Complete chloroplast genome of endangered species Dipterocarpus retusus Blume (Dipterocarpaceae) and its phylogenetic implications.

Dipterocarpus retusus Blume is an endangered species on the IUCN Red List. In this study, we reported the complete chloroplast (cp) genome of D. retusus (GenBank accession number: OP271853). The cp genome was 154,303 bp long, with a large single-copy (LSC) region of 85,586 bp and a small single-copy (SSC) region of 20,273 bp separated by a pair of inverted repeats (IRs) of 24,222 bp. It encodes 128 genes, including 84 protein-coding genes, 36 tRNA genes, and eight ribosomal RNA genes. We also reconstructed the cp genome phylogeny of Dipterocarpus, which indicated D. retusus was closely related with the sympatric species D. gracilis. This study may contribute valuable information to the phylogenetic relationships within the genus Dipterocarpus.

Research status of polycystic ovary syndrome treatment: a mini review and a bibliometric analysis from 2010 to 2023.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women, often linked to abdominal obesity, insulin resistance, and metabolic issues. With its heterogeneous nature, PCOS treatment should be tailored to individual symptoms and patient preferences. This study examines collaboration networks among countries, institutions, authors, references, and journals related to PCOS treatment. METHODS: Web of Science data was analyzed using VOSviewer and CiteSpace for bibliometric visualization. Chinese and Western medicine treatments for PCOS were reviewed, emphasizing symptom-targeted solutions. RESULTS: Data from 4682 records authored by 400 individuals from 515 institutes in 62 countries revealed China as the leading contributor. Notable authors include Monash University and Richard S. Legro. Common research themes include adipocytes, inflammation, insulin sensitivity, oxidative stress, and the gut microbiome. Tailoring treatment to individual needs is essential, focusing on hyperandrogenism, ovulation, and insulin resistance, with lifestyle counseling to address obesity. CONCLUSION: This bibliometric analysis provides valuable insights into the research status of PCOS treatment. China has made significant contributions, and complementary and alternative therapies, such as traditional Chinese medicine and acupuncture, have also shown beneficial effects recently. The research on inflammation, oxidative stress, and the gut microbiome may provide new targets and strategies for the treatment of PCOS. The recognition of the metabolic problems in PCOS patients facilitates the formulation of more personalized treatment plans to improve the prognosis of patients.

Phytochemical and Flavor Characteristics of Mulberry Juice Fermented with Lactiplantibacillus plantarum BXM2.

Fermentation of mulberry juice not only improves its shelf life, but also effectively enhances their flavor and nutritional quality. This study elucidated the phytochemical and flavor characteristics of mulberry juice fermented with Lactiplantibacillus plantarum BXM2, originally isolated from naturally fermented fruit beverage, through widely targeted metabolomics. The fermentation produced the unique flavor of fermented juice and decreased the pH from 4.15 to 3.19. The metabolomic analysis detected 907 non-volatile metabolites, from which 359 significantly different non-volatile metabolites (up 238, down 121) were screened out. Among 731 identified volatile metabolites, 26 flavor substances were the major contributors to the flavor differences between fermented and unfermented mulberry juices. It is hypothesized that lipid metabolism and amino acid catabolism are crucial pathways for the flavor enhancement of mulberry juice fermented with L. plantarum BXM2. Meanwhile, significant increases of the contents of a variety of bioactive substances, such as indole-3-lactic acid, octadeca-9,12,15-trienoic acid, di-/tri-peptides, etc., conferred additional health potential to BXM2-fermented mulberry juice.

Zona Incerta GABAergic Neurons Facilitate Emergence from Isoflurane Anesthesia in Mice.

The zona incerta (ZI) predominantly consists of gamma-aminobutyric acid (GABAergic) neurons, located adjacent to the lateral hypothalamus. GABA, acting on GABAA receptors, serves as a crucial neuromodulator in the initiation and maintenance of general anesthesia. In this study, we aimed to investigate the involvement of ZI GABAergic neurons in the general anesthesia process. Utilizing in-vivo calcium signal optical fiber recording, we observed a decrease in the activity of ZI GABAergic neurons during isoflurane anesthesia, followed by a significant increase during the recovery phase. Subsequently, we selectively ablated ZI GABAergic neurons to explore their role in general anesthesia, revealing no impact on the induction of isoflurane anesthesia but a prolonged recovery time, accompanied by a reduction in delta-band power in mice under isoflurane anesthesia. Finally, through optogenetic activation/inhibition of ZI GABAergic neurons during isoflurane anesthesia, we discovered that activation of these neurons facilitated emergence without affecting the induction process, while inhibition delayed emergence, leading to fluctuations in delta band activity. In summary, these findings highlight the involvement of ZI GABAergic neurons in modulating the emergence of isoflurane anesthesia.

Helicobacter pylori eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

Objectives: A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia. Methods: PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups. Results: Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found. Conclusion: The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

Altered brain activity associated with premature ejaculation improved by electroacupuncture in rats.

Background: Premature ejaculation (PE) is linked with abnormal brain activity that is modifiable by electroacupuncture (EA). Aim: In this study we aimed to explore the central pathological mechanism underlying EA in treating PE. Methods: Six-week-old male Sprague-Dawley rats were divided into a PE group (n = 8) and a control group (n = 8) according to ejaculatory frequency during copulatory behavior. All rats underwent EA at the Zusanli acupoint (ST-36) for 4 weeks. Magnetic resonance imaging data were collected before and after EA. Outcomes: The behavioral parameters, plasma norepinephrine levels, fractional amplitude of low frequency fluctuation (fALFF), and regional homogeneity (ReHo) were evaluated. Results: The PE group ejaculated more times with shorter latency compared with controls. After EA, the ejaculation frequency of the PE group decreased, and the ejaculation latency period increased, with no changes observed in the control group. Norepinephrine levels were higher in the PE group than in the controls and were positively correlated with ejaculation frequency and negatively correlated with ejaculation latency. The PE group showed lower fALFF in the right striatum and higher ReHo in the brainstem compared with controls. After EA, controls showed decreased fALFF in the right striatum, left olfactory bulb, and dorsal fornix and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, prelimbic system, right basal forebrain region, septal region, and olfactory bulb, while the model group exhibited increased fALFF in the right hypothalamic region, decreased fALFF in the left globus pallidum and right basal forebrain region and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, olfactory bulb, basal forebrain region, dentate gyrus, right dysgranular insular cortex, and striatum. Compared with the controls after EA, the model group showed increased ReHo of the right hypothalamic region and decreased ReHo of the right dysgranular insular cortex. Clinical Implications: These findings might enhance the understanding of PE and contribute to new, targeted therapies for PE. Strengths and Limitations: The therapeutic effects might be achieved by EA inhibiting the activity in brain regions involved in ejaculatory behavior. However, the curative effect of acupuncture might be underestimated due to some curative effects of sham acupuncture used in the control group. Conclusion: In conclusion, the ejaculatory frequency of rats may be reduced and ejaculation latency could be extended by EA at ST-36, which might be achieved by the effects of this treatment on brain activity.

"A diamond-shaped" penoplasty technique with or without concurrent suprapubic liposuction for adult-acquired buried penis: clinical outcomes and patient satisfaction rates.

Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

Sex and Age Influence the Relationship Between Serum Creatinine/Cystatin C and Carotid Plaque in Patients With Type 2 Diabetes Mellitus.

We investigated the effect of sex and age on the association between serum creatinine/cystatin C (CCR) ratio and carotid plaque in patients with type 2 diabetes mellitus (T2DM). The carotid plaque group and the non-plaque group were divided according to cervical vascular ultrasound; the general and biochemical data of the two groups were compared according to CCR, gender, and age. Binary logistic regression was used to analyze the factors influencing carotid plaque. A total of 1429 patients with T2DM were included in this study. On multivariate analysis, CCR was an independent predictor of carotid plaque with an adjusted odds ratio (OR) of 1.681 [1.250-2.260]. The risk of carotid plaque in men with T2DM increased significantly (P < .05) with decreasing levels of CCR. In addition, an association between CCR and carotid plaque was found in individuals with T2DM <65 years of age (P < .05). CCR is strongly associated with the risk of carotid plaques in persons with T2DM and are an independent risk factor for carotid plaques in men and people aged <65 years with T2DM.

Tractography with T1-weighted MRI and associated anatomical constraints on clinical quality diffusion MRI.

Diffusion MRI (dMRI) streamline tractography, the gold-standard for in vivo estimation of white matter (WM) pathways in the brain, has long been considered as a product of WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn to propagate streamlines directly from T1 and anatomical context. Training for this network has previously relied on high resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical scans. We define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. We show that under this metric T1 tractography generated by CoRNN reproduces diffusion tractography with approximately three millimeters of error.

Bunyavirus SFTSV nucleoprotein exploits TUFM-mediated mitophagy to impair antiviral innate immunity.

Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response.Abbreviation: 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.

Major specialized natural products from the endangered plant Heptacodium miconioides, potential medicinal uses and insights into its longstanding unresolved systematic classification.

A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.

Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.

BACKGROUND: Gastric cancer (GC) stands out as one of the most prevalent malignancies affecting the digestive system, characterized by a substantial incidence rate and mortality. Maternal embryonic leucine zipper kinase (MELK) has been implicated in the advancement of various cancer types and the modulation of the tumor microenvironment. This study aims to delve into the involvement of MELK in chemoresistance and the tumor microenvironment of GC. METHODS: The MELK expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry. Lentiviral transfection was employed to establish stable cell lines with either overexpressed or silenced MELK. The impact of MELK on the chemoresistance of GC cells and the polarization of macrophages was investigated through in vitro and in vivo functional assays. Additionally, the correlation between MELK and the cytokines colony-stimulating factor 1 (CSF-1), as well as stromal macrophages, was analysed. The prognostic significance of MELK, CSF-1, and CD206 expression levels in clinical samples was further investigated. RESULTS: MELK was found to be highly expressed in chemoresistant GC cells and tissues. Furthermore, both in vitro and in vivo assays indicated that MELK overexpression conferred chemoresistance in GC cells. Additionally, MELK overexpression was observed to induce M2 macrophage polarization via the CSF-1/JAK2/STAT3 pathway, thereby contributing to chemoresistance within the tumor microenvironment. The expression of MELK in GC tissues from neoadjuvant chemotherapy patients correlated positively with CSF-1 and CD206. Moreover, patients with higher expression levels of MELK, CSF-1, or CD206 exhibited significantly shorter OS and DFS rates. CONCLUSIONS: Our investigation underscores the critical role of MELK in promoting chemoresistance and inducing M2 macrophage polarization in GC. It proposes novel targets and methods for the treatment of GC, as well as prognostic factors for neoadjuvant chemotherapy.

Myelin modulates the process of isoflurane anesthesia through the regulation of neural activity.

AIMS: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia. METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed. RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity. CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.

The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.

PURPOSE: This study investigated the effect of an isocitrate dehydrogenase 1 (IDH1) mutation (mutIDH1) on the invasion and angiogenesis of human glioma cells. METHODS: Doxycycline was used to induce the expression of mutIDH1 in glioma cells. Transwell and wound healing assays were conducted to assess glioma cell migration and invasion. Western blotting and cell immunofluorescence were used to measure the expression levels of various proteins. The influence of bone morphogenetic protein 2 (BMP2) on invasion, angiogenesis-related factors, BMP2-related receptor expression, and changes in Smad signaling pathway-related proteins were evaluated after treatment with BMP2. Differential gene expression and reference transcription analysis were performed. RESULTS: Successful infection with recombinant lentivirus expressing mutIDH1 was demonstrated. The IDH1 mutation promoted glioma cell migration and invasion while positively regulating the expression of vascularization-related factors and BMP2-related receptors. BMP2 exhibited a positive regulatory effect on the migration, invasion, and angiogenesis of mutIDH1-glioma cells, possibly mediated by BMP2-induced alterations in Smad signaling pathway-related factors.After BMP2 treatment, the differential genes of MutIDH1-glioma cells are closely related to the regulation of cell migration and cell adhesion, especially the regulation of Smad-related proteins. KEGG analysis confirmed that it was related to BMP signaling pathway and TGF-ß signaling pathway and cell adhesion. Enrichment analysis of gene ontology and genome encyclopedia further confirmed the correlation of these pathways. CONCLUSION: Mutation of isocitrate dehydrogenase 1 promotes the migration, invasion, and angiogenesis of glioma cells, through its effects on the BMP2-driven Smad signaling pathway. In addition, BMP2 altered the transcriptional patterns of mutIDH1 glioma cells, enriching different gene loci in pathways associated with invasion, migration, and angiogenesis.

Parabrachial nucleus Vglut2 expressing neurons projection to the extended amygdala involved in the regulation of wakefulness during sevoflurane anesthesia in mice.

AIMS: The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2-EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2-EA in alterations of consciousness during sevoflurane anesthesia. METHODS: We first validated vglut2-expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c-Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2-EA activity. Lastly, we modulated PBNvglut2-EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation. RESULTS: The expression of vglut2 in PBN neurons projected to the EA, and c-Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2-EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2-EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased ß and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2-EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2-EA accelerated anesthesia induction. Surprisingly, we found a sex-specific regulation of PBNvglut2-EA in this study. The activity of PBNvglut2-EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2-EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females. CONCLUSIONS: PBNvglut2-EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2-EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia.

Glutamatergic neurons of piriform cortex delay induction of inhalational general anesthesia.

Since their clinical application in the 1840s, the greatest mystery surrounding general anesthesia (GA) is how different kinds of general anesthetics cause reversible unconsciousness, and the precise neural mechanisms underlying the processes. Over past years, although many studies revealed the roles of cortex, thalamus, brainstem, especially the sleep-wake circuits in GA-induced loss of consciousness (LOC),the full picture of the neural circuit mechanism of GA is still largely unknown. Recent studies have focused on the importance of other brain regions. Here, we report that the activity of glutamatergic (Glu) neurons in the piriform cortex (PC), a critical brain region for odor encoding, began to increase during the LOC of GA and gradually recovered after recovery of consciousness. Chemical lesions of the anterior PC (APC) neurons accelerated the induction time of isoflurane anesthesia. Chemogenetic and optogenetic activation of APCGlu neurons prolonged isoflurane and sevoflurane anesthesia induction, whereas APCGlu neuron inhibition displayed the opposite effects. Moreover, the modification of APCGlu neurons did not affect the induction or emergence time of propofol GA. In addition, odor processing may be partially involved in the induction of isoflurane and sevoflurane GA regulated by APCGlu neurons. In conclusion, our findings reveal a critical role of APCGlu neurons in inhalational GA induction.

[Sexual therapy combined with physical methods for the treatment of primary intravaginal anejaculation].

OBJECTIVE: To explore the clinical effect of sexual therapy combined with physical methods in the treatment of primary intravaginal anejaculation (PIAE) and its possible action mechanism. METHODS: Ninety PIAE patients with anxiety symptoms were equally randomized into three groups and treated by sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group A), sexual therapy (group B) or (vacuum negative pressure hydro pneumatic / pneumatic bubble massage (group C). After 15 cycles of treatment, the therapeutic effects were compared among the three groups of patients. RESULTS: The effectiveness rates in groups A, B and C were 86.67%, 46.67% and 30.00%, respectively, with statistically significant differences in the total effectiveness rate, the effective rate of the treatment of anxiety symptoms of the patients and their partners, and the effectiveness rate of the treatment of idiosyncratic masturbation (P<0.05). Pairwise comparison showed that the total effectiveness rate was dramatically higher in group A than in groups B and C (P<0.01), with no statistically significant difference between the latter two groups (P>0.05), that the effectiveness rate of the treatment of anxiety symptoms of the patients and sexual partners was remarkably higher in groups A and B than in C (P<0.01), with no statistically significant difference between the former two groups (P>0.05), and that the effectiveness rate of the treatment of idiosyncratic masturbation was significantly higher in group A than in B and C (P< 0.01), with no statistically significant difference between the latter two (P>0.05). CONCLUSION: PIAE is often accompanied by negative psychological state of the patients and their partners and idiosyncratic masturbation, which responds well to sexual therapy combined with vacuum negative pressure hydro pneumatic / pneumatic bubble massage.

Injectable agents for the induction of Peyronie's disease in model rats: a comparative study.

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-ß1 (TGF-ß1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-ß1, and polidocanol (POL) combined with TGF-ß1. The results showed that injection of TGF-ß1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-ß1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-ß1 combination produced pathological changes and curvature comparable to STS + TGF-ß1 and led to fewer complications. In conclusion, fibrin, STS + TGF-ß1, and POL + TGF-ß1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-ß1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.

Inhibition of Caspase-1-dependent pyroptosis alleviates myocardial ischemia/reperfusion injury during cardiopulmonary bypass (CPB) in type 2 diabetic rats.

Cardiovascular complications pose a significant burden in type 2 diabetes mellitus (T2DM), driven by the intricate interplay of chronic hyperglycemia, insulin resistance, and lipid metabolism disturbances. Myocardial ischemia/reperfusion (MI/R) injury during cardiopulmonary bypass (CPB) exacerbates cardiac vulnerability. This study aims to probe the role of Caspase-1-dependent pyroptosis in global ischemia/reperfusion injury among T2DM rats undergoing CPB, elucidating the mechanisms underlying heightened myocardial injury in T2DM. This study established a rat model of T2DM and compared Mean arterial pressure (MAP), heart rate (HR), and hematocrit (Hct) between T2DM and normal rats. Myocardial cell morphology, infarction area, mitochondrial ROS and caspase-1 levels, NLRP3, pro-caspase-1, caspase-1 p10, GSDMD expressions, plasma CK-MB, cTnI, IL-1ß, and IL-18 levels were assessed after reperfusion in both T2DM and normal rats. The role of Caspase-1-dependent pyroptosis in myocardial ischemia/reperfusion injury during CPB in T2DM rats was examined using the caspase-1 inhibitor VX-765 and the ROS scavenger NAC. T2DM rats demonstrated impaired glucose tolerance but stable hemodynamics during CPB, while showing heightened vulnerability to MI/R injury. This was marked by substantial lipid deposition, disrupted myocardial fibers, and intensified cellular apoptosis. The activation of caspase-1-mediated pyroptosis and increased reactive oxygen species (ROS) production further contributed to tissue damage and the ensuing inflammatory response. Notably, myocardial injury was mitigated by inhibiting caspase-1 through VX-765, which also attenuated the inflammatory cascade. Likewise, NAC treatment reduced oxidative stress and partially suppressed ROS-mediated caspase-1 activation, resulting in diminished myocardial injury. This study proved that Caspase-1-dependent pyroptosis significantly contributes to the inflammation and injury stemming from global MI/R in T2DM rats under CPB, which correlate with the surplus ROS generated by oxidative stress during reperfusion.