Adsorption Mechanisms of CO2 on Macroporous Ion-Exchange Resin Organic Amine Composite Materials by the Density Functional Theory.

The adsorption mechanisms of CO2 on macroporous cation exchange resin (MCER), D001 ion-exchange resin, and macroporous ion-exchange resin organic amine composite materials (MCER-DEA and D001-PEI) were studied by density functional theory (DFT). The adsorption energies and Mulliken atomic charges in the adsorption process were analyzed, indicating that CO2 on MCER and D001 were physisorbed. The adsorption heat of the adsorption process of MCER-DEA and D001-PEI was calculated by the Monte Carlo method, and it was found that the adsorption process of CO2 by MCER-DEA and D001-PEI was both physical adsorption and chemical adsorption. Besides, the chemical adsorption mechanism of CO2 by MCER-DEA and D001-PEI was investigated by analyzing the free energy barrier and the Gibbs free energy change of the involved chemical reactions and the results showed that the free energy barrier required for MCER-DEA to generate zwitterion was 26.23 kcal/mol, which is 1.74 times that of D001-PEI (15.04 kcal/mol); meanwhile, the free energy barriers of the deprotonation process of zwitterions in MCER-DEA and D001-PEI were 16.23 and 9.89 kcal/mol, respectively, indicating that D001-PEI chemically adsorbs CO2 and requires more energy than MCER-DEA chemical adsorption of CO2. D001-PEI is more conducive to the chemical adsorption of CO2. In addition, H2O molecules were incorporated on the polymer models to study the influence of humidity on the CO2 adsorption mechanism. The analysis revealed that the adsorption of CO2 slowed under humid conditions.

Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.

Coupling of nanostraws with diverse physicochemical perforation strategies for intracellular DNA delivery.

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.

Intracerebral hemorrhage-induced brain injury in mice: The role of peroxiredoxin 2-Toll-like receptor 4 inflammatory axis.

BACKGROUND: Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice. METHODS: First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed. RESULTS: Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits. CONCLUSIONS: Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.

Multi-Omics Analysis Revealed the AGR-FC.C3 Locus of Brassica napus as a Novel Candidate for Controlling Petal Color.

Variations in the petal color of Brassica napus are crucial for ornamental value, but the controlled loci for breeding remain to be unraveled. Here, we report a candidate locus, AGR-FC.C3, having conducted a bulked segregant analysis on a segregating population with different petal colors. Our results showed that the locus covers 9.46 Mb of the genome, harboring 951 genes. BnaC03.MYB4, BnaC03.MYB85, BnaC03.MYB73, BnaC03.MYB98, and BnaC03.MYB102 belonging to MYB TFs families that might regulate the petal color were observed. Next, a bulk RNA sequencing of white and orange-yellow petals on three development stages was performed to further identify the possible governed genes. The results revealed a total of 51 genes by overlapping the transcriptome data and the bulked segregant analysis data, and it was found that the expression of BnaC03.CCD4 was significantly up-regulated in the white petals at three development stages. Then, several novel candidate genes such as BnaC03.ENDO3, BnaC03.T22F8.180, BnaC03.F15C21.8, BnaC03.Q8GSI6, BnaC03.LSD1, BnaC03.MAP1Da, BnaC03.MAP1Db, and BnaC03G0739700ZS putative to controlling the petal color were identified through deeper analysis. Furthermo re, we have developed two molecular markers for the reported functional gene BnaC03.CCD4 to discriminate the white and orange-yellow petal colors. Our results provided a novel locus for breeding rapeseed with multi-color petals.

Application of bedside HINTS, ABCD2 score and truncal ataxia to differentiate cerebellar-brainstem stroke from vestibular neuritis in the emergency room.

BACKGROUND AND PURPOSE: Acute vestibular syndrome (AVS) typically manifests as isolated dizziness or vertigo with no apparent neurological impairments. However, distinguishing life-threatening stroke from innocuous peripheral vestibular lesions in the emergency room (ER) remains challenging. This study aimed to explore the ability of the head impulse-nystagmus-test of skew (HINTS) combined with truncal ataxia or ABCD2 score to differentiate stroke from peripheral vestibular disease in patients with AVS in the ER. METHODS: We prospectively recruited 121 patients with AVS from December 2022 to June 2023, 69 of whom presented with vestibular neuritis (VN) and the remaining with posterior circulation stroke (PCS). We analysed the HINTS results, truncal ataxia and ABCD2 score and compared the sensitivity and specificity among HINTS, truncal ataxia, ABCD2 score and their combinations using the McNemar test for paired samples. RESULTS: HINTS combined with grade 2-3 truncal ataxia achieved significantly higher sensitivity than that of isolated HINTS in differentiating PCS from VN (100% vs 88.5%, p=0.031). The specificity of HINTS plus grade 2-3 truncal ataxia did not significantly differ from that of isolated HINTS (p=0.125); however, the combination of ABCD2 score and HINTS did not improve the diagnostic accuracy. The sensitivity of ABCD2 score ≥4 plus grade 2-3 truncal ataxia was significantly higher than those of isolated ABCD2 score ≥4 or isolated grade 2-3 truncal ataxia (p=0.016 and p<0.001, respectively) and not significantly lower than that of isolated HINTS (p=0.508). CONCLUSION: Compared with the ABCD2 score, the truncal ataxia is of more valuable assistance to HINTS in differentiating PCS. Although the combination of ABCD2 score and truncal ataxia has a significant implication, it is not a replacement for HINTS.

Investigating the Antidepressant Mechanisms of Polygonum sibiricum Polysaccharides via Microglial Polarization.

Polygonum sibiricum, with its medicinal and edibility dual properties, has been widely recognized and utilized throughout Chinese history. As a kind of its effective component, Polygonum sibiricum polysaccharides (PSP) have been reported to be a promising novel antidepressant agent. Meanwhile, the precise mechanisms underlying its action remain elusive. The polarization state transition of microglia is intricately linked to neuroinflammation, indicating its crucial involvement in the pathophysiology of depression. Researchers are vigorously pursuing the exploration of this potential treatment strategy, aiming to comprehend its underlying mechanisms. Hence, the current study was designed to investigate the antidepressant mechanisms of PSP via Microglial M1/M2 Polarization, based on the lipopolysaccharide (LPS)-induced BV2 cell activation model. The results indicate that PSP significantly inhibited NO and LDH release and reduced ROS levels in LPS-induced BV2 cells. PSP could significantly reduce the protein expression level of Iba-1, decreased the mRNA levels of TNF-α, IL-1ß, and IL-6, and increased the mRNA level of IL-10. PSP also significantly reduced the protein expression level of CD16/32 and increased that of CD206, reduced the mRNA level and fluorescence intensity of iNOS, and increased those of Arg-1. However, PSP pretreatment reversed the alterations of the BDNF/TrkB/CREB and Notch/Hes1 pathways in LPS-induced BV2 cells. These results suggested that PSP exerted the anti-inflammatory effects by inhibiting M1 phenotype polarization and promoting microglia polarization toward the M2 phenotype, and its regulation of microglia M1/M2 polarization may be associated with modulating the BDNF/TrkB/CREB and Notch/Hes1 pathways.

Asymmetric response of transition metal cationic orbitals to applied electric field.

Understanding the quantum mechanical mechanisms underlying atomic/ionic interfacial processes and phenomena, particularly their dependence on the electronic orbital rearrangement of atoms/ions in an external electric field, remains a significant challenge. This study investigated the asymmetric response of transition metal (TM) cationic orbitals when subjected to an applied electric field. Quantum mechanical calculations were employed to quantify the newly formed hybrid orbitals and evaluate the corresponding orbital energies of the TM cations. Analysis of the quantitative contribution of asymmetric orbital hybridization to TM-surface interactions showed a significant change in orbital energy and increased effective charges of TM cations at the charged surface. This asymmetric response, induced by a negative external electric field generated from the structural charges of clay minerals (e.g., montmorillonite), repels electrons from the outer-shell orbital. This repulsion consequently increases the electron binding energy of the inner-shell orbitals, leading to new surface reactions, polarization-enhanced induction force, and polarization-induced covalent bonding between the TM cations and the charged surface. Our theoretical predictions regarding TM-clay mineral interactions are consistent with the experimental observations of TM cation adsorption. This finding has significant implications for the adsorptive removal of TM cations from wastewaters and for enhancing the catalytic efficiency of TM-surface catalysts. The unique physical and chemical characteristics exhibited by TMs at charged particle surfaces, resulting from their asymmetric response, can play pivotal roles in environmental and chemical engineering.

Association between the frailty index and readmission risk in hospitalised elderly Chinese patients: a retrospective cohort study.

OBJECTIVES: Frailty is a common and important concern of the ageing population. This study examined the association between the frailty index and negative outcomes of hospitalised elderly Chinese patients. DESIGN: Retrospective cohort study. SETTING: Geriatrics Department of Peking University First Hospital. PARTICIPANTS: 470 hospitalised elderly patients. MAIN OUTCOMES AND MEASURES: Frailty was measured using a 30-item deficit-accumulation frailty index. The outcomes were the hospitalisation duration and readmission. RESULTS: The frailty index was available for 470 patients: 72 (15.32%) were categorised as robust, 272 (57.87%) as prefrail and 126 (26.81%) as frail. The frail group had a longer hospital stay than the robust and prefrail groups. After adjustment for age, sex and cause of hospitalisation at baseline, frailty remained a strong independent risk factor for all-cause readmission and cardiocerebrovascular disease readmission (HR 2.41, 95% CI 1.49 to 3.91, p<0.001; HR 4.92, 95% CI 1.47 to 6.31, p<0.001, respectively). CONCLUSIONS: The frailty index predicted a longer length of stay and higher all-cause and cardiocerebrovascular disease readmission risk in hospitalised elderly patients.

Causal relationship between gut microbiome and sex hormone-binding globulin: A bidirectional two-sample Mendelian randomization study.

PROBLEM: Currently, there is a variety of evidence linking the gut microbiota to changes in sex hormones. In contrast, the causal relationship between SHBG, a carrier of sex hormones, and the gut microbiota is unclear. METHOD OF STUDY: Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between SHBG and the gut microbiome. Summary statistics of genome-wide association studies (GWASs) for the gut microbiome and SHBG were obtained from public datasets. Inverse-variance weighting (IVW), weighted median, weighted mode, MR-Egger and simple mode methods were used to operate the MR analysis. F-statistics and sensitivity analyses performed to evaluate bias and reliability. RESULTS: When we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, Coprobacter (PIVW = 2.01 × 10-6 ), Ruminococcus2 (PIVW = 3.40 × 10-5 ), Barnesiella (PIVW = 2.79 × 10-2 ), Actinobacteria (PIVW = 3.25 × 10-2 ) and Eubacterium fissicatena groups (PIVW = 3.64 × 10-2 ) were associated with lower SHBG levels; Alphaproteobacteria (PIVW = 1.61 × 10-2 ) is associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 9.75 × 10-3 ) and Defluviitaleaceae UCG011 (PIVW = 3.67 × 10-2 ) were associated with higher SHBG levels; Victivallaceae (PIVW = 2.23 × 10-2 ) was associated with lower SHBG levels. According to the results of reverse MR analysis, three significant causal effect of SHBG was found on gut microbiota. In males, Dorea (PIVW = 4.17 × 10-2 ) and Clostridiales (PIVW = 4.36 × 10-2 ) were associated with higher SHBG levels. In females, Lachnoclostridium (PIVW = 7.44 × 10-4 ) was associated with higherr SHBG levels. No signifcant heterogeneity of instrumental variables or horizontal pleiotropy was found in bidirectional two-sample MR analysis. CONCLUSIONS: This study may provide new insights into the causal relationship between the gut microbiome and sex hormone-binding protein levels, as well as new treatment and prevention strategies for diseases such as abnormal changes in sex hormones.

Antidepressant effects of Parishin C in chronic social defeat stress-induced depressive mice.

ETHNOPHARMACOLOGY RELEVANCE: Parishin C (Par), a prominent bioactive compound in Gastrodia elata Blume with little toxicity and shown neuroprotective effects. However, its impact on depression remains largely unexplored. AIM OF THE STUDY: This study aims to investigate the antidepressant effects of Par using a chronic social defeat stress (CSDS) mouse model and elucidate its molecular mechanisms. MATERIALS AND METHODS: The CSDS-induced depression mouse model was used to evaluate the therapeutic efficacy of Par. The social interaction test (SIT) and sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were conducted to assess the effects of Par on depressive-like behaviours. The levels of corticosterone, neurotransmitters (5-HT, DA and NE) and inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay (ELISA). Activation of a microglia was assessed by immunofluorescence labeling Iba-1. The protein expressions of NLRP3, ASC, caspase-1, and IL-6 verified by Western blot. RESULT: Oral administration of Par (4 and 8 mg/kg) and fluoxetine (10 mg/kg, administration significantly ameliorate depression-like behaviors induced by CSDS, as shown by the increase social interaction in SIT, increase sucrose preference in SPT and the decrease immobility in TST and FST. Par administration decreased serum corticosterone level and increased the 5-HT, DA and NE concentration in the hippocampus and prefrontal cortex. Furthermore, Par treatment suppressed microglial activation (Iba1) as well as reduced levels of IL-1ß, TNF-α, and IL-6) with decreased protein expressions of NLRP3, ASC, caspase-1, and IL-6. CONCLUSIONS: our study provides the first evidence that Par exerts antidepressant-like effects in mice with CSDS-induced depression. This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.

A Literature Review of the Pharmacological Effects of Jujube.

Jujube is a plant native to China that could be used in medicine and food. Its dried fruit is a superior herb commonly used in traditional Chinese medicine formulations for its calming effect and for nourishing the blood and strengthening the spleen and stomach. Jujube contains numerous active components including polysaccharides, phenols, and triterpene acids, which show a diverse array of pharmacological activities such as neuroprotection and the prevention and treatment of cardiovascular diseases. In this paper, the research status of jujube over the past two decades has been statistically evaluated. Meanwhile, by tracking the latest research advances, the pharmacological efficacy and molecular mechanisms of jujube are exhaustively expounded to provide specific and systematic references for further research on the pharmacological effects of jujube and its application in the food and pharmaceutical industries.

Fatal Case of Pneumocystis Jirovecii Pneumonia (PJP) During Treatment for Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient's oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.

Ginsenoside Rg1 Attenuates Chronic Sleep Deprivation-Induced Hippocampal Mitochondrial Dysfunction and Improves Memory by the AMPK-SIRT3 Pathway.

Ginsenoside Rg1 (Rg1) is the main bioactive ginseng component. This study investigates the effects of Rg1 on cognitive deficits triggered by chronic sleep deprivation stress (CSDS) and explores its underlying mechanisms. Rg1 effectively improved spatial working and recognition memory, as evidenced by various behavioral tests. RNA-sequence analysis revealed differential gene expression in the metabolic pathway. Treatment with Rg1 abrogated reductions in SOD and CAT activity, lowered MDA content, and increased Nrf2 and HO-1 protein levels. Rg1 administration alleviated hippocampal mitochondrial dysfunction by restoring normal ultrastructure and enhancing ATP activities and Mfn2 expression while regulating Drp-1 expression. Rg1 mitigated neuronal apoptosis by reducing the Bax/Bcl-2 ratio and the levels of cleaved caspase-3. Additionally, Rg1 upregulated AMPK and SIRT3 protein expressions. These findings suggest that Rg1 has potential as a robust intervention for cognitive dysfunction associated with sleep deprivation, acting through the modulation of mitochondrial function, oxidative stress, apoptosis, and the AMPK-SIRT3 axis.

Hemerocallis citrina Baroni ameliorates chronic sleep deprivation-induced cognitive deficits and depressive-like behaviours in mice.

Sleep deprivation (SD) is common during spaceflight. SD is known to cause cognitive deficits and depression, requiring treatment and prevention. Hemerocallis citrina Baroni (Liliaceae) is a perennial herb with antidepressant, antioxidant, antitumor, anti-inflammatory, and neuroprotective effects.The aim of our study was to investigate the effects of H. citrina extract (HCE) on SD-induced cognitive decline and depression-like behavior and possible neuroinflammation-related mechanisms. HCE (2 g/kg/day, i.g.) or vortioxetine (10 mg/kg/day, i.g.) were given to mice by oral gavage for a total of 28 days during the SD process. HCE treatment was found to ameliorate SD-induced impairment of short- and long-term spatial and nonspatial memory, measured using Y-maze, object recognition, and Morris water maze tests, as well as mitigating SD-induced depression-like behaviors, measured by tail suspension and forced swimming tests. HCE also reduced the levels of inflammatory cytokines (IL-1ß, IL-18, and IL-6) in the serum and hippocampus. Furthermore, HCE suppressed SD-induced microglial activation in the prefrontal cortex (PFC) and the CA1 and dentate gyrus (DG) regions of the hippocampus. HCE also inhibited the expression of phosphorylated NF-κB and activation of the NLRP3 inflammasome. In summary, our findings indicated that HCE attenuated SD-induced cognitive impairment and depression-like behavior and that this effect may be mediated by the inhibition of inflammatory progression and microglial activation in the hippocampus, as well as the down-regulation of NF-κB and NLRP3 signaling. The findings of these studies showingTthese results indicate that HCE exerts neuroprotective effects and are consistent with the findings of previous studies, suggesting that HCE is beneficial for the prevention and treatment of cognitive decline and depression in SD.

Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.

Percutaneous Coronary Intervention Offers Clinical Benefits to Diabetic Patients With Stable Chronic Total Occlusion.

Whether percutaneous coronary intervention for chronic total occlusion (CTO-PCI) in diabetic patients offers more benefits compared with initial medical therapy (CTO-MT) is unclear. In this study, diabetic patients with one CTO (clinical manifestations: stable angina or silent ischemia) were enrolled. Consecutively, enrolled patients (n = 1605) were assigned to different groups: CTO-PCI (1044 [65.0%]) and initial CTO-MT (561 [35%]). After a median follow-up of 44 months, CTO-PCI tended to be superior to initial CTO-MT in major adverse cardiovascular events (adjusted hazard-ratio [aHR]: .81, 95% conference-interval: .65-1.02) and significantly superior in cardiac death (aHR: .58 [.39-.87]) and all-cause death (aHR: .678[.473-.970]). Such superiority mainly attributed to a successful CTO-PCI. CTO-PCI tended to be performed in patients with younger age, good collaterals, left anterior descending branch CTO, and right coronary artery CTO. While, those with left circumflex CTO and severe clinical/angiographic situations were more likely to be assigned to initial CTO-MT. However, none of these variables influenced the benefits of CTO-PCI. Thus, we concluded that for diabetic patients with stable CTO, CTO-PCI (mainly successful CTO-PCI) offered patients survival benefits over initial CTO-MT. These benefits were consistent regardless of clinical/angiographic characteristics.

Effects of different chronic restraint stress periods on anxiety- and depression-like behaviors and tryptophan-kynurenine metabolism along the brain-gut axis in C57BL/6N mice.

Chronic restraint stress (CRS) is a widely used stimulus to induce anxiety- and depression-like behaviors, linked to alterations in tryptophan-kynurenine (TRP-KYN) metabolism in animals. This study assessed the effects of different CRS periods on anxiety- or depression-like behaviors and TRP-KYN metabolism along brain-gut axis in C57BL/6N mice. Results showed that one-week CRS decreased the open arm entries of mice in elevated plus maze and delayed latency of feeding in novelty suppressed feeding test. Four-week CRS reduced sucrose preference, increases forced swimming immobility time, and also induced anxiety-like behaviors of mice. UPLC-MS/MS analysis revealed decreased levels of the neurotoxic 3-hydroxykynurenine (3-HK) and quinolinic acid (QA), and an increase in the neuroprotective kynurenic acid (KA) in the hippocampus of one-week CRS mice; meanwhile, four-week CRS mice displayed a reduction in KA and increases in 3-HK and QA. In the colon, both one-week and four-week CRS mice exhibited significant reductions in 3-HK and QA, with a marked increase of KA exclusively in four-week CRS mice. Briefly, one-week CRS only induced anxiety-like behaviors with hippocampal neuroprotection in TRP-KYN metabolism, whereas four-week CRS caused anxiety- and depression-like behaviors with neurotoxicity. In the colon, during both CRS periods, KYN was metabolized in the direction of NAD+ production. However, four-week CRS triggered intestinal inflammation risk with increased KA. Summarily, slightly short-term stress has beneficial effects on mice, while prolonged chronic stress can lead to pathological changes. This study offers valuable insights into stress-induced emotional disturbances.

Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10-3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.