive S selectivity. The utility of the protocol was highlighted in the rapid access to a wide range of sulfoximine derivatives.

Medicago truncatula ß-glucosidase 17 contributes to drought and salt tolerance through antioxidant flavonoid accumulation.

Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by ß-glucosidase (BGLU) to form their corresponding flavonoid aglycones. In this study, we isolated three abiotic-responsive BGLU genes (MtBGLU17, MtBGLU21 and MtBGLU22) from Medicago truncatula, and found only the recombinant MtBGLU17 protein could catalyse the hydrolysis of flavonoid glycosides. The recombinant MtBGLU17 protein is active towards a variety of flavonoid glucosides, including glucosides of flavones (apigenin and luteolin), flavonols (kaempferol and quercetin), isoflavones (genistein and daidzein) and flavanone (naringenin). In particular, the recombinant MtBGLU17 protein preferentially hydrolyses flavonoid-7-O-glucosides over their corresponding 3-O-glucosides. The content of luteoin-7-O-glucoside was reduced in the MtBGLU17 overexpression plants but increased in the Tnt-1 insertional mutant lines, whereas luteoin content was increased in the MtBGLU17 overexpression plants but reduced in the Tnt-1 insertional mutant lines. Under drought and salt (NaCl) treatment, the MtBGLU17 overexpression lines showed relatively higher DPPH content, and higher CAT and SOD activity than the wild type control. These results indicated that overexpression lines of MtBGLU17 possess higher antioxidant activity and thus confer drought and salt tolerance, implying MtBGLU17 could be potentially used as a candidate gene to improve plant abiotic stress tolerance.

Seasonal drought promotes citrate accumulation in citrus fruit through the CsABF3-activated CsAN1-CsPH8 pathway.

Plenty of rainfall but unevenly seasonal distribution happens regularly in southern China. Seasonal drought from summer to early autumn leads to citrus fruit acidification, but how seasonal drought regulates citrate accumulation remains unknown. Herein, we employed a set of physiological, biochemical, and molecular approaches to reveal that CsABF3 responds to seasonal drought stress and modulates citrate accumulation in citrus fruits by directly regulating CsAN1 and CsPH8. Here, we demonstrated that irreversible acidification of citrus fruits is caused by drought lasting for > 30 d during the fruit enlargement stage. We investigated the transcriptome characteristics of fruits affected by drought and corroborated the pivotal roles of a bHLH transcription factor (CsAN1) and a P3A-ATPase gene (CsPH8) in regulating citrate accumulation in response to drought. Abscisic acid (ABA)-responsive element binding factor 3 (CsABF3) was upregulated by drought in an ABA-dependent manner. CsABF3 activated CsAN1 and CsPH8 expression by directly and specifically binding to the ABA-responsive elements (ABREs) in the promoters and positively regulated citrate accumulation. Taken together, this study sheds new light on the regulatory module ABA-CsABF3-CsAN1-CsPH8 responsible for citrate accumulation under drought stress, which advances our understanding of quality formation of citrus fruit.

Minisci-Type Dehydrogenative Coupling of N-Heteroaromatic Rings with Inert C(sp3)-H Enabled by a Visible-Light-Catalyzed Intermolecular Hydrogen Atom Transfer Process.

The Minisci-type dehydrogenative coupling of N-heteroaromatic rings with inert C-H or Si-H partners via visible-light-catalyzed hydrogen atom transfer has been reported. This methodology allows the coupling reactions to be carried out in water as a solvent under air atmospheric conditions with visible-light illumination. A wide range of inert C-H and Si-H partners could be directly coupled with various N-aromatic heterocycles to deliver products in good to excellent yields.

Fabrication and Characterization of Silicon-Based Antimonene Thin Film via Electron Beam Evaporation.

Antimonene has attracted much attention due to its excellent characteristics of high carrier mobility, thermoelectric properties and high stability. It has great application prospects in Q-switched lasers, laser protection and spintronics. At present, the epitaxy growth of antimonene mainly depends on molecular beam epitaxy. We have successfully prepared antimonene films on silicon, germanium/silicon substrates for the first time using electron beam evaporation coating and studied the effects of the deposition rate and substrate on the preparation of antimonene; film characterization was performed via confocal microprobe Raman spectroscopy, via X-ray diffraction and using a scanning electron microscope. Raman spectroscopy showed that different deposition rates can lead to the formation of different structures of antimonene, such as α phase and ß phase. At the same time, it was found that the growth of antimonene is also affected by different substrates and ion beams.

Injectable, self-healing hyaluronic acid-based hydrogels for spinal cord injury repair.

The cystic cavity that develops following spinal cord injury is a major obstacle for repairing spinal cord injury (SCI). The injectable self-healing biomaterials treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury. Herein, a natural extracellular matrix (ECM) biopolymer hyaluronic acid-based hydrogel was developed based on multiple dynamic covalent bonds. The hydrogels exhibited excellent injectable and self-healing properties, could be effectively injected into the injury site, and filled the lesion cavity to accelerate the tissue repair of traumatic SCI. Moreover, the hydrogels were compatible with cells and various tissues and possessed proper stiffness matched with nervous tissue. Additionally, when implanted into the injured spinal cord site, the hyaluronic acid-based hydrogel promoted axonal regeneration and functional recovery by accelerating remyelination, axon regeneration, and angiogenesis. Overall, the injectable self-healing hyaluronic acid-based hydrogels are ideal biomaterials for treating traumatic SCI.

Self-Oxidated Hydrophilic Chitosan Fibrous Mats for Fatal Hemorrhage Control.

Enriching erythrocytes and platelets in seconds and providing a fast seal in bleeding sites is vital to fatal hemorrhage control. Herein, hydrophilic chitosan fibrous mats (CECS-D mats) are fabricated by introducing hydrophilic carboxyethyl groups and subsequent catechol groups onto chitosan fibers. Due to strong hydrophilicity, CECS-D mats exhibit rapid liquid-absorption capacity, especially instantaneous absorptivity to the rabbit blood, which can achieve erythrocyte and platelet aggregations quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the mats are self-oxidated to form quinone-amine adducts or quinone multimers by adjusting pH conditions, which not only provides tissue adhesion but also induces erythrocyte aggregation and platelet adhesion, further enhancing the seal and triggering quick closure to achieve fast hemostasis. Therefore, the mats reveal superior hemostatic performance in rabbit liver and spleen models over CECS mats and gauze. Especially in the fatal femoral artery injury model of rabbits, the mats reduce the blood loss by ∼75% and shortened the bleeding time by ∼50% compared with CECS mats, which have been reported to have the same hemostatic effect as commercialized Celox products in a swine femoral artery injury model. Besides, the mats are cytocompatible and degradable as well as antibacterial. This chitosan mat is a promising hemostatic material for fatal hemorrhage control.

Pd-Catalyzed Asymmetric Larock Indole Synthesis to Access Axially Chiral N-Arylindoles.

Larock indole synthesis is one of the most straightforward and efficient methods for the synthesis of indoles; however, there has been no asymmetric version yet for the construction of indole-based axially chiral N-arylindoles since its initial report in 1991. Herein we report the first example of an asymmetric Larock indole synthesis by employing a chiral sulfinamide phosphine (SadPhos) ligand (Ming-Phos) with palladium. It allows rapid construction of a wide range of axially chiral N-arylindole compounds in good yields up to 98:2 er. The application of this unique chiral scaffold as an organocatalyst is promising. Furthermore, a kinetic study has revealed that the alkyne migratory insertion is the rate-determining step, which has been proven by the density functional theory (DFT) calculations. Additionally, DFT studies also suggest that the N-C dihedral difference caused by the steric hindrance of the ligand contributes to enantioselectivity control.

Antibacterial hyaluronic acid hydrogels with enhanced self-healing properties via multiple dynamic bond crosslinking.

The self-healing hydrogel offering intrinsic antibacterial activity is often required for the treatment of wounds because it can provide effective wound protection and prevent wound infection. Herein, antibacterial hyaluronic acid hydrogels with enhanced self-healing performances are prepared by multiple dynamic-bond crosslinking between aldehyde hyaluronic acid, 3, 3'- dithiobis (propionyl hydrazide) and fungal-sourced quaternized chitosan. Due to the formation of these different types of reversible interactions e.g. hydrazone bonds, disulfide bonds, and electrostatic interactions, the hyaluronic acid hydrogels can gel rapidly and exhibit excellent self-healing ability, which can heal completely within 1 h. Furthermore, the hydrogels show good antibacterial activity against E. coli and S. aureus with an inhibition ratio of ~100 % and above 75 %, respectively. Additionally, the hydrogels are cytocompatible, which makes them the potential for biomedical applications e.g. cell culture, tissue engineering, and wound dressing.

Autophagy markers, cognitive deficits and depressive symptoms in Parkinson's disease.

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50-80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = - 0.002, t = - 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = - 0.001, t = - 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.

Live Imaging of 3D Hanging Drop Arrays through Manipulation of Light-Responsive Pyroelectric Slippery Surface and Chip Adhesion.

Three-dimensional (3D) hanging drop cell culture is widely used in organoid culture because of its lack of selection pressure and rapid cell aggregation. However, current hanging drop technology has limitations, such as a dependence on complex microfluidic transport channels or specific capillary force templates for drop formation, which leads to unchangeable drop features. These methods also hinder live imaging because of space and complexity constraints. Here, we have developed a hanging drop construction method and created a flexible 3D hanging drop construction platform composed of a manipulation module and an adhesion module. Their harmonious operation allows for the easy construction of hanging drops of varying sizes, types, and patterns. Our platform produces a cell hanging drop chip with small sizes and clear fields of view, thereby making it compatible with live imaging. This platform has great potential for personalized medicine, cancer and drug discovery, tissue engineering, and stem cell research.

Construction of the metabolic reprogramming-associated gene signature for clear cell renal cell carcinoma prognosis prediction.

BACKGROUND: Metabolism reprogramming is a hallmark that associates tumor growth, metastasis, progressive, and poor prognosis. However, the metabolism-related molecular patterns and mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear. Herein, the purpose of this study was to identify metabolism-related molecular pattern and to investigate the characteristics and prognostic values of the metabolism-related clustering. METHODS: We comprehensively analyzed the differentially expressed genes (DEGs), and metabolism-related genes (MAGs) in ccRCC based on the TCGA database. Consensus clustering was used to construct a metabolism-related molecular pattern. Then, the biological function, molecular characteristics, Estimate/immune/stomal scores, immune cell infiltration, response to immunotherapy, and chemotherapy were analyzed. We also identified the DEGs between subclusters and constructed a poor signature and risk model based on LASSO regression cox analysis and univariable and multivariable cox regression analyses. Then, a predictive nomogram was constructed and validated by calibration curves. RESULTS: A total of 1942 DEGs (1004 upregulated and 838 downregulated) between ccRCC tumor and normal samples were identified, and 254 MRGs were screened out from those DEGs. Then, 526 ccRCC patients were divided into two subclusters. The 7 metabolism-related pathways enriched in cluster 2. And cluster 2 with high Estimate/immune/stomal scores and poor survival. While, cluster 1 with higher immune cell infiltrating, expression of the immune checkpoint, IFN, HLA, immune activation-related genes, response to anti-CTLA4 treatment, and chemotherapy. Moreover, we identified 295 DEGs between two metabolism-related subclusters and constructed a 15-gene signature and 9 risk factors. Then, a risk score was calculated and the patients into high- and low-risk groups in TCGA-KIRC and E-MTAB-1980 datasets. And the prediction viability of the risk score was validated by ROC curves. Finally, the clinicopathological characteristics (age and stage), risk score, and molecular clustering, were identified as independent prognostic variables, and were used to construct a nomogram for 1-, 3-, 5-year overall survival predicting. The calibration curves were used to verify the performance of the predicted ability of the nomogram. CONCLUSION: Our finding identified two metabolism-related molecular subclusters for ccRCC, which facilitates the estimation of response to immunotherapy and chemotherapy, and prognosis after treatment.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Weighted gene coexpression correlation network analysis reveals the potential molecular regulatory mechanism of citrate and anthocyanin accumulation between postharvest 'Bingtangcheng' and 'Tarocco' blood orange fruit.

BACKGROUND: Organic acids and anthocyanins are the most important compounds for the flavor and nutritional quality of citrus fruit. However, there are few reports on the involvement of co-regulation of citrate and anthocyanin metabolism. Here, we performed a comparative transcriptome analysis to elucidate the genes and pathways involved in both citrate and anthocyanin accumulation in postharvest citrus fruit with 'Tarocco' blood orange (TBO; high accumulation) and 'Bingtangcheng' sweet orange (BTSO; low accumulation). RESULTS: A robust core set of 825 DEGs were found to be temporally associated with citrate and anthocyanin accumulation throughout the storage period through transcriptome analysis. Further according to the results of weighted gene coexpression correlation network analysis (WGCNA), the turquoise and brown module was highly positively correlated with both of the content of citrate and anthocyanin, and p-type ATPase (PH8), phosphoenolpyruvate carboxylase kinase (PEPCK), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H) and glutathione S transferase (GST) were considered key structural genes. Moreover, MYB family transcription factor (PH4), Zinc finger PHD-type transcription factor (CHR4, HAC12), Zinc finger SWIM-type transcription factor (FAR1) and Zinc finger C3H1-type transcription factor (ATC3H64) were considered hub genes related to these structural genes. Further qRT-PCR analysis verified that these transcription factors were highly expressed in TBO fruit and their expression profiles were significantly positively correlated with the structural genes of citrate and anthocyanin metabolism as well as the content of citrate and anthocyanin content. CONCLUSIONS: The findings suggest that the CHR4, FAR1, ATC3H64 and HAC12 may be the new transcription regulators participate in controlling the level of citrate and anthocyanin in postharvest TBO fruit in addition to PH4. These results may providing new insight into the regulation mechanism of citrate and anthocyanin accumulation in citrus fruit.

Temperature-insensitive and fabrication-tolerant coarse wavelength division (de)multiplexing on a silica platform using an angled multimode interferometer.

Wavelength division (de)multiplexing (WDM) device is a crucial component for optical transmission networks. In this paper, we demonstrate a 4 channel WDM device with a 20 nm wavelength spacing on silica based planar lightwave circuits (PLC) platform. The device is designed using an angled multimode interferometer (AMMI) structure. Since there are fewer bending waveguides than other WDMs, the device footprint is smaller, at 21 mm × 0.4 mm. Owing to the low thermo-optic coefficient (TOC) of silica, a low temperature sensitivity of 10 pm/°C is achieved. The fabricated device exhibits high performance of an insertion loss (IL) lower than 1.6 dB, a polarization dependent loss (PDL) lower than 0.34 dB, and the crosstalk between adjacent channels lower than -19 dB. The 3 dB bandwidth is 12.3∼13.5 nm. Moreover, the device shows a high tolerance with a sensitivity of central wavelength to the width of multimode interferometer < 43.75 pm/nm.