Sustainable lithium extraction enabled by responsive metal-organic frameworks with ion-sieving adsorption effects.

Metal-organic frameworks (MOFs) are superior ion adsorbents for selectively capturing toxic ions from water. Nevertheless, they have rarely been reported to have lithium selectivity over divalent cations due to the well-known flexibility of MOF framework and the similar physiochemical properties of Li+ and Mg2+. Herein, we report an ion-sieving adsorption approach to design sunlight-regenerable lithium adsorbents by subnanoporous MOFs for efficient lithium extraction. By integrating the ion-sieving agent of MOFs with light-responsive adsorption sites of polyspiropyran (PSP), the ion-sieving adsorption behaviors of PSP-MOFs with 6.0, 8.5, and 10.0 Å windows are inversely proportional to their pore size. The synthesized PSP-UiO-66 with a narrowest window size of 6.0 Å shows high LiCl adsorption capacity up to 10.17 mmol g-1 and good Li+/Mg2+ selectivity of 5.8 to 29 in synthetic brines with Mg/Li ratio of 1 to 0.1. It could be quickly regenerated by sunlight irradiation in 6 min with excellent cycling performance of 99% after five cycles. This work sheds light on designing selective adsorbents using responsive subnanoporous materials for environmentally friendly and energy-efficient ion separation and purification.

The transcription factors ZmNAC128 and ZmNAC130 coordinate with Opaque2 to promote endosperm filling in maize.

Endosperm filling in maize (Zea mays), which involves nutrient uptake and biosynthesis of storage reserves, largely determines grain yield and quality. However, much remains unclear about the synchronization of these processes. Here, we comprehensively investigated the functions of duplicate NAM, ATAF1/2, and CUC2 (NAC)-type transcription factors, namely, ZmNAC128 and ZmNAC130, in endosperm filling. The gene-edited double mutant zmnac128 zmnac130 exhibits a poorly filled kernel phenotype such that the kernels have an inner cavity. RNA sequencing and protein abundance analysis revealed that the expression of many genes involved in the biosynthesis of zein and starch is reduced in the filling endosperm of zmnac128 zmnac130. Further, DNA affinity purification and sequencing combined with chromatin-immunoprecipitation quantitative PCR and promoter transactivation assays demonstrated that ZmNAC128 and ZmNAC130 are direct regulators of 3 (16-, 27-, and 50-kD) γ-zein genes and 6 important starch metabolism genes (Brittle2 [Bt2], pullulanase-type starch debranching enzyme [Zpu1], granule-bound starch synthase 1 [GBSS1], starch synthase 1 [SS1], starch synthase IIa [SSIIa], and sucrose synthase 1 [Sus1]). ZmNAC128 and ZmNAC130 recognize an additional cis-element in the Opaque2 (O2) promoter to regulate its expression. The triple mutant zmnac128 zmnac130 o2 exhibits extremely poor endosperm filling, which results in more than 70% of kernel weight loss. ZmNAC128 and ZmNAC130 regulate the expression of the transporter genes sugars that will eventually be exported transporter 4c (ZmSWEET4c), sucrose and glucose carrier 1 (ZmSUGCAR1), and yellow stripe-like2 (ZmYSL2) and in turn facilitate nutrient uptake, while O2 plays a supporting role. In conclusion, ZmNAC128 and ZmNAC130 cooperate with O2 to facilitate endosperm filling, which involves nutrient uptake in the basal endosperm transfer layer (BETL) and the synthesis of zeins and starch in the starchy endosperm (SE).

Retraction Note: Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ficolin-A/2 Aggravates Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D-Induced Pyroptosis.

Neutrophil extracellular traps (NETs) and pyroptosis are critical events in lung injury. This study investigated whether ficolin-A influenced NET formation through pyroptosis to exacerbate lipopolysaccharide (LPS)-induced lung injury. The expression of ficolin-A/2, NETs, and pyroptosis-related molecules was investigated in animal and cell models. Knockout and knockdown (recombinant protein) methods were used to elucidate regulatory mechanisms. The Pearson correlation coefficient was used to analyze the correlation between ficolins and pyroptosis- and NET-related markers in clinical samples. In this study, ficolin-2 (similar to ficolin-A) showed significant overexpression in patients with acute respiratory distress syndrome. In vivo, knockout of Fcna, but not Fcnb, attenuated lung inflammation and inhibited NET formation in the LPS-induced mouse model. DNase I further alleviated lung inflammation and NET formation in Fcna knockout mice. In vitro, neutrophils derived from Fcna-/- mice showed less pyroptosis and necroptosis than those from the control group after LPS stimulation. Additionally, GSDMD knockdown or Nod-like receptor protein 3 inhibitor reduced NET formation. Addition of recombinant ficolin-2 protein to human peripheral blood neutrophils promoted NET formation and pyroptosis after LPS stimulation, whereas Fcn2 knockdown had the opposite effect. Acute respiratory distress syndrome patients showed increased levels of pyroptosis- and NET-related markers, which were correlated positively with ficolin-2 levels. In conclusion, these results suggested that ficolin-A/2 exacerbated NET formation and LPS-induced lung injury via gasdermin D-mediated pyroptosis.

Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation.

Signal transducer and activator of transcription 3 (STAT3) has a critical role in regulating cell fate, inflammation and immunity1,2. Cytokines and growth factors activate STAT3 through kinase-mediated tyrosine phosphorylation and dimerization3,4. It remains unknown whether other factors promote STAT3 activation through different mechanisms. Here we show that STAT3 is post-translationally S-palmitoylated at the SRC homology 2 (SH2) domain, which promotes the dimerization and transcriptional activation of STAT3. Fatty acids can directly activate STAT3 by enhancing its palmitoylation, in synergy with cytokine stimulation. We further identified ZDHHC19 as a palmitoyl acyltransferase that regulates STAT3. Cytokine stimulation increases STAT3 palmitoylation by promoting the association between ZDHHC19 and STAT3, which is mediated by the SH3 domain of GRB2. Silencing ZDHHC19 blocks STAT3 palmitoylation and dimerization, and impairs the cytokine- and fatty-acid-induced activation of STAT3. ZDHHC19 is frequently amplified in multiple human cancers, including in 39% of lung squamous cell carcinomas. High levels of ZDHHC19 correlate with high levels of nuclear STAT3 in patient samples. In addition, knockout of ZDHHC19 in lung squamous cell carcinoma cells significantly blocks STAT3 activity, and inhibits the fatty-acid-induced formation of tumour spheres as well as tumorigenesis induced by high-fat diets in an in vivo mouse model. Our studies reveal that fatty-acid- and ZDHHC19-mediated palmitoylation are signals that regulate STAT3, which provides evidence linking the deregulation of palmitoylation to inflammation and cancer.

Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4.

In patients with sepsis, neutrophil apoptosis tends to be inversely proportional to the severity of sepsis, but its mechanism is not yet clear. This study aimed to explore the mechanism of fatty acid binding protein 4 (FABP4) regulating neutrophil apoptosis through combined analysis of gut microbiota and short-chain fatty acids (SCFAs) metabolism. First, neutrophils from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced acute respiratory distress syndrome (ARDS) were purified and isolated RNA was applied for sequencing. Then, the cecal ligation and puncture (CLP) method was applied to induce the mouse sepsis model. After intervention with differential SCFAs sodium acetate, neutrophil apoptosis and FABP4 expression were further analyzed. Then, FABP4 inhibitor BMS309403 was used to treat neutrophils. We found CLP group had increased lung injury score, lung tissue wet/dry ratio, lung vascular permeability, and inflammatory factors IL-1ß, TNF-α, IL-6, IFN-γ, and CCL3 levels in both bronchoalveolar lavage fluid and lung tissue. Additionally, FABP4 was lower in neutrophils of ARDS patients and mice. Meanwhile, CLP-induced dysbiosis of gut microbiota and changes in SCFAs levels were observed. Further verification showed that acetic acids reduced neutrophil apoptosis and FABP4 expression via FFAR2. Besides, FABP4 affected neutrophil apoptosis through endoplasmic reticulum (ER) stress, and neutrophil depletion alleviated the promotion of ARDS development by BMS309403. Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage.

Mild-Temperature Supercritical Water Confined in Hydrophobic Metal-Organic Frameworks.

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway.

Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway.In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Counterintuitive Trend of Intrusion Pressure with Temperature in the Hydrophobic Cu2(tebpz) MOF.

Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu2(3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi) increases with T. For higher T values, Pi first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2(tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi. Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T.

HPV-associated cervicovaginal microbiome and host metabolome characteristics.

BACKGROUND: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. RESULTS: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. CONCLUSION: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

5.4 W, 2.35†µm cascaded Raman fiber laser pumped by dissipative soliton resonance-like pulses.

We present a nonlinear amplifying loop mirror-based mode-locked fiber laser. By adjusting the pump power, the proposed laser exhibits a dissipative soliton resonance (DSR)-like pulse operation with a maximum pulse width of 150 ns. Subsequently, a three-stage Tm3+-doped fiber amplifier is implemented using a single-mode double-cladding Tm3+-doped fiber to increase the DSR-like pulse output power to 52.5 W, achieving a pump slope efficiency of 47.1% in the main amplifier. A 25 m first-order Raman-gain fiber (UHNA7) is pumped by a DSR-like pulse, and 16.3 W of pure 2.135 µm first-order Raman light with a spectral purity of 73.4% is obtained. Finally, 5.4 W of 2.35 µm second-order Raman light with a spectral purity of 66% is obtained using a 10 m 98% germania-core fiber as a second-order Raman-gain fiber cascaded after UHNA7 fiber. To the best of our knowledge, this is the highest output power ever obtained from a 2.3 µm laser.

Over 3.8 W, 3.4†µm picosecond mid-infrared parametric conversion based on a simplified one-to-many scheme.

In this paper, we demonstrate a simplified one-to-many scheme for efficient mid-infrared (MIR) parametric conversion. Such a scheme is based on a continuous wave (CW) single longitudinal mode master oscillator power-amplifier (MOPA) fiber system as the signal source and a picosecond pulsed MOPA fiber system, exhibiting multiple longitudinal modes, as the pump source. The signal and pump beams are combined and co-coupled into a piece of 50-mm long 5% MgO-doped PPLN crystal for the parametric conversion. As high as ∼3.82 W average power at a central idler wavelength of ∼3.4 µm is achieved when the launched pump and signal powers are ∼41.73 and ∼11.45 W, respectively. Above some threshold value, the delivered idler power shows a roll-over effect against the signal power and saturation-like effect against the pump power. Consequently, the highest conversion efficiency is observed at such a threshold pump power. To the best of our knowledge, our result represents the highest average power produced from any single-pass parametric conversion source with >3 µm idler wavelength feeding with a CW signal. Moreover, our proposed scheme can simplify the design of parametric conversion system significantly and meanwhile make the system more robust in applications. This is attributed to two main aspects. Firstly, the scheme's one-to-many feature can reduce wavelength sensitivity remarkably in the realization of quasi-phase-matching. Secondly, for moderate power requirement it does not always require a high peak power synchronized pulsed signal source; a CW one can be an alternative, thereby making the system free from complex time synchronization and the related time jitter.

Phosphoregulation in the N-terminus of NRT2.1 affects nitrate uptake by controlling the interaction of NRT2.1 with NAR2.1 and kinase HPCAL1 in Arabidopsis.

NRT2.1, the major high affinity nitrate transporter in roots, can be phosphorylated at five different sites within the N- and the C-terminus. Here, we characterized the functional relationship of two N-terminal phosphorylation sites, S21 and S28, in Arabidopsis. Based on a site-specific correlation network, we identified a receptor kinase (HPCAL1, AT5G49770), phosphorylating NRT2.1 at S21 and resulting in active nitrate uptake. HPCAL1 itself was regulated by phosphorylation at S839 and S870 within its kinase domain. In the active state, when S839 was dephosphorylated and S870 was phosphorylated, HPCAL1 was found to interact with the N-terminus of NRT2.1, mainly when S28 was dephosphorylated. Phosphorylation of NRT2.1 at S21 resulted in a reduced interaction of NRT2.1 with its activator NAR2.1, but nitrate transport activity remained. By contrast, phosphorylated NRT2.1 at S28 enhanced the interaction with NAR2.1, but reduced the interaction with HPCAL1. Here we identified HPCAL1 as the kinase affecting this phospho-switch through phosphorylation of NRT2.1 at S21.

GLO1 regulates hepatocellular carcinoma proliferation and migration through the cell cycle pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. METHODS: Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1's impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. RESULTS: Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. CONCLUSIONS: GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.

Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation.

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m1A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), pseudouridine (Ψ) and N7-methylguanosine (m7G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m6A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.

Variations in objectively measured sleep parameters in patients with different premature ejaculation syndromes.

BACKGROUND: Poor sleep quality is now a cause of sexual dysfunction. AIM: To investigate variations in sleep quality among patients with different types of premature ejaculation (PE) and a control group. METHODS: Patients with PE were categorized into groups according to 4 types: lifelong (LPE), acquired (APE), variable (VPE), and subjective (SPE). Basic demographic information about the participants was first collected, and then clinical data were obtained. OUTCOMES: Outcomes included the 5-item International Index of Erectile Function, Premature Ejaculation Diagnostic Tool, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pittsburgh Sleep Quality Index, self-estimated intravaginal ejaculation latency time (minutes), and sleep monitoring parameters obtained from a wearable device (Fitbit Charge 2). RESULTS: A total of 215 participants were enrolled in the study, of which 136 patients with PE were distributed as follows: LPE (31.62%), APE (42.65%), VPE (10.29%), and SPE (15.44%). Subjective scales showed that patients with APE were accompanied by a higher prevalence of erectile dysfunction, anxiety, and depression, as well as poorer sleep quality (assessed by the Pittsburgh Sleep Quality Index). The results of objective sleep parameters revealed that average durations of sleep onset latency (minutes) and wake after sleep onset (minutes) in patients with APE (mean ± SD; 20.03 ± 9.14, 55 ± 23.15) were significantly higher than those with LPE (15.07 ± 5.19, 45.09 ± 20.14), VPE (13.64 ± 3.73, 38.14 ± 11.53), and SPE (14.81 ± 4.33, 42.86 ± 13.14) and the control group (12.48 ± 3.45, 37.14 ± 15.01; P < .05). The average duration of rapid eye movement (REM; minutes) in patients with APE (71.34 ± 23.18) was significantly lower than that in patients with LPE (79.67 ± 21.53), VPE (85.93 ± 6.93), and SPE (80.86 ± 13.04) and the control group (86.56 ± 11.93; P < .05). Similarly, when compared with the control group, patients with LPE had significantly longer durations of sleep onset latency and wake after sleep onset and a significantly shorter duration of REM sleep. CLINICAL IMPLICATIONS: Our study suggests that clinicians should pay attention not only to male physical assessment but also to mental health and sleep quality. STRENGTHS AND LIMITATIONS: This study suggests that changes in sleep structure occur in patients with PE, which may provide some direction for future research. However, the cross-sectional study design does not allow us to conclude that sleep is a risk factor for PE. CONCLUSION: After controlling for traditional parameters such as age, erectile dysfunction, anxiety, and depression, sleep parameters are independently associated with PE. Patients with APE and LPE show significant alterations in sleep parameters, with patients with APE having notably poorer sleep quality, whereas patients with VPE and SPE have sleep parameters similar to controls.

Chronic sleep deprivation induces erectile dysfunction through increased oxidative stress, apoptosis, endothelial dysfunction, and corporal fibrosis in a rat model.

BACKGROUND: Sleep is foundational for nocturnal erections, facilitating nutrient exchange and waste removal, which has brought widespread attention to the relationship between sleep and erectile dysfunction (ED). However, there is currently a lack of basic research confirming whether chronic sleep deprivation (CSD) leads to erectile impairment and its underlying pathological mechanisms. AIM: The study sought to investigate whether CSD impairs erectile function in rats and the potential tissue damage it may cause in rats. METHODS: The modified multiple platform method was employed to induce CSD in 14 rats, randomly divided into a platform control group and a CSD group. After 3 weeks, erectile function was evaluated by measuring intracavernosal pressure following cavernous nerve stimulation. OUTCOMES: Arterial blood samples were then analyzed for testosterone levels, and cavernous tissues were processed for advanced molecular biology assays, including Western blotting and immunofluorescence. RESULTS: After inducing CSD, rats exhibited a marked reduction in erectile function, yet their serum testosterone levels remained statistically unchanged when compared with the control group. More importantly, rats in the CSD group exhibited a significant increase in oxidative stress levels, accompanied by low expression of HO-1 and high expression of NOX1 and NOX4. Subsequently, elevated oxidative stress induced increased apoptosis in smooth muscle and endothelial cells, as evidenced by significant decreases in CD31 and α-smooth muscle actin expression in the CSD group, demonstrated through Western blotting and immunofluorescence assays. Endothelial cell apoptosis led to a significant decrease in endothelial nitric oxide synthase, resulting in lowered levels of nitric oxide and cyclic guanosine monophosphate, which severely impaired the erectile mechanism. Additionally, activation of the transforming growth factor ß1 fibrotic pathway led to increased levels of tissue fibrosis, resulting in irreversible damage to the penile tissue in the CSD group. CLINICAL IMPLICATIONS: Our study lacks further exploration of the molecular mechanisms linking CSD and ED, representing a future research focus for potential targeted therapies. STRENGTHS AND LIMITATIONS: Our findings demonstrated that CSD significantly impairs erectile function in rats. CONCLUSION: CSD severely impairs erectile function in rats. When exposed to CSD, rats exhibit significantly elevated oxidative stress levels, which lead to increased tissue apoptosis, endothelial dysfunction, and ultimately irreversible fibrotic changes in the tissues. Further researches into the potential molecular mechanisms are needed to identify possible therapeutic targets for ED related to CSD.

A novel strategy to induce penile erection during penile doppler ultrasound: oral sildenafil administration plus alprostadil injection.

OBJECTIVES: To evaluate the efficacy of a novel approach to achieve the optimal penile erection during the penile doppler ultrasound (PDU) examination, which was oral sildenafil combined alprostadil injection. MATERIALS AND METHODS: A total of 60 ED patients were enrolled in our prospective study, and they were randomly assigned to two group with different PDU order. The approaches assisted the PDU included two models, mode A meaning injection of 15 µg alprostadil and model B meaning oral sildenafil 100 mg plus injection of 15 µg alprostadil. The PDU parameters were measured continuously before induced erection, and 5, 10, 15, 20, 25 min. RESULTS: Each group included 30 ED patients with similar clinical characteristics. After pooling the results together, the PSV, EDV, and RI were all improved significantly, when adding the oral sildenafil administration to assist PDU. Also, the clinical response of oral sildenafil administration plus alprostadil injection was better than that in alprostadil injection alone (p = 0.016). The arterial ED were decreased from 31.67% to 15.00% with the P value 0.031, and the mixed ED was also decreased statistically (23.33% vs 8.33%, p = 0.024). CONCLUSION: Oral sildenafil administration plus alprostadil injection could improve the diagnostic accuracy of PDU.

Effect and mechanism of needleless transcutaneous neuromodulation on gastrointestinal function after pancreaticoduodenectomy.

BACKGROUND: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. METHODS: A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. RESULTS: 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(ß = - 0.349, p = 0.035). CONCLUSION: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.