Association of TyG index with aortic valve calcification in valvular heart disease patients.

BACKGROUND: In recent years, triglyceride glucose (TyG) index, as a popular metabolic index, has been proposed as an alternative index of insulin resistance, and it has been proved to be associated with many cardiovascular diseases, but the relationship between it and aortic valve calcification is still unknown. METHODS: A total of 450 aortic valve disease patients were enrolled in this study, including 361 patients with aortic valve calcification (AVC) (calcification group) and 89 patients without (control group). According to the severity of AVC, patients with AVC included severe calcification, moderate calcification and low calcification. The TyG index was calculated based on fasting triglyceride and fasting blood glucose levels. RESULTS: The TyG index in the calcification group was significantly higher than that in the control group (P < .05), and with the increase of the degree of calcification, the TyG index showed an increasing trend. The univariate and multivariate logistic regression analysis showed TyG index has a high predictive value for the presence of AVC (OR (95% CI): 1.743 (1.036-2.933)) and severe AVC (OR (95% CI): 1.608 (1.143-2.262)). In assessing the predictive value of the TyG index distribution width for AVC, with the first quartile as a reference, the last quartile of the TyG index had significant predictive value for the presence of AVC and severe AVC. CONCLUSIONS: TyG index was significantly associated with the presence and severity of AVC, suggesting that TyG index may be a valid predictor of AVC.

Versatile Activated Carbon Fibers Derived from the Cotton Fibers Used as CO2 Solid-State Adsorbents and Electrode Materials.

Activated carbon has an excellent porous structure and is considered a promising adsorbent and electrode material. In this study, activated carbon fibers (ACFs) with abundant microporous structures, derived from natural cotton fibers, were successfully synthesized at a certain temperature in an Ar atmosphere and then activated with KOH. The obtained ACFs were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), elemental analysis, nitrogen and carbon dioxide adsorption-desorption analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and N2 adsorption-desorption measurement. The obtained ACFs showed high porous qualities and had a surface area from 673 to 1597 m2/g and a pore volume from 0.33 to 0.79 cm3/g. The CO2 capture capacities of prepared ACFs were measured and the maximum capture capacity for CO2 up to 6.9 mmol/g or 4.6 mmol/g could be achieved at 0 °C or 25 °C and 1 standard atmospheric pressure (1 atm). Furthermore, the electrochemical capacitive properties of as-prepared ACFs in KOH aqueous electrolyte were also studied. It is important to note that the pore volume of the pores below 0.90 nm plays key roles to determine both the CO2 capture ability and the electrochemical capacitance. This study provides guidance for designing porous carbon materials with high CO2 capture capacity or excellent capacitance performance.

Unveiling the detrimental vicious cycle linking skeletal muscle and COVID-19: A systematic review and meta-analysis.

OBJECTIVE: Skeletal muscle catabolism supports multiple organs and systems during severe trauma and infection, but its role in COVID-19 remains unclear. This study investigates the interactions between skeletal muscle and COVID-19. METHODS: The PubMed, EMbase, and The Cochrane Library databases were systematically searched from January 2020 to August 2023 for cohort studies focusing on the impact of skeletal muscle on COVID-19 prevalence and outcomes, and longitudinal studies examining skeletal muscle changes caused by COVID-19. Skeletal muscle quantity (SMQN) and quality (SMQL) were assessed separately. The random-effect model was predominantly utilized for statistical analysis. RESULTS: Seventy studies with moderate to high quality were included. Low SMQN/SMQL was associated with an increased risk of COVID-19 infection (OR = 1.62, p < 0.001). Both the low SMQN and SMQL predicted COVID-19-related mortality (OR = 1.53, p = 0.016; OR = 2.18, p = 0.001, respectively). Mortality risk decreased with increasing SMQN (OR = 0.979, p = 0.009) and SMQL (OR = 0.972, p = 0.034). Low SMQN and SMQL were also linked to the need for intensive care unit/mechanical ventilation, increased COVID-19 severity, and longer hospital stays. Significant skeletal muscle wasting, characterized by reduced volume and strength, was observed during COVID-19 infection and the pandemic. CONCLUSIONS: This study reveals a detrimental vicious circle between skeletal muscle and COVID-19. Effective management of skeletal muscle could be beneficial for treating COVID-19 infections and addressing the broader pandemic. These findings have important implications for the management of future virus pandemics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023395476.

Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.

AIMS: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo. METHODS: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole. Lysosomal staining was used to determination of lansoprazole on ABCB1-mediated lysosomal sequestration. Substrate accumulation and efflux assays, ATPase activity, and molecular docking were conducted to evaluate lansoprazole on ABCB1/G2 functions. Western blot and immunofluorescence were used to detect lansoprazole on ABCB1/G2 expression and subcellular localization. MDR nude mice models were established to evaluate the effects of lansoprazole on MDR in vivo. RESULTS: Lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects with substrate drugs in MDR cells. In vivo experiments demonstrated that lansoprazole attenuated ABCB1/G2-mediated MDR and exhibited synergistic effects that augmented the sensitivity of substrate anticancer drugs in ABCB1/G2-mediated settings without obvious toxicity. Lansoprazole impeded lysosomal sequestration mediated by ABCB1, leading to a substantial increase in intracellular accumulation of substrate drugs. The effects of lansoprazole were not attributable to downregulation or alterations in subcellular localization of ABCB1/G2. Lansoprazole promoted the ATPase activity of ABCB1/G2 and competitively bound to the substrate-binding region of ABCB1/G2. CONCLUSIONS: These findings present novel therapeutic avenues whereby the combination of lansoprazole and chemotherapeutic agents mitigates MDR mediated by ABCB1/G2 overexpression.

Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012.

BACKGROUND: An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. DESIGN, SETTING, PARTICIPANTS: Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer's Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in ß-diversity were analyzed using permutational analysis of variance. RESULTS: A total of 605 participants aged 60-69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (ß, 2.92; 95% CI, 1.01-4.84). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio, 2.35; 95% CI, 1.28-4.30) and were less likely to experience subjective memory changes (adjusted odds ratio, 0.43; 95% CI, 0.25-0.74). In addition, ß-diversity was statistically significant for the cognitive performance status based on DSST (P = 0.031) and subjective memory changes (P = 0.023). CONCLUSIONS: Oral microbial composition was associated with executive function and subjective memory changes among older adults among older U.S. adults in a nationally representative population sample. Oral dysbiosis is a potential biomarker or therapeutic target for cognitive decline. Further work is needed to elucidate the mechanisms underpinning the association between the oral microbiome and cognitive function.

Structure-activity relationship and mechanistic study of organotins as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases.

Organotins have been widely used in various industrial applications. This study investigated the structure-activity relationship as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD). Human KGN cell, pig, and rat testis microsomes were utilized to assess the inhibitory effects of 18 organotins on the conversion of pregnenolone to progesterone. Among them, diphenyltin, triethyltin, and triphenyltin exhibited significant inhibitory activity against human 3ß-HSD2 with IC50 values of 114.79, 106.98, and 5.40 µM, respectively. For pig 3ß-HSD, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin demonstrated inhibitory effects with IC50 values of 172.00, 100.19, 87.00, 5.75, and 1.65 µM, respectively. Similarly, for rat 3ß-HSD1, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin displayed inhibitory activity with IC50 values of 81.35, 43.56, 55.55, 4.09, and 0.035 µM, respectively. They were mixed inhibitors of pig and rat 3ß-HSD, while triphenyltin was identified as a competitive inhibitor of human 3ß-HSD2. The mechanism underlying the inhibition of organotins on 3ß-HSD was explored, revealing that they may disrupt the enzyme activity by binding to cysteine residues in the catalytic sites. This proposition was supported by the observation that the addition of dithiothreitol reversed the inhibition caused by all organotins except for triethyltin, which was partially reversed. In conclusion, this study provides valuable insights into the structure-activity relationship of organotins as inhibitors of human, pig, and rat gonadal 3ß-HSD. The mechanistic investigation suggests that these compounds likely exert their inhibitory effects through binding to cysteine residues in the catalytic sites.

The Effect of Sn-2 Palmitate on Blood Glucose, Lipids and Body Composition in Middle-Aged and Elderly Adults: A Randomized, Double-Blinded Controlled Trial.

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45-75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480).

Investigation of selenium and selenium species in Cardamine violifolia using in vitro digestion coupled with a Caco-2 cell monolayer model.

Inadequate Se intake can enhance vulnerability to certain health risks, with supplementation lessening these risks. This study investigated the bioavailability of Se and Se species in five Se compounds and in Se-rich Cardamine violifolia using in vitro digestion coupled with a Caco-2 cell monolayer model, which enabled the study of Se transport and uptake. Translocation results showed that SeCys2 and MeSeCys had high translocation rates in C. violifolia leaves (CVLs). The uptake rate of organic Se increased with time, and MeSeCys exhibited a higher uptake rate than that for SeCys2 and SeMet. The translocation mechanisms of SeMet, Se(IV), and Se(VI) were passive transport, whereas those of SeCys2 and MeSeCys were active transport. The bioavailability of organic Se was higher than that of inorganic Se, with a total Se bioavailability in CVLs of 49.11 %. This study would provide a theoretical basis for the application of C. violifolia in the functional food.

Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test.

BACKGROUND: Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath. METHODS: This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients' baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery). RESULTS: A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123. CONCLUSIONS: Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients' response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.

Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium.

Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.

Neurological complications during the Omicron COVID-19 wave in China: A cohort study.

BACKGROUND AND PURPOSE: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID-19) during the 2022 Omicron wave. METHODS AND ANALYSIS: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID-19-related new-onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. RESULTS: In all, 790 people were enrolled, of whom 436 were positive for COVID-19. Ninety-nine had new onset COVID-related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID-specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. CONCLUSION: New-onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large-scale treatment trial of people with COVID-19 infection presenting with neurological disorders is still needed.

Responses of root characteristics and nitrogen absorption and assimilation to different pH gradients of winter wheat at seedling stage.

Nitrogen (N) and rhizosphere pH are the two main factors restricting the growth of winter wheat (Triticum aestivum L.) in North China Plain. Soil nutrient availability is affected by soil acidity and alkalinity. In order to understand the effect of rhizosphere pH value on wheat nitrogen metabolism and the response of wheat growth to pH value at seedling stage, winter wheat varieties 'Aikang 58' (AK58) and 'Bainong 4199' (BN4199) were tested in hydroponics under three pH treatments (pH = 4.0, 6.5, and 9.0). The results showed that the accumulation of dry matter in root and above ground under pH 4.0 and pH 9.0 treatments was lower than that under pH 6.5 treatments, and the root/shoot ratio increased with the increase of pH value. Regardless of pH value, 'BN4199' had higher root dry weight, root length, root surface area, root activity and root tip than 'AK58'. Therefore, wheat that is tolerant to extreme pH is able to adapt to the acid-base environment by changing root characteristics. At pH 4.0, the net H+ outflow rate of wheat roots was significantly lower than that of the control group, and the net NO3- flux of wheat roots was also low. The net H+ outflow occurred at pH 6.5 and 9.0, and at the same time, the net NO3- flux of roots also increased, and both increased with the increase of pH. The activity of nitrate reductase (NR) in stem of pH 9.0 treatment was significantly higher than that of other treatments, while the activity of glutamine synthetase (GS) in root and stem of pH 6.5 treatment was significantly higher than that of other treatments. Under pH 4.0 and pH 9.0 treatments, the activities of NR and GS in 'BN4199' were higher than those in 'AK58', The root respiration of 'BN4199' was significantly higher than that of 'AK58' under pH 4.0 and pH 9.0 treatment, and 'BN4199' had higher NO3- net flux, key enzyme activity of root nitrogen metabolism and root respiration. Therefore, we believe that 'BN4199' has strong resistance ability to extreme pH stress, and high root/shoot ratio and strong root respiration can be used as important indicators for wheat variety screening adapted to the alkaline environment at the seedling stage.

Transcriptome Analysis Reveals Fruit Quality Formation in Actinidia eriantha Benth.

Actinidia chinensis Planch. is a fruit tree originating from China that is abundant in the wild. Actinidia eriantha Benth. is a type of A. chinensis that has emerged in recent years. The shape of A. eriantha is an elongated oval, and the skin is covered with dense, non-shedding milk-white hairs. The mature fruit has flesh that is bright green in colour, and the fruit has a strong flavour and a grass-like smell. It is appreciated for its rich nutrient content and unique flavour. Vitamin C, sugar, and organic acids are key factors in the quality and flavour composition of A. eriantha but have not yet been systematically analysed. Therefore, we sequenced the transcriptome of A. eriantha at three developmental stages and labelled them S1, S2, and S3, and comparisons of S1 vs. S2, S1 vs. S3, and S2 vs. S3 revealed 1218, 4019, and 3759 upregulated differentially expressed genes and 1823, 3415, and 2226 downregulated differentially expressed genes, respectively. Furthermore, the upregulated differentially expressed genes included 213 core genes, and Gene Ontology enrichment analysis showed that they were enriched in hormones, sugars, organic acids, and many organic metabolic pathways. The downregulated differentially expressed genes included 207 core genes, which were enriched in the light signalling pathway. We further constructed the metabolic pathways of sugars, organic acids, and vitamin C in A. eriantha and identified the genes involved in vitamin C, sugar, and organic acid synthesis in A. eriantha fruits at different stages. During fruit development, the vitamin C content decreased, the carbohydrate compound content increased, and the organic acid content decreased. The gene expression patterns were closely related to the accumulation patterns of vitamin C, sugars, and organic acids in A. eriantha. The above results lay the foundation for the accumulation of vitamin C, sugars, and organic acids in A. eriantha and for understanding flavour formation in A. eriantha.

A Hyperflexible Electrode Array for Long-Term Recording and Decoding of Intraspinal Neuronal Activity.

Neural interfaces for stable access to the spinal cord (SC) electrical activity can benefit patients with motor dysfunctions. Invasive high-density electrodes can directly extract signals from SC neuronal populations that can be used for the facilitation, adjustment, and reconstruction of motor actions. However, developing neural interfaces that can achieve high channel counts and long-term intraspinal recording remains technically challenging. Here, a biocompatible SC hyperflexible electrode array (SHEA) with an ultrathin structure that minimizes mechanical mismatch between the interface and SC tissue and enables stable single-unit recording for more than 2 months in mice is demonstrated. These results show that SHEA maintains stable impedance, signal-to-noise ratio, single-unit yield, and spike amplitude after implantation into mouse SC. Gait analysis and histology show that SHEA implantation induces negligible behavioral effects and Inflammation. Additionally, multi-unit signals recorded from the SC ventral horn can predict the mouse's movement trajectory with a high decoding coefficient of up to 0.95. Moreover, during step cycles, it is found that the neural trajectory of spikes and low-frequency local field potential (LFP) signal exhibits periodic geometry patterns. Thus, SHEA can offer an efficient and reliable SC neural interface for monitoring and potentially modulating SC neuronal activity associated with motor dysfunctions.

The initial treatment in convulsive status epilepticus in China: A multi-center observational study.

OBJECTIVE: To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. METHODS: In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay. RESULTS: Three-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16-92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes. SIGNIFICANCE: Non-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.

First add-on lacosamide treatment in children with focal epilepsy in China: A multi-centre real-life cohort study.

AIM: To assess the effectiveness and safety of lacosamide (LCM) as the first add-on therapy for children with focal epilepsy at multiple centres in China. METHOD: Children aged 4-16 years with focal epilepsy from 13 epilepsy centres were included in this study. All patients were treated with LCM as the first add-on treatment and followed up for 26 weeks. The seizure frequency, seizure-free rate, ≥50% response rate, retention rate, and incidence of adverse drug reactions after the addition of LCM were analysed. RESULTS: Ninety-nine children (58 males; aged 4-16 years; mean age 8.51 ± 2.95 years) were enroled. The mean age at first seizure was 5.74 ± 3.12 years. All patients were administered LCM as the first add-on treatment for focal epilepsy. Twenty-eight patients (28/99, 28.28%) did not experience seizures during the follow-up period. The ≥50% response rates were 80.81% (80/99), 93.88% (92/98), 98.98% (97/98), and 100.0% (98/98) at 6 weeks (visit two), 10 weeks (visit three), 18 weeks (visit four), and 26 weeks (visit five), respectively, compared to that at baseline (visit one). The intelligence scores decreased in 12 participants, remained unchanged in 64, and increased in 16. Adverse events occurred in three participants during the trial, all of which were mild. INTERPRETATION: LCM was effective as the first add-on therapy in this real-life multi-centre study of a paediatric population with focal epilepsy. Further prospective studies with long-term follow-up periods are needed to confirm the effectiveness and tolerability of LCM.

In vitro antibiofilm and bacteriostatic activity of diacerein against Enterococcus faecalis.

Enterococcus faecalis is one of the main pathogens that causes hospital-acquired infections because it is intrinsically resistant to some antibiotics and often is capable of biofilm formation, which plays a critical role in resisting the external environment. Therefore, attacking biofilms is a potential therapeutic strategy for infections caused by E. faecalis. Current research indicates that diacerein used in the treatment of osteoarthritis showed antimicrobial activity on strains of gram-positive cocci in vitro. In this study, we tested the MICs of diacerein using the broth microdilution method, and successive susceptibility testing verified that E. faecalis is unlikely to develop resistance to diacerein. In addition, we obtained a strain of E. faecalis HE01 with strong biofilm-forming ability from an eye hospital environment and demonstrated that diacerein affected the biofilm development of HE01 in a dose-dependent manner. Then, we explored the mechanism by which diacerein inhibits biofilm formation through qRT-PCR, extracellular protein assays, hydrophobicity assays and transcriptomic analysis. The results showed that biofilm formation was inhibited at the initial adhesion stage by inhibition of the expression of the esp gene, synthesis of bacterial surface proteins and reduction in cell hydrophobicity. In addition, transcriptome analysis showed that diacerein not only inhibited bacterial growth by affecting the oxidative phosphorylation process and substance transport but also inhibited biofilm formation by affecting secondary metabolism, biosynthesis, the ribosome pathway and luxS expression. Thus, our findings provide compelling evidence for the substantial therapeutic potential of diacerein against E. faecalis biofilms.

The Application of Biomedicine in Chemodynamic Therapy: From Material Design to Improved Strategies.

Chemodynamic therapy (CDT) has garnered significant interest as an innovative approach for cancer treatment, owing to its notable tumor specificity and selectivity, minimal systemic toxicity and side effects, and absence of the requirement for field stimulation during treatment. This treatment utilizes nanocatalytic medicines containing transitional metals to release metal ions within tumor cells, subsequently initiating Fenton and Fenton-like reactions. These reactions convert hydrogen peroxide (H2O2) into hydroxyl radical (•OH) specifically within the acidic tumor microenvironment (TME), thereby inducing apoptosis in tumor cells. However, insufficient endogenous H2O2, the overexpressed reducing substances in the TME, and the weak acidity of solid tumors limit the performance of CDT and restrict its application in vivo. Therefore, a variety of nanozymes and strategies have been designed and developed in order to potentiate CDT against tumors, including the application of various nanozymes and different strategies to remodel TME for enhanced CDT (e.g., increasing the H2O2 level in situ, depleting reductive substances, and lowering the pH value). This review presents an overview of the design and development of various nanocatalysts and the corresponding strategies employed to enhance catalytic drug targeting in recent years. Additionally, it delves into the prospects and obstacles that lie ahead for the future advancement of CDT.

High-Performance Lithium-Sulfur Batteries via Molecular Complexation.

Beyond lithium-ion technologies, lithium-sulfur batteries stand out because of their multielectron redox reactions and high theoretical specific energy (2500 Wh kg-1). However, the intrinsic irreversible transformation of soluble lithium polysulfides to solid short-chain sulfur species (Li2S2 and Li2S) and the associated large volume change of electrode materials significantly impair the long-term stability of the battery. Here we present a liquid sulfur electrode consisting of lithium thiophosphate complexes dissolved in organic solvents that enable the bonding and storage of discharge reaction products without precipitation. Insights garnered from coupled spectroscopic and density functional theory studies guide the complex molecular design, complexation mechanism, and associated electrochemical reaction mechanism. With the novel complexes as cathode materials, high specific capacity (1425 mAh g-1 at 0.2 C) and excellent cycling stability (80% retention after 400 cycles at 0.5 C) are achieved at room temperature. Moreover, the highly reversible all-liquid electrochemical conversion enables excellent low-temperature battery operability (>400 mAh g-1 at -40 °C and >200 mAh g-1 at -60 °C). This work opens new avenues to design and tailor the sulfur electrode for enhanced electrochemical performance across a wide operating temperature range.