A facile solid-state approach is employed to synthesize a novel magnetoplumbite-type oxide of NdMgAl11O19, which integrates spinel-stacking layers (MgAl2O4) with Nd-O6 mirror plane structures. The resulting NdMgAl11O19 exhibits remarkable catalytic activity and conversion efficiency during the sulfur reduction reaction (SRR) in lithium-sulfur batteries. By employing the 2D projection mapping technique of in situ confocal Raman spectroscopy and electrochemical technique, it is discovered that the exposed mirror plane structure of Nd-O6 can effectively suppress the undesiring disproportionation reaction (S8 2-âS6 2-+1/4 S8) of long-chain lithium polysulfides at the initial stages of sulfur reduction, thereby promoting the positive process of sulfur to lithium sulfide. This not only mitigates the issue of sulfur shuttle loss but also significantly improve the kinetics of the conversion process. Leveraging these advantages, the NdMgAl11O19/S cathode delivered an impressive initial capacity of up to 1398 mAh g-1 at an electrolyte/sulfur (E/S) ratio of 5.1 µL mg-1 and a sulfur loading of 2.3 mg cm-2. Even when the sulfur loading is increased to 10.02 mg cm-2, the cathode retained a reversible areal capacity of 10.01 mAh cm-2 after 200 cycles. This mirror engineering strategy provides valuable and universal insights into enhancing the efficiency of cathodes in Li-S battery.
Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in Front Psychiatry 2022; 13:1001484.
Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.
Technological innovation is a critical element of economic and environmental sustainability; thus, the promotion of technological innovation in the economy has gained an apex among policy makers. The study's impetus is to measure the effect of investments in information and communication technology (ICT), education, and political stability on technical innovation in BRI countries for 2004-2020. In the process of documenting the empirical nexus through the implementation of novel panel techniques commonly known as Dynamic Seemingly Unrelated Regressions (SUR), continuously updated fully modified" (Cup-FM) and continuously updated bias-corrected (Cup-BC). The results of the slope of heterogeneity, cross-sectional dependency test, and panel cointegration test have revealed the presence of heterogeneity, all the research variables possessed certain common dynamics, and, most importantly presence of long-run association. The study documented the coefficients of ICT, education and Political stability are positive and statistically significant, indicating a contributory effect in fostering technological innovation in BRI nations. The findings emphasize the importance of upholding political stability, directing resources toward education, and fostering an environment that encourages innovation through the integration of information and communication technology (ICT). The study also highlights how critical it is to bring in FDI and use it to your advantage in order to boost tech development and the economy.
INTRODUCTION: Chronic neck pain (CNP) is a global public health problem, with high prevalence and absenteeism rates. Central sensitization (CS) as a basis for chronic pain may play an essential role in its development and progression. It is often comorbid with low conditioned pain modulation (CPM) effects, cognitions, and psychological problems. OBJECTIVES: The purposes of this study were to (1) explore the relationship between pain-related cognitions and psychological factors, CPM effects, and the central sensitization inventory (CSI) scores; and (2) determine whether cognitions and psychological factors can predict CSI scores and CPM effects in individuals with CNP. METHODS: Fifty-four individuals with CNP were recruited for this cross-sectional study. The following outcome measures were evaluated: The CSI (screening tool) was compared with the cold pressor test (CPT), which was the psychophysical test used to assess the CPM; neck pain intensity using the visual analogue scale (VAS), as well as pain-related cognitions (including kinesiophobia and pain catastrophization) and psychological states (including anxiety and depression) using self-report questionnaires. RESULTS: CSI score was not associated with the CPM effect (r = 0.257, p > 0.05), and no cognitions or psychological factors were associated with CPM (p > 0.05), but CSI score was moderately positively correlated with kinesiophobia (r = 0.554, p < 0.01), lowly positively correlated with pain catastrophization (r = 0.332, p = 0.017) and anxiety (r = 0.492, p < 0.01), but not depression (r = 0.207, p = 0.132). Multiple linear regression analysis showed that kinesiophobia (B = 1.308, p < 0.01) and anxiety (B = 1.806, p = 0.02) were significant positive predictors of CSI score. CONCLUSIONS: The findings confirm some of our hypotheses. Accordingly, the findings inferred that the CSI does not seem to respond to CPM effect in patients with CNP effectively. In addition, CSI score was associated with cognitions and psychological factors, of which kinesiophobia and anxiety were effective predictors. In clinical practice, pain-related cognitions and psychological factors should be fully considered to manage neck pain efficiently.
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (n - 6) PUFAs and low levels of omega-3 (n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.
Colorectal Neoplasms , Inflammation , Oxylipins , Humans , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/pathology , Oxylipins/metabolism , Inflammation/metabolism , Animals , Fatty Acids, Omega-6/metabolism , Fatty Acids, Omega-6/therapeutic use
BACKGROUND: Previous studies had reported depression symptoms and TG/HDLC ratio may share pathophysiological pathway. The aim was to investigate the combined effects of depression symptoms and TG/HDL-C ratio on the risk of CMM. METHODS: This cohort study extracted data from 2011 to 2018 of CHARLS. The CMM event occurred from 2013 to 2018, defined as suffering from more than one of stroke, cardiac events, and diabetes mellitus. Cox proportional hazards regression models were used to assess the association between the baseline combined effects of depression symptoms and TG/HDL-C ratio with incidence of CMM, stroke, cardiac events, and diabetes mellitus. RESULTS: A total of 8349 participants (3966 men and 4383 women) were included in the study, with a mean age of 58.5 years. During a 7-year follow-up survey, 370 (4.43 %) participants developed CMM. Compared to individuals with no depression symptoms and low TG/HDLC ratio, the multivariable-adjusted HRs (95%CI) for the new-onset CMM for patients with the depression symptoms alone, high TG/HDLC ratio alone, and depression symptoms and high TG/HDLC ratio were 1.37 (95 % CI = 0.95-1.98), 1.62 (95 % CI = 1.22-2.14), 1.94 (95 % CI = 1.39-2.72), respectively (P < 0.001). LIMITATIONS: Firstly, potential confounding factors such as dietary intake and nutrition were not collected at the time of study design. Secondly, exposure to the outcome was self-reported, which may cause recall bias or misclassification. Finally, the population was aged ≥45 years, so the results cannot be generalized to all age groups. CONCLUSION: Our findings indicated that patients with depression and high TG/HDLC ratio had a higher risk of developing CMM.
Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.
Flavonoids , Glycolysis , Ovarian Neoplasms , Propiophenones , S-Phase Kinase-Associated Proteins , Ubiquitination , Propiophenones/pharmacology , S-Phase Kinase-Associated Proteins/metabolism , S-Phase Kinase-Associated Proteins/genetics , Flavonoids/pharmacology , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Glycolysis/drug effects , Animals , Signal Transduction/drug effects , Cadherins/metabolism , Carcinogenesis/drug effects , Antigens, CD/metabolism , Hexokinase/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-akt/metabolism , Mice , Phytotherapy , Mice, Nude , Antineoplastic Agents, Phytogenic/pharmacology
BACKGROUND AND HYPOTHESIS: Previous studies have found that both physical inactivity and poor sleep are deleteriously associated with severe mental illness (SMI). The aim of current study was to investigate the joint association of physical activity (PA) and sleep with late-onset SMI (schizophrenia and bipolar disorder) risk. STUDY DESIGN: A total of 340 187 (for schizophrenia)/340 239 (for bipolar disorder) participants without schizophrenia or bipolar disorder from the UK Biobank were included. Baseline PA levels were categorized as high, intermediate, and low according to the total volume of PA. Sleep was categorized into healthy, intermediate, and poor according to an established composited sleep score of chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. We derived 9 PA-sleep combinations, accordingly. STUDY RESULTS: After an average follow-up of 13.2 years, 814 participants experienced schizophrenia and 846 participants experienced bipolar disorder. Both low PA level, intermediate, and poor sleep were independently associated with increased risk of SMI. PA level and sleep had additive and multiplicative interactions on SMI risk. Compared to those with high PA level and healthy sleep, individuals with low PA and poor sleep had the highest risk of SMI (hazard ratio: 1.95; 95% CI: 1.02-3.70, Pâ <â .001) for schizophrenia; (hazard ratio: 3.81; 95% CI: 2.35-6.15) for bipolar disorder. A higher PA level may attenuate the detrimental effects of poor sleep. CONCLUSION: Both low PA and poor sleep was associated with increasing risk of late-onset SMI. Those with low PA and poor sleep had the highest risk of late-onset SMI, suggesting likely synergistic effects. Our findings supported the need to target both PA and sleep behaviors in research and clinical practice.
Objective: To assess the effectiveness of myofascial release (MFR) techniques on the intensity of headache pain and associated disability in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. Design: A systematic review and meta-analysis. Methods: Eight databases were searched on September 15, 2023, including PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, Embase, CNKI, and Wanfang Database. The risk of bias was evaluated utilizing the Cochrane Risk of Bias 2 (RoB 2) tool. Results: Pooled results showed that MFR intervention significantly reduces pain intensity [SMD = -2.01, 95% CI (-2.98, -1.03), I2 = 90%, P < 0.001] and improves disability [SMD = -1.3, 95% CI (-1.82, -0.79), I2 = 74%, P < 0.001]. Subgroup analysis based on the type of headache revealed significant reductions in pain intensity for CGH [SMD = -2.01, 95% CI (-2.73, -1.29), I2 = 63%, P < 0.001], TTH [SMD = -0.86, 95% CI (-1.52, -0.20), I2 = 50%, P=0.01] and migraine [SMD = -6.52, 95% CI (-8.15, -4.89), P < 0.001] and in disability for CGH [SMD = -1.45, 95% CI (-2.07, -0.83), I2 = 0%, P < 0.001]; TTH [SMD = -0.98, 95% CI (-1.32, -0.65), I2 = 0%, P < 0.001] but not migraine [SMD = -2.44, 95% CI (-6.04, 1.16), I2 = 97%, P=0.18]. Conclusion: The meta-analysis results indicate that MFR intervention can significantly alleviate pain and disability in TTH and CGH. For migraine, however, the results were inconsistent, and there was only moderate quality evidence of disability improvement for TTH and CGH. In contrast, the quality of other evidence was low or very low.
Migraine Disorders , Post-Traumatic Headache , Tension-Type Headache , Humans , Post-Traumatic Headache/therapy , Myofascial Release Therapy , Migraine Disorders/therapy , Headache , Tension-Type Headache/therapy , Pain
Candida albicans is the most common fungal pathogen associated with human opportunistic infections. Invasive infections caused by C. albicans are becoming increasingly serious. However, with the rising incidence of fungal infection, many fungi are resistant to commonly used drugs. Therefore, there is an urgent need for exploring new anti-fungal drugs that fungi are not resistant to. A series of novel azole derivatives linked to indole/indoline moieties were prepared, and in vitro antifungal activity evaluated. All compounds combined with FLC showed excellent activity against drug-resistant C. albicans with low toxicity. A preliminary mechanistic study indicated that S1 combined with FLC could inhibit the formation of C. albicans biofilms as well as destroy the integrity of cell-membrane structure and mitochondrial function. S1 could be considered a new fungal agent for further study.
OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.
Blood Pressure , Ischemic Stroke , Humans , Male , Female , Ischemic Stroke/physiopathology , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Aged , Blood Pressure/physiology , Time Factors , Middle Aged , Risk Factors , Prognosis , Hypertension/physiopathology , Hypertension/complications , Risk Assessment/methods , Aged, 80 and over , Blood Pressure Monitoring, Ambulatory/methods
Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.
Cytokines , Dermatitis, Atopic , Macrophages , NF-kappa B , Th2 Cells , Xanthones , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/immunology , Xanthones/pharmacology , Xanthones/therapeutic use , Animals , NF-kappa B/metabolism , Th2 Cells/immunology , Th2 Cells/drug effects , Cytokines/metabolism , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Mice, Inbred BALB C , Signal Transduction/drug effects , Humans , Male , Thymic Stromal Lymphopoietin , Immunoglobulin E/metabolism , Skin/drug effects , Skin/pathology , Skin/immunology , Skin/metabolism
Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances. IMPORTANCE: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.
Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Gastrointestinal Microbiome/drug effects , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Mice , Male , Diet, High-Fat/adverse effects , Dysbiosis/drug therapy , Dysbiosis/microbiology , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Bile Acids and Salts/metabolism , Fatty Acids, Volatile/metabolism , Lipid Metabolism/drug effects , Signal Transduction/drug effects , Plant Extracts
In this work, we synthesized a series of indole derivatives to cope with the current increasing fungal infections caused by drug-resistant Candida albicans. All compounds were evaluated for antifungal activities against Candida albicans in vitro, and the structure-activity relationships (SARs) were analyzed. The results indicated that indole derivatives used either alone or in combination with fluconazole showed good activities against fluconazole-resistant Candida albicans. Further mechanisms studies demonstrated that compound 1 could inhibit yeast-to-hypha transition and biofilm formation of Candida albicans, increase the activity of the efflux pump, the damage of mitochondrial function, and the decrease of intracellular ATP content. In vivo studies, further proved the anti-Candida albicans activity of compound 1 by histological observation. Therefore, compound 1 could be considered as a novel antifungal agent.
Candida albicans , Fluconazole , Fluconazole/pharmacology , Biofilms , Antifungal Agents , Structure-Activity Relationship , Indoles/pharmacology , Microbial Sensitivity Tests
BACKGROUND: Proprioceptive function assessment is crucial in clinical practice for patients with chronic non-specific neck pain (CNNP) as it is a major issue affecting their condition. PURPOSE: To verify the reliability and validity of baiobit sensor in measuring the neck proprioceptive function of CNNP patients. METHODS: Fifty-three CNNP patients were recruited (36 females, 17 males; age range 21-60 years) and were assessed for cervical joint position error by two blinded raters using the Baiobit sensor and laser pointer devices. The second measurement was conducted by the same rater 48 h later. Intra and inter-rater reliability of the Baiobit sensor was evaluated using the intra-class correlation coefficient (ICC), while the validity of the Baiobit sensor was established using the Spearman correlation coefficient. RESULTS: The Baiobit sensor demonstrated moderate to excellent intra-rater reliability in flexion, extension, left lateral flexion, right lateral flexion, and right rotation (ICCs=0.71â¼0.85, 95 %CIs: 0.50â¼0.91), left-rotation shows poor to good intra-rater reliability (ICC=0.56, 95 %CI: 0.25â¼0.75). The Baiobit sensor also demonstrated moderate to excellent inter-rater reliability in flexion, extension, left lateral flexion, right lateral flexion, and right rotation (ICCs=0.80â¼0.88, 95 %CIs: 0.65â¼0.91), left-rotation shows poor to good intra-rater reliability (ICC=0.59, 95 %CI: 0.29â¼0.76). Validity analysis showed that the Baiobit sensor had a range of low to high validity (r = 0.46â¼0.88) for measuring cervical proprioception function, with lower validity observed in the left flexion direction. The Baiobit showed good absolute reliability with low SEM and MDC90 values (0.35°â¼2.42°). CONCLUSION: The new device could be used as an alternative tool to evaluate neck proprioception.
Neck Pain , Wearable Electronic Devices , Male , Female , Humans , Young Adult , Adult , Middle Aged , Reproducibility of Results , Range of Motion, Articular , Neck Pain/diagnosis , Proprioception
With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.
Candidiasis , Ruthenium , Humans , Animals , Mice , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Fluconazole/pharmacology , Fluconazole/therapeutic use , Candida albicans , Ruthenium/pharmacology , Candidiasis/drug therapy , Microbial Sensitivity Tests
AIMS: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored. METHODS AND RESULTS: In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml-1 for AgNPs, 2.3 ± 5.1 µg ml-1 for AgNO3, and 25.1 ± 48.3 µg ml-1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6-20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment. CONCLUSION: We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.
Anti-Bacterial Agents , Carbapenems , Imipenem , Klebsiella pneumoniae , Metal Nanoparticles , Microbial Sensitivity Tests , Silver , Imipenem/pharmacology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Silver/pharmacology , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Klebsiella Infections/microbiology , Klebsiella Infections/drug therapy , Humans , Carbapenem-Resistant Enterobacteriaceae/drug effects , Carbapenem-Resistant Enterobacteriaceae/genetics , Drug Resistance, Bacterial/genetics
INTRODUCTION: At a rate of more than 30% annually, neck pain is a very prevalent musculoskeletal ailment that is second only to low back pain as the most common cause of disability. Most occurrences of neck pain are nonspecific. Telerehabilitation is regarded as a potentially effective healthcare approach in this setting. This review aims to evaluate how a telerehabilitation-based intervention affected individuals with nonspecific neck pain (NNP) in terms of pain and disability. METHODS: PubMed, Web of Science, Scopus, Embase, MEDLINE, Cochrane library, ClinicalTrials.gov, CNKI, and WanFang were consulted from inception to September 2023, with the inclusion of randomized controlled trials only. The experimental data were meta-analyzed using RevMan 5.3. RESULTS: The meta-analysis contained eight studies; there was no significant difference in pain improvement in patients with NNP by telerehabilitation compared to conventional care (SMD = -0.10, 95% CI: -0.48 to 0.28), but there was a significant effect on disability improvement (SMD = -0.41, 95% CI: -0.78 to -0.03). Telerehabilitation demonstrated more significant improvements in pain (SMD = -1.16, 95% CI: -1.99 to -0.32) and disability (MD = -3.78, 95% CI: -5.29 to -2.27) compared to minimal or no intervention. DISCUSSION: This study emphasizes the potential benefits of employing telerehabilitation in patients with NNP, especially in reducing pain intensity and improving disability. But additional study is required to fully grasp the potential of telerehabilitation in this field.
