Deletion of glycosyltransferase galE impairs the InlB anchoring and pathogenicity of Listeria monocytogenes.

Listeria monocytogenes (L. monocytogenes) is a foodborne intracellular pathogen that causes serious disease in both humans and animals. InlB is the major internalin protein of L. monocytogenes, which anchors to the bacterial surface and mediates its invasion into various host cells. Recent studies have shown that galactosylation of the cell wall polymer wall teichoic acid (WTA) is essential for InlB anchoring on the cell surface of L. monocytogenes serotype 4b strains. Galactosylation of WTA is exerted by the coordinated action of several glycosyltransferases, including GalU, GalE, GtcA, GttA, and GttB. Among these glycosyltransferases, GttA and GttB are specific to serotype 4b strains, whereas GalE, GalU, and GtcA are conserved across all serotypes. The role of GalE in InlB anchoring and L. monocytogenes pathogenicity remains unclear. In this study, we deleted the galE gene, which is involved in galactosylation, from L. monocytogenes strain ScottA. We found that galE deletion reduced InlB anchoring, weakened bacterial adhesion and invasion of Caco-2 cells (human colorectal adenocarcinoma cells) and MGC803 cells (human gastric carcinoma cells), increased phagocytosis but decreased proliferation in RAW264.7 cells (mouse mononuclear macrophage leukaemia cells), and decreased bacteria load, mortality, and tissue damage in infected mice. Taken together, galE deletion significantly reduced the anchoring of InlB and weakened the pathogenicity of L. monocytogenes. This finding provides new insights into the correlation between cell wall modification and pathogenicity of L. monocytogenes.

Redox Oxygen Species-Responsive Nanotheranostics with Dual-Channel Fluorescent Turn-On for Early Diagnosis and Targeted Therapy of Alzheimer's Disease.

Current diagnosis and treatment strategies mainly focus on the pathologies of the mid-to-late stage of AD (Alzheimer's disease), with clinical outcomes that are far from ideal. Herein, we developed the ROS (reactive oxygen species)-responsive brain neuronal targeting nanotheranostic platforms that possess the dual-channel fluorescent "turn-on" properties and release drugs in AD neurons in response to ROS, thereby simultaneously facilitating the diagnosis and therapy of early AD. Through the modification of acetylcholine receptor targeting RVG29 peptide, the nanotheranostics penetrated BBB and accumulated into diseased neurons in an intact form, consequently maximizing the diagnostic and therapeutic performance. The anti-oxidative drug baicalein conjugated onto the surface of nanotheranostics via ROS-cleavable boronate ester linkage rapidly released for ROS scavenging, while the encapsulated fluorophores turned on their fluorescence for AD diagnosis upon microenvironment stimuli. This nanotheranostic strategy exhibited highly sensitivity with a ROS detection limit of up to 100 µm and accurately early detection of ROS in 3×Tg AD mice at 6 months of age in vivo. In addition, it could also rescue memory defects, scavenge oxidative stress, attenuate neuroinflammation and enhance neuroprotective effect in 3×Tg AD mice. This work opens up a promising and smart strategy for early diagnosis and therapy in neurodegenerative disease.

Comparative analysis of SARC-F-EBM, Ishii test, and six other screening tools for sarcopenia in Chinese community-dwelling older adults: a cross-sectional diagnostic study.

To assess the relative performance of simple screening methods for sarcopenia in Chinese community-dwelling older adults. Data of older adults aged ≥ 60 were collected through a cross-sectional investigation. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. The accuracy of screening methods was evaluated using sensitivity, specificity, receiver operating characteristic (ROC) curves and area under the ROC curves (AUC). The AUC value greater than 0.8 represented the good screening ability. A total of 918 older adults (44.3% men, mean age 70.4 ± 6.5 years) were included in this study. The overall prevalence rates of possible sarcopenia, confirmed sarcopenia, and severe sarcopenia were 59.5%, 12.8%, and 5.9%, respectively. In men, the SARC-F-EBM and Ishii tests indicated good screening capabilities for confirmed sarcopenia, with an AUC of 0.81 (95% CI: 0.77-0.85) and 0.80 (95% CI: 0.76-0.84), respectively. In women, the highest AUC was also achieved using the SARC-F-EBM at 0.79 (95% CI: 0.75-0.82), followed by the Ishii test at 0.77 (95% CI: 0.74-0.81), showing the moderate efficacy. A ranking diagram showed that SARC-F-EBM was most likely to be considered the best method for diagnosing sarcopenia in terms of AUC and sensitivity, regardless of sex. We recommend the SARC-F-EBM for sarcopenia screening in community-dwelling Chinese older adults when respondents are able to answer the questionnaire accurately; otherwise, the Ishii test consisting entirely of objective measures could be used.

DNA methylation inhibitors adverse reaction characteristic analysis: a descriptive analysis from WHO-VigiAccess.

Introduction: DNA methylation inhibitors (azacitidine, decitabine) have revolutionized the treatment dilemma of myelodysplastic syndromes (MDS), a group of malignant hematopoietic disorders. This study evaluates the adverse drug reactions (ADRs) following the use of DNA methylation inhibitors in the World Health Organization (WHO) VigiAccess database and compares the characteristics of ADRs between the two drugs to select the drug with the minimum individualized risk for patients. Methods: This study employed a retrospective descriptive analysis method. We compiled ADR reports for two marketed DNA methylation inhibitors for the treatment of MDS from WHO-VigiAccess. Data collected included demographic data such as age groups, gender, and regions of global patients covered by ADR reports, as well as data on the disease systems and symptoms caused by ADRs recorded in the annual reports and reports received by WHO. By calculating the proportion of ADRs reported for each drug, we compared the similarities and differences in ADRs between the two drugs. Results: Overall, 23,763 adverse events (AEs) related to the two DNA methylation inhibitors were reported in VigiAccess. The results showed that the top 10 most common AEs were febrile neutropenia, bone marrow suppression, neutropenia, anemia, pancytopenia, leukopenia, thrombocytopenia, bone marrow failure, agranulocytosis, and hematotoxicity. The top five common types of DNA methylation inhibitor AEs were blood and lymphatic system disorders (11,178 cases, 47.0%), cardiac organ diseases (1,488 cases, 6.3%), various congenital familial genetic diseases (49 cases, 0.2%), ear and labyrinth diseases (100, 4.2%), and endocrine system diseases (57, 2.4%). Conclusion: There is no Strong correlation between DNA methylation inhibitors and ADRs. Current comparative observational studies of these inhibitors show that there are common and specific adverse reactions in the ADR reports received by WHO for these drugs. Clinicians should improve the rational use of these drugs based on the characteristics of ADRs.

Association of SOGPI in mediating the effect of Phosphatidylcholine on polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, marked by hormonal imbalances and disruptions in glucose and lipid metabolism. Emerging research has indicated a correlation between lipids and PCOS, yet the specific lipid profiles or associated genes identified in various studies vary, and observational data alone cannot establish causation. Therefore, our study seeks to establish a causal association between lipidome and PCOS. METHODS: Data from genome-wide association studies, liposomes, metabolites, and PCOS-related information were collected. Four rounds of double-sample bidirectional intermediate Mendelian Randomization analyses including liposomes to disease, liposomes to metabolites, metabolites to disease, and reverse Mendelian Randomization analysis of lipids, total effect values and intermediary effect values were calculated. The proportion mediated by the intermediary effect was determined by dividing the intermediary effect value by the total effect value. RESULTS: The analyses revealed that three liposomes and nine metabolites were causally associated with PCOS. Specifically, phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol were identified as independent risk factors for PCOS through further Mendelian Randomization analysis. The risk of developing PCOS increased by 32% for every one standard deviation increase in phosphatidylcholine and by 17% for every one standard deviation increase in 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol. Furthermore, the study revealed that phosphatidylcholine can influence the development of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol acting as a mediator, explaining 4.97% of the effect. CONCLUSIONS: This study confirmed a causal relationship between phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol with PCOS, where phosphatidylcholine can influence the occurrence of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol as a mediator.

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics.

There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, and toxicity have been reported in previous studies. Thus there is a dearth of new treatment options for SARS-CoV-2. In this work, a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 activity. One compound, designated 172, demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of concern. Mechanistic studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease (3CLpro) by binding to an allosteric site and reduces 3CLpro dimerization. A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in vitro. In vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 mice. Overall, this study identified an alternative druggable site on the SARS-CoV-2 3CLpro, proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

A novel sequential extraction method for the measurement of Cr(VI) and Cr(III) species distribution in soil: New insights into the chromium speciation.

The distribution characteristics of Cr(VI) species in contaminated soil is crucial for soil remediation; however, there is currently a lack of methods for analysing anionic Cr(VI) species in soil. This study has developed a novel sequential extraction method for speciation of Cr(VI) and Cr(III). Besides extraction experiments, simulated chromium species were prepared to verify the presence of proposed chromium species. The results show that Cr(VI) species in soil can be categorized into water-soluble Cr(VI), electrostatically adsorbed Cr(VI), Cr(VI) specifically adsorbed by minerals containing exchangeable Ca2+, Cr(VI) specifically adsorbed by hydrous metal oxides, calcium chromate Cr(VI) and stable complexed adsorption Cr(VI). These Cr(VI) species can be selectively extracted by specific solutions through ion exchange or weak acid dissolution. The most stable Cr(VI) species is Cr(VI) complexed by hydrous iron oxides through bidentate ligand binding; only by dissolution of hydrous iron oxides can this Cr(VI) species be leached. The distribution of Cr(VI) species is closely linked to particular soil compositions including exchangeable Ca2+ and hydrous iron oxides which determinate the Cr(VI) adsorption in soil. Cr(III) species comprise Fe-Cr coprecipitate hydroxides Cr(III), Fe-Mn oxide-bound Cr(III), organic matter-bound Cr(III) and residual Cr(III). Their distribution depends on the types of reductants present in the soil.

The systemic inflammatory response index is associated with chronic kidney disease in patients with hypertension: data from the national health and nutrition examination study 1999-2018.

BACKGROUND: Studies have shown that in hypertensive patients, chronic kidney disease (CKD) is associated with a poor prognosis. Inflammation is a highly important factor in the progression of CKD. Detecting systemic inflammation and intervening promptly in patients with hypertension may help reduce the risk of CKD. The systemic inflammatory response index (SIRI) is a tool used to measure the systemic inflammatory response, but its relationship with CKD in patients with hypertension remains uncertain. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 1999 and 2018. The analysis included a total of 20,243 participants, categorized into three groups based on SIRI tertiles. Logistic regression analysis and restricted cubic spline analysis were used to examine the relationship between the SIRI and CKD. RESULTS: In patients with hypertension, there was a notable relationship between the SIRI and the odds of developing CKD. After full adjustment, there was a 31% greater likelihood of developing CKD associated with each incremental increase of 1 unit in the SIRI (OR: 1.31, 95% CI: 1.24-1.39, p < 0.001). The groups with greater SIRI values exhibited greater odds of developing CKD than did the T1 group (T2: OR: 1.20, 95% CI: 1.04-1.38, p = 0.015; T3: OR: 1.69, 95% CI: 1.47-1.94, p < 0.001). CONCLUSION: A high SIRI is associated with an increased risk of CKD in hypertensive patients. The greater the SIRI is, the greater the risk of CKD in hypertensive patients.

Construction of a minute ventilation model to address inter-individual inhaled dose variability within identical exposure scenarios using wearable devices.

Inhaled dose is crucial for accurately assessing exposure to air pollution, determined by pollutant concentration and minute ventilation (VE). However, the VE predictive models and its application to assess the health effects of air pollution are still lacking. In this study, we developed VE predictive models using machine learning techniques, utilizing data obtained from eighty participants who underwent a laboratory cardiopulmonary exercise test (CPET). VE predictive models were developed using generalized additive model (GAM), random forest model (RF) and extreme gradient boosting (XGBoost) and analyzed for explanation of input variables. The Random Forest model, cross-validated, exhibited outstanding performance with an R2 of 0.986 and a MAE of 1.816 L/min. The median difference between the measured VE and the predicted VE was 0.18 L/min, and the median difference between the black carbon (BC) inhaled dose based on predicted VE and measured VE was 0.02 ng. Employing explainable machine learning, the results showed that metabolic equivalent (METs), heart rate, and body weight are the three top important variables, emphasizing the significance of incorporating METs variables when constructing VE models. Through multiple linear regression models and an adjusted stratified analysis model, the significant adverse association between BC concentration and inhaled dose on diastolic blood pressure (DBP) was only observed in female. The disparity in the effect of BC inhaled dose compared to BC concentration on DBP reached up to 115 %. This study is the first to explore the ability of different machine learning algorithms to construct VE prediction models and directly apply the models to assess health effects of an example pollutant. This study contributes to the accurate assessment of air pollution exposure leveraging wearable devices, an approach useful for environmental epidemiology studies.

Rational fusion design inspired by cell-penetrating peptide: SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disease induced by multiple interconnected mechanisms. Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology. However, clinical translation of peptide drugs is greatly hampered by their low permeability into brain. Herein, a hybrid peptide HNSS is generated by merging two therapeutic peptides (SS31 and S-14 G Humanin (HNG)), using a different approach from the classical shuttle-therapeutic peptide conjugate design. HNSS demonstrated increased bio-permeability, with a 2-fold improvement in brain distribution over HNG, thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides. HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting, ROS scavenging and p-STAT3 activation. Meanwhile, HNSS with increased Aß affinity greatly inhibited Aß oligomerization/fibrillation, and interrupted Aß interaction with neuron/microglia by reducing neuronal mitochondrial Aß deposition and promoting microglial phagocytosis of Aß. In 3× Tg-AD transgenic mice, HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance. This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification, providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

High-resolution magnetic resonance imaging features of time-of-flight magnetic resonance angiography signal loss and its relevance to ischemic stroke.

Background: Focal signal loss of intracranial artery stenosis is commonly observed on three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA). We aimed to investigate the underlying pathophysiology of vessel signal loss observed on 3D-TOF-MRA and its relevance to recent ischemic stroke. Methods: High-resolution magnetic resonance imaging (HR-MRI) was performed in 401 patients with unilateral or bilateral moderate-to-severe stenosis (50-99%) of the middle cerebral artery (MCA) on TOF-MRA. The patients were classified according to the presence or absence of focal signal loss in the M1 segment of the MCA. The wall features between the vessels with and without signal loss were compared, and their relationship with recent ischemic stroke was analyzed. Results: A total of 414 stenotic lesions caused by atherosclerotic plaque were detected, including 231 with signal loss on TOF-MRA and 183 without. The signal loss group, compared to the group without signal loss, showed a higher degree of stenosis (P<0.001), grade 2 enhanced plaques (82.3% vs. 28.4%; P<0.001), and concentric pattern (63.2% vs. 34.4%; P<0.001). Multivariate analysis suggested grade 2 enhanced plaques and concentric pattern were independently associated with signal loss. Patients in the signal loss group were more likely to have had a recent ischemic stroke (62.4% vs. 40.4%; P<0.001). Conclusions: In addition to the degree of stenosis, the vulnerability and morphology of plaques on HR-MRI may influence signals on 3D-TOF-MRA. The presence of signal loss on 3D-TOF-MRA is associated with recent ischemic stroke.

Optimized terahertz generation in BNA organic crystals with chirped Ti:sapphire laser pulses.

We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

Unraveling the synergistic mechanisms of coagulation combined with oxidation for the treatment of sewer overflow: The interaction between iron species and NaClO.

During wet weather, sewer overflow pollution can pose a serious threat to surface water. In order to reduce the impact of overflow discharge on receiving waters, ferric chloride (Fe(Ⅲ))/potassium ferrate (Fe(Ⅵ))/polyacrylamide (PAM) coagulation (Fe(Ⅲ)/Fe(Ⅵ)/PAM) combined with sodium hypochlorite (NaClO) oxidation was proposed. Different combinations were constructed, including pre-oxidation coagulation (NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM), pre-coagulation oxidation (Fe(Ⅲ)/Fe(Ⅵ)/PAM-NaClO), and synchronous coagulation oxidation (NaClO+Fe(Ⅲ)/Fe(Ⅵ)/PAM). The combined processes achieved efficient removal of conventional contaminants, and the produced byproducts were controlled, especially in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM. The obvious discrepancy in the sulfamethoxazole (SMX) removal was observed in different processes. NaClO affected the distribution of hydrolyzed iron species, and the proportion of active iron in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM significantly increased. More complexation sites were generated in the NaClO-Fe(Ⅲ)/Fe(Ⅵ)/PAM, which can complex with the coagulant and then effectively transfer to the flocs. The composition of the flocs further confirmed the differences in coagulation characteristics. The generated·OH played a crucial role in SMX removal in the NaClO+Fe(Ⅲ)/Fe(Ⅵ)/PAM, and ClO·was responsible for partial removal of ammonia nitrogen (NH4+-N). The contribution of high-valent iron species was confirmed, and the introduction of NaClO promoted the generation of iron species. This study may provide an ideal for overflow treatment to improve the urban water environment.

Social isolation impairs cognition via Aß-mediated synaptic dysfunction.

Social isolation (SI) is a common phenomenon in the modern world, especially during the coronavirus disease 2019 pandemic, and causes lasting cognitive impairments and mental disorders. However, it is still unclear how SI alters molecules in the brain and induces behavioural dysfunctions. Here, we report that SI impairs cognitive function and induces depressive-like behaviours in C57BL/6 J mice, in addition to impairing synaptic plasticity and increasing the levels of APP cleavage-related enzymes, thereby promoting Aß production. Moreover, we show that in APP/PS1 transgenic mice, SI accelerates pathological changes and behavioural deficits. Interestingly, downregulation of the expression of the BACE1 attenuates SI-induced Aß toxicity and synaptic dysfunction. Furthermore, early intervention with BACE1 shRNA blocks SI-induced cognitive impairments. Together, our data strongly suggest that SI-induced upregulation of BACE1 expression mediates Aß toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.

Non-Specific Elevated Serum Free Fatty Acids in Lung Cancer Patients: Nutritional or Pathological?

IMPORTANCE: The reprogramming of lipid metabolism is a significant feature of tumors, yet the circulating levels of fatty acids in lung cancer patients remain to be explored. Moreover, the association between fatty acid levels and related factors, including nutritional intake, tumor metabolism, and tumor immunity, has been rarely discussed. OBJECTIVES: To explore the differences in serum free fatty acids between lung cancer patients and healthy controls, and investigate the factors associated with this phenomenon. DESIGN AND PARTICIPANTS: A case-control study enrolled 430 primary lung cancer patients and 430 healthy controls. The whole population had a medium [Q1, Q3] age of 48.0 [37.0, 58.9] years, with females comprising 56% of the participants. The absolute quantification of 27 serum free fatty acids (FFAs) was measured using a liquid chromatography-mass spectrometry (LC-MS/MS) detection. Data, including dietary intake, blood indicators, and gene expression of lung tissues, were obtained from questionnaires, blood tests, and RNA-sequencing. Statistical differences in FFA levels between lung cancer patients and healthy controls were investigated, and related contributing factors were explored. RESULTS: Levels of 22 FFAs were significantly higher in lung cancer patients compared to those in healthy controls, with fold changes ranging from 1.14 to 1.69. Lung cancer diagnosis models built with clinical and FFA features yielded an area under the receiver operating characteristic curve (AUROC) of 0.830 (0.780-0.880). Total fatty acids (TFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) showed no significant dietary-serum associations, indicating that the elevations might not be attributed to an excessive intake of relevant fatty acids from the diet. For RNA-sequencing of lung tissues, among the 68 lipid metabolism genes, 26 genes showed significant upregulation (FDR < 0.05), while 33 genes exhibited significant downregulation, indicating the involvement of the fatty acids in the tumor metabolism. Through joint analysis with immune cells and inflammatory factors in the blood, fatty acids might exert suppressing effects on tumor immunity. CONCLUSIONS: Lung cancer patients had elevated levels of serum free fatty acids compared to healthy individuals. The elevations might not be attributed to an excessive intake of relevant fatty acids from the diet but related to pathological factors of tumor metabolism and immunity. These findings will complement research on fatty acid metabolism of lung cancer and provide insights into potential intervention targets.

Sensitive colorimetric detection of glutathione in human serum based on peroxidase-like activity of chitosan-stabilized gold nanoparticles.

A colorimetric sensor for the rapid and sensitive detection of GSH was developed. The hydrothermal method was utilized to synthesize chitosan-stabilized gold nanoparticles (CS-AuNPs). The synthesized CS-AuNPs were characterized by UV-vis absorption spectroscopy, transmission electron microscopy (TEM), X-ray diffractograms (XRD), and Fourier transform infrared spectroscopy (FTIR). The CS-AuNPs are well-dispersed and possess a spherical shape with an average particle size of 10.05 ± 2.26 nm in aqueous solution. They show an intrinsic peroxidase-like activity, which could efficiently catalyze the decomposition of H2O2 to produce •OH radicals. These radicals then oxidized 3, 3´, 5, 5´-tetramethylbenzidine (TMB), resulting in the formation of the blue oxidized product oxTMB, observed a visible color change (from colorless to blue), and oxTMB had an obvious absorption peak at 652 nm. The presence of GSH could inhibit the peroxidase-like activity of CS-AuNPs, thereby reducing the formation of oxTMB. The solution's blue hue underwent a reduction in absorption intensity. Based on this fact, a novel and sensitive colorimetric sensor for detection of GSH was constructed. Under optimal conditions, the results of detection had an excellent linear relationship between the concentration of GSH and ∆A within the range 0.5 ~ 50.0 × 10-6 mol/L. The limit of detection (LOD) for GSH was 2.10 × 10-7 mol/L, which was much lower than those in most previous works. Furthermore, for detection in real human serum samples, the recoveries of GSH and the relative standard deviations (RSD) in the serum were in the range 98.40 ~ 103.32% and 1.85 ~ 3.54%, respectively. Thus, this visual colorimetric method has good precision and can be used for GSH detection in practical applications, promising in the fields of bioanalysis and illness diagnostics.

The modulation of temporal predictability on attentional boost effect.

INTRODUCTION: The attentional boost effect, characterized by better memory for background scenes coinciding with a detection target than a nontarget, is believed to stem from a temporary increase in attentional capacity at the time of an acute behavior-related event occurring. Sisk and Jiang's study found that the attentional boost effect also occurs when the target's appearance was predictable. Unfortunately, the duration of the predictive interval in Sisk and Jiang's study was fixed. Since different predictive intervals had different weakening degrees to the acuteness of the target, this fixed duration hindered further investigation into the impact of different levels of predictability on the attentional boost effect. METHOD: Using the encoding-recognition paradigm and the remembering/knowing paradigm, and setting target stimuli with different predictive interval in target detection tasks, the current study aimed to explore the influence of varying the duration of the predictive interval on the attentional boost effect. RESULTS: The attentional boost effect was observed only in the short and medium predictive duration conditions, but not in the long predictive duration condition. Moreover, as the duration of the predictive interval increased, participants' memory performance on target-paired words gradually declined, while their memory performance on distractor-paired and baseline-paired words gradually improved. CONCLUSIONS: Predictability may alter the task demands, allowing participants to more effectively allocate attentional resources to the two tasks at hand.

Exploring the gut microbiome and immunological landscape in kidney cancer: a Mendelian randomization analysis.

Introduction: Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system's contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins. Methods: Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions. Results: Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and ß-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors. Conclusion: Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.

Enhanced desmosome assembly driven by acquired high-level desmoglein-2 promotes phenotypic plasticity and endocrine resistance in ER+ breast cancer.

Acquired resistance to endocrine treatments remains a major clinical challenge. In this study, we found that desmoglein-2 (DSG2) plays a major role in acquired endocrine resistance and cellular plasticity in ER+ breast cancer (BC). By analysing the well-established fulvestrant-resistant ER+ BC model using single-cell RNA-seq, we revealed that ER inhibition leads to a specific increase in DSG2 in cancer cell populations, which in turn enhances desmosome formation in vitro and in vivo and cell phenotypic plasticity that promotes resistance to treatment. DSG2 depletion reduced tumorigenesis and metastasis in fulvestrant-resistant xenograft models and promoted fulvestrant efficiency. Mechanistically, DSG2 forms a desmosome complex with JUP and Vimentin and triggers Wnt/PCP signalling. We showed that elevated DSG2 levels, along with reduced ER levels and an activated Wnt/PCP pathway, predicted poor survival, suggesting that a DSG2high signature could be exploited for therapeutic interventions. Our analysis highlighted the critical role of DSG2-mediated desmosomal junctions following antiestrogen treatment.