Correlation of SARS-CoV-2 in Wastewater and Individual Testing Results in a Jail, Atlanta, Georgia, USA.

Institution-level wastewater-based surveillance was implemented during the COVID-19 pandemic, including in carceral facilities. We examined the relationship between COVID-19 diagnostic test results of residents in a jail in Atlanta, Georgia, USA (average population ≈2,700), and quantitative reverse transcription PCR signal for SARS-CoV-2 in weekly wastewater samples collected during October 2021‒May 2022. The jail offered residents rapid antigen testing at entry and periodic mass screenings by reverse transcription PCR of self-collected nasal swab specimens. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between strength of SARS-CoV-2 PCR signal (cycle threshold value) in wastewater and percentage of jail population that tested positive for COVID-19. Of 13,745 nasal specimens collected, 3.9% were COVID-positive (range 0%-29.5% per week). We observed a strong inverse correlation between diagnostic test positivity and cycle threshold value (r = -0.67; p<0.01). Wastewater-based surveillance represents an effective strategy for jailwide surveillance of COVID-19.

Toward High-Energy-Density Initial-Anode-Free Lithium-Metal Batteries via Ultra-Thin Protective Ion-Transport-Promoting Interface Modification and Surface Prelithiation.

Anode-free lithium-metal batteries (AFLMBs) are desirable candidates for achieving high-energy-density batteries, while severe active Li+ loss and uneven Li plating/stripping behavior impede their practical application. Herein, a trilaminar LS-Cu (LiCPON + Si/C-Cu) current collector is fabricated by radio frequency magnetron sputtering, including a Si/C hybrid lithiophilic layer and a supernatant carbon-incorporated lithium phosphorus oxynitride (LiCPON) solid-state electrolyte layer. Joint experimental and computational characterizations and simulations reveal that the LiCPON solid-state electrolyte layer can decompose into an in situ stout ion-transport-promoting protective layer, which can not only regulate homogeneous Li plating/stripping behavior but also inhibit the pulverization and deactivation of Si/C hybrid lithiophilic layer. When combined with surface prelithiated Li1.2Ni0.13Co0.13Mn0.54O2 (Preli-LRM) cathode, the Preli-LRM||LS-Cu full cell delivers 896.1 Wh kg-1 initially and retains 354.1 Wh kg-1 after 50 cycles. This strategy offers an innovative design of compensating for active Li+ loss and inducing uniform Li plating/stripping behavior simultaneously for the development of AFLMBs.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity.

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Causal associations between sleep traits and brain structure: a bidirectional Mendelian randomization study.

BACKGROUND: Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders. RESULTS: After Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (ß, 0.26; 95% CI, 0.15-0.37; P = 5.27 × 10-6). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85-0.94; P = 1.51 × 10-5) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97-0.99; P = 1.51 × 10-5), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (ß, - 0.09; 95%CI, - 0.13 to - 0.05; P = 1.21 × 10-5). CONCLUSIONS: Sleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.

Estimating seroconversion rates accounting for repeated infections by approximate Bayesian computation.

This study presents a novel approach for inferring the incidence of infections by employing a quantitative model of the serum antibody response. Current methodologies often overlook the cumulative effect of an individual's infection history, making it challenging to obtain a marginal distribution for antibody concentrations. Our proposed approach leverages approximate Bayesian computation to simulate cross-sectional antibody responses and compare these to observed data, factoring in the impact of repeated infections. We then assess the empirical distribution functions of the simulated and observed antibody data utilizing Kolmogorov deviance, thereby incorporating a goodness-of-fit check. This new method not only matches the computational efficiency of preceding likelihood-based analyses but also facilitates the joint estimation of antibody noise parameters. The results affirm that the predictions generated by our within-host model closely align with the observed distributions from cross-sectional samples of a well-characterized population. Our findings mirror those of likelihood-based methodologies in scenarios of low infection pressure, such as the transmission of pertussis in Europe. However, our simulations reveal that in settings of higher infection pressure, likelihood-based approaches tend to underestimate the force of infection. Thus, our novel methodology presents significant advancements in estimating infection incidence, thereby enhancing our understanding of disease dynamics in the field of epidemiology.

Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum.

BACKGROUND: Genogroup II noroviruses are the most common cause of acute infectious gastroenteritis. We evaluated the use of a new GII.2 inoculum in a human challenge. METHODS: Forty-four healthy adults (36 secretor-positive and 8 secretor-negative for histo-blood group antigens) were challenged with ascending doses of a new safety-tested Snow Mountain virus (SMV) GII.2 norovirus inoculum (1.2 × 104 to 1.2 × 107 genome equivalent copies [GEC]; n = 38) or placebo (n = 6). Illness was defined as diarrhea and/or vomiting postchallenge in subjects with evidence of infection (defined as GII.2 norovirus RNA detection in stool and/or anti-SMV immunoglobulin G [IgG] seroconversion). RESULTS: The highest dose was associated with SMV infection in 90%, and illness in 70% of subjects with 10 of 12 secretor-positive (83%) and 4 of 8 secretor-negative (50%) becoming ill. There was no association between prechallenge anti-SMV serum IgG concentration, carbohydrate-binding blockade antibody, or salivary immunoglobulin A and infection. The median infectious dose (ID50) was 5.1 × 105 GEC. CONCLUSIONS: High rates of infection and illness were observed in both secretor-positive and secretor-negative subjects in this challenge study. However, a high dose will be required to achieve the target of 75% illness to make this an efficient model for evaluating potential norovirus vaccines and therapeutics. CLINICAL TRIALS REGISTRATION: NCT02473224.

The Role of Staff in Transmission of SARS-CoV-2 in Long-term Care Facilities.

BACKGROUND: US long-term care facilities (LTCFs) have experienced a disproportionate burden of COVID-19 morbidity and mortality. METHODS: We examined SARS-CoV-2 transmission among residents and staff in 60 LTCFs in Fulton County, Georgia, from March 2020 to September 2021. Using the Wallinga-Teunis method to estimate the time-varying reproduction number, R(t), and linear-mixed regression models, we examined associations between case characteristics and R(t). RESULTS: Case counts, outbreak size and duration, and R(t) declined rapidly and remained low after vaccines were first distributed to LTCFs in December 2020, despite increases in community incidence in summer 2021. Staff cases were more infectious than resident cases (average individual reproduction number, R i = 0.6 [95% confidence intervals [CI] = 0.4, 0.7] and 0.1 [95% CI = 0.1, 0.2], respectively). Unvaccinated resident cases were more infectious than vaccinated resident cases (R i = 0.5 [95% CI = 0.4, 0.6] and 0.2 [95% CI = 0.0, 0.8], respectively), but estimates were imprecise. CONCLUSIONS: COVID-19 vaccines slowed transmission and contributed to reduced caseload in LTCFs. However, due to data limitations, we were unable to determine whether breakthrough vaccinated cases were less infectious than unvaccinated cases. Staff cases were six times more infectious than resident cases, consistent with the hypothesis that staff were the primary drivers of SARS-CoV-2 transmission in LTCFs.

Anomalous Redox Features Induced by Strong Covalency in Layered NaTi1-y Vy S2 Cathodes for Na-Ion Batteries.

The rising demand for energy density of cathodes means the need to raise the voltage or capacity of cathodes. Transition metal (TM) doping has been employed to enhance the electrochemical properties in multiple aspects. The redox voltage of doped cathodes usually falls in between the voltage of undoped layered cathodes. However, we found anomalous redox features in NaTi1-y Vy S2 . The first discharge platform potential (2.4 V) is significantly higher than that of undoped NaTiS2 and NaVS2 (both around 2.2 V), and the energy density is raised by 15 %. We speculate that the anomalous voltage is mainly attributed to the strong hybridization in the Ti-V-S system. Ti3+ and V3+ undergo charge transfer and form a more stable Ti (t2g 0 eg 0 ) and V (t2g 3 eg 0 ) electronic configuration. Our results indicate that higher voltage of cathode materials could be achieved by strong TM-ligand covalency, and this conclusion provides possible opportunities to explore high voltage materials for future layered cathodes.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Georgia, USA, February 1-July 13, 2020.

The serial interval and effective reproduction number for coronavirus disease (COVID-19) are heterogenous, varying by demographic characteristics, region, and period. During February 1-July 13, 2020, we identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. We examined how various transmission characteristics were affected by symptoms, demographics, and period (during shelter-in-place and after subsequent reopening) and estimated the time course of reproduction numbers for all 159 Georgia counties. Transmission varied by time and place but also by persons' sex and race. The mean serial interval decreased from 5.97 days in February-April to 4.40 days in June-July. Younger adults (20-50 years of age) were involved in most transmission events occurring during or after reopening. The shelter-in-place period was not long enough to prevent sustained virus transmission in densely populated urban areas connected by major transportation links.

Factors associated with health facility deliveries among mothers living in hospital catchment areas in Rukungiri and Kanungu districts, Uganda.

BACKGROUND: Health facility deliveries are generally associated with improved maternal and child health outcomes. However, in Uganda, little is known about factors that influence use of health facilities for delivery especially in rural areas. In this study, we assessed the factors associated with health facility deliveries among mothers living within the catchment areas of major health facilities in Rukungiri and Kanungu districts, Uganda. METHODS: Cross-sectional data were collected from 894 randomly-sampled mothers within the catchment of two private hospitals in Rukungiri and Kanungu districts. Data were collected on the place of delivery for the most recent child, mothers' sociodemographic and economic characteristics, and health facility water, sanitation and hygiene (WASH) status. Modified Poisson regression was used to estimate prevalence ratios (PRs) for the determinants of health facility deliveries as well as factors associated with private versus public utilization of health facilities for childbirth. RESULTS: The majority of mothers (90.2%, 806/894) delivered in health facilities. Non-facility deliveries were attributed to faster progression of labour (77.3%, 68/88), lack of transport (31.8%, 28/88), and high cost of hospital delivery (12.5%, 11/88). Being a business-woman [APR = 1.06, 95% CI (1.01-1.11)] and belonging to the highest wealth quintile [APR = 1.09, 95% CI (1.02-1.17)] favoured facility delivery while a higher parity of 3-4 [APR = 0.93, 95% CI (0.88-0.99)] was inversely associated with health facility delivery as compared to parity of 1-2. Factors associated with delivery in a private facility compared to a public facility included availability of highly skilled health workers [APR = 1.15, 95% CI (1.05-1.26)], perceived higher quality of WASH services [APR = 1.11, 95% CI (1.04-1.17)], cost of the delivery [APR = 0.85, 95% CI (0.78-0.92)], and availability of caesarean services [APR = 1.13, 95% CI (1.08-1.19)]. CONCLUSION: Health facility delivery service utilization was high, and associated with engaging in business, belonging to wealthiest quintile and having higher parity. Factors associated with delivery in private facilities included health facility WASH status, cost of services, and availability of skilled workforce and caesarean services.

Assessment of water, sanitation and hygiene service availability in healthcare facilities in the greater Kampala metropolitan area, Uganda.

BACKGROUND: Improved Water, Sanitation and Hygiene (WASH) in Healthcare facilities (HCFs) is of significant public health importance. It is associated with a reduction in the transmission of healthcare acquired infections (HAIs), increased trust and uptake of healthcare services, cost saving from infections averted, increased efficiency and improved staff morale. Despite these benefits, there is limited evidence on availability of WASH services in HCFs in the Greater Kampala Metropolitan Area (GKMA). This study assessed the availability and status of WASH services within HCFs in the GKMA in order to inform policy and WASH programming. METHODS: A cross-sectional study was conducted in 60 HCFs. Availability of WASH services in the study HCFs was assessed using a validated WASH Conditions (WASHCon) tool comprising of structured interviews, HCF observations and microbial water quality analysis. Data were analysed using Stata 14 software and R software. RESULTS: Overall, 84.5% (49/58) and 12.1% (7/58) of HCFs had limited and basic WASH service respectively. About 48.3% (28/58) had limited water service, 84.5% (49/58) had limited sanitation service, 50.0% (29/58) had limited environmental cleanliness service, 56.9% (33/58) had limited hand hygiene service, and 51.7% (30/58) had limited waste management service. About 94.4% of public HCFs had limited WASH service compared to only 68.2% of private not for profit facilities. More health centre IIIs, 92.5% and health centre IVs (85.7%) had limited WASH service compared to hospitals (54.5%). CONCLUSIONS: Our findings indicate that provision of water, sanitation, hand hygiene, environmental cleanliness, and health care waste management services within HCFs is largely hindered by structural and performance limitations. In spite of these limitations, it is evident that environmental cleanliness and treatment of infectious waste can be attained with better oversight and dedicated personnel. Attaining universal WASH coverage in HCFs will require deliberate and strategic investments across the different domains.

Construction of an Electrochemical Receptor Sensor Based on Graphene/Thionine for the Sensitive Determination of ß-Lactam Antibiotics Content in Milk.

In antibiotics, ß-lactam is one kind of major concern acknowledged as an unavoidable contaminant in milk. Thus, a facile and sensitive method is essential for rapid ß-lactam antibiotics detection. In our work, a specific electrochemical receptor sensor based on the graphene/thionine (GO/TH) composite was established. The mechanism of the electrochemical receptor sensor was a direct competitive inhibition of the binding of horseradish peroxidase-labeled ampicillin (HRP-AMP) to the mutant BlaR-CTD protein by free ß-lactam antibiotics. Then, horseradish peroxidase (HRP) catalyzed the hydrolysis of the substrate hydrogen peroxide (H2O2), which produced an electrochemical signal. Under optimal experimental conditions, this method could quantitatively detect cefquinome from 0.1 to 8 µg L-1 and with the limit of detection (LOD) of 0.16 µg L-1, much lower than the maximum residue limit (MRL) of 5 µg L-1 set by the European Union. In addition, the LOD of spiked milk samples with cefalexin, cefquinoxime, cefotafur, penicillin G and ampicillin were 14.88 µg L-1, 2.46 µg L-1, 17.16 µg L-1, 0.06 µg L-1, 0.21 µg L-1 and the limits of quantitation (LOQ) were 36.09 µg L-1, 5.40 µg L-1, 41.45 µg L-1, 0.13 µg L-1, 0.42 µg L-1, respectively. The sensor showed a favorable recovery of 84.89-102.44%. Moreover, the electrochemical receptor sensor was successfully applied to assay ß-lactam antibiotics in milk, which showed good correlation with the results obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Children Are Exposed to Fecal Contamination via Multiple Interconnected Pathways: A Network Model for Exposure Assessment.

In recent decades, quantitative microbial risk assessment (QMRA) has been widely used to assess exposure to fecal microbes and associated health risks. In this study, a multipathway exposure assessment model was developed to evaluate exposure to fecal microbes for children under 5 in highly contaminated urban environments. Children had contact with various environmental compartments. The contamination levels of these compartments were estimated from fecal indicator counts in the environmental samples. Structured observations of child behavior (including activities, locations, and time) were used to model behavioral sequences as a dynamic network. The exposure model combines behavior sequences with environmental contamination, using additional exposure factors when needed, to estimate the number of fecal microbes transferred from environmental sources to human oral ingestion. As fecal exposure in a highly contaminated urban environment consists of contributions from multiple pathways, it is imperative to study their relative importance. The model helps us better understand the characteristics of the exposure pathways that may be driven by variation in contamination and by variable behavior, like hygiene and high-risk activities. Importantly, the model also allows prediction of the quantitative effects of an intervention-the expected reduction in exposure due to infrastructural or behavioral changes-by means of scenario studies. Based on experience with this exposure model, we make specific recommendations for additional studies of child behavior and exposure factors in order to fill critical information gaps and improve the model structure and assumptions.

Diagnostic accuracy of low-dose 256-slice multi-detector coronary CT angiography using iterative reconstruction in patients with suspected coronary artery disease.

OBJECTIVES: To evaluate the accuracy of low-dose coronary CTA with iterative reconstruction (IR) in the diagnosis of coronary artery disease (CAD) in patients with suspected CAD. METHODS: Ninety-six patients with suspected CAD underwent low-dose prospective electrocardiogram-gated coronary CTA, with images reconstructed using IR. Image quality (IQ) of coronary segments were graded on a 4-point scale (4, excellent; 1, non-diagnostic). With invasive coronary angiography (ICA) considered the "gold standard", the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of coronary CTA were calculated on segment-, vessel- and patient-based levels. The patient data were divided into two groups (Agatston scores of ≥ 400 and <400). The differences in diagnostic performance between the two groups were tested. RESULTS: Diagnostic image quality was found in 98.1 % (1,232/1,256) of segments. The sensitivity, specificity, PPV, NPV and accuracy were 90.8 %, 95.3 %, 81.8 %, 97.8 % and 94.3 % (segment-based) and 97.2 %, 83.3 %, 94.6 %, 90.9 % and 93.8 % (patient-based). Significant differences between the two groups were seen in specificity, PPV and accuracy (92.1 % vs. 97.9 %, 76.0 % vs. 86.7 %, 91.7 % vs. 96.6 %, P < 0.05; segment-based). The average effective dose was 1.30 ± 0.15 mSv. CONCLUSION: Low-dose prospective coronary CTA with IR can acquire satisfactory image quality and show high diagnostic accuracy in patients with suspected CAD; however, blooming continues to pose a challenge in severely calcified segments. KEY POINTS: • Coronary artery disease (CAD) is increasingly investigated using coronary CTA. • The iterative reconstruction (IR) algorithm is promising in decreasing radiation doses. • Low-dose prospective coronary CTA with IR can acquire satisfactory image quality. • Low-dose prospective coronary CTA with IR can show high diagnostic accuracy.

Targeting CD8+ T cells with natural products for tumor therapy: Revealing insights into the mechanisms.

BACKGROUND: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential. Notably, emerging evidences have suggested that several natural compounds may boost the anti-tumor effects through activating immune response of hosts, in which CD8+ T cells play a pivotal role. METHODS: The data of this review come from PubMed, Web of Science, Google Scholar, and ClinicalTrials (https://clinicaltrials.gov/) with the keywords "CD8+ T cell", "anti-tumor", "immunity", "signal 1", "signal 2", "signal 3", "natural products", "T cell receptor (TCR)", "co-stimulation", "co-inhibition", "immune checkpoint", "inflammatory cytokine", "hesperidin", "ginsenoside", "quercetin", "curcumin", "apigenin", "dendrobium officinale polysaccharides (DOPS)", "luteolin", "shikonin", "licochalcone A", "erianin", "resveratrol", "procyanidin", "berberine", "usnic acid", "naringenin", "6-gingerol", "ganoderma lucidum polysaccharide (GL-PS)", "neem leaf glycoprotein (NLGP)", "paclitaxel", "source", "pharmacological activities", and "toxicity". These literatures were published between 1993 and 2023. RESULTS: Natural products have considerable advantages as anti-tumor drugs based on the various species, wide distribution, low price, and few side effects. This review summarized the effects and mechanisms of some natural products that exhibit anti-tumor effects via targeting CD8+ T cells, mainly focused on the three signals that activate CD8+ T cells: TCR, co-stimulation, and inflammatory cytokines. CONCLUSION: Clarifying the role and underlying mechanism of natural products in cancer immunotherapy may provide more options for combinational treatment strategies and benefit cancer therapy, to shed light on identifying potential natural compounds for improving the clinical outcome in cancer immunotherapy.

Characterization of three non-canonical N-glycosylation motifs indicates Nglyco-A reduces DNA N6-methyladenine and Nglyco-D alters G/F actin ratio in Phytophthora sojae.

Asparagine (Asn, N)-linked glycosylation is an abundant post-translational modification in which Asn, typically in Nglyco-X-S/T; X ≠ P motifs, are modified with N-glycans. It has essential regulatory roles in multicellular organisms. In this study, we systematically investigate the function of three N-glycosylation motifs (Nglyco-A, Nglyco-D and Nglyco-S) previously identified in Phytophthora sojae, through site-directed mutagenesis and functional assays. In P. sojae expressing glycosylation-dead variants pre-PsDMAP1N70A (Nglyco-A motif) or PsADFN64A (Nglyco-D motif), zoospore release or cyst germination is impaired. In particular, the pre-PsDMAP1N70A mutant reduces DNA methylation levels, and the PsADFN64A mutant disrupts the actin forms, which could explain the decrease in pathogenicity after N-glycosylation is destroyed. Similarly, P. sojae expressing PsNRXN132A (Nglyco-S motif) shows increased sensitivity to H2O2 and heat. Through autophagy or 26S proteasome pathway inhibition assays, we found that unglycosylated pre-PsDMAP1N70A and PsADFN64A are degraded via the 26S proteasome pathway, while the autophagy pathway is responsible for PsNRXN132A clearance. These findings demonstrate that glycosylation of these motifs regulates the stability and function of glycoproteins necessary for P. sojae growth, reproduction and pathogenicity, which expands the scope of known N-glycosylation regulatory functions in oomycetes.

High Young's Modulus LixTiO2 Layer Suppressing the Pulverization and Deactivation of Lithiophilic Ag Nanoparticles.

Anode-free Lithium metal batteries, with their high energy density (>500 Wh/kg), are emerging as a promising solution for high-energy-density rechargeable batteries. However, the Coulombic Efficiency and capacity often decline due to interface side reactions. To address this, a lithiophilic layer is introduced, promoting stable and uniform Li deposition. Despite its effectiveness, this layer often undergoes electrochemical deactivation over time. This work investigates lithiophilic silver (Ag), prepared via magnetron sputtering on a copper (Cu) current collector. Finite element simulations identify stress changes from alloying reactions as a key cause of Ag particle pulverization and deactivation. A high Young's modulus coating layer is proposed to mitigate this. The Ag2TiO3@Ag@TiO2@Cu composite electrode, designed with multi-layer structures, demonstrates a slower deactivation process through galvanostatic electrochemical cycling. Characterization methods such as SEM, AFM, and TEM confirm the suppression of Ag particle pulverization, while uncoated Ag fractures and deactivates. This work uncovers a potential failure mechanism of lithiophilic metallic nanoparticles and proposes a strategy for deactivation suppression using an artificial coating layer.

Acute toxicology on Danio rerio embryo and adult from Chinese traditional medicine preparation Danggui Shaoyao san.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100 mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200 mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100 mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100 mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100 mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.

Targeting Metabolic-Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy.

Drug resistance is currently one of the biggest challenges in cancer treatment. With the deepening understanding of drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations of redox balance. Notably, metabolic reprogramming mediates the survival of tumor cells in harsh environments, thereby promoting the development of drug resistance. In addition, the changes during metabolic pattern shift trigger reactive oxygen species (ROS) production, which in turn regulates cellular metabolism, DNA repair, cell death, and drug metabolism in direct or indirect ways to influence the sensitivity of tumors to therapies. Therefore, the intersection of metabolism and ROS profoundly affects tumor drug resistance, and clarifying the entangled mechanisms may be beneficial for developing drugs and treatment methods to thwart drug resistance. In this review, we will summarize the regulatory mechanism of redox and metabolism on tumor drug resistance and highlight recent therapeutic strategies targeting metabolic-redox circuits, including dietary interventions, novel chemosynthetic drugs, drug combination regimens, and novel drug delivery systems.

Semi-automated protocol to quantify and characterize fluorescent three-dimensional vascular images.

The microvasculature facilitates gas exchange, provides nutrients to cells, and regulates blood flow in response to stimuli. Vascular abnormalities are an indicator of pathology for various conditions, such as compromised vessel integrity in small vessel disease and angiogenesis in tumors. Traditional immunohistochemistry enables the visualization of tissue cross-sections containing exogenously labeled vasculature. Although this approach can be utilized to quantify vascular changes within small fields of view, it is not a practical way to study the vasculature on the scale of whole organs. Three-dimensional (3D) imaging presents a more appropriate method to visualize the vascular architecture in tissue. Here we describe the complete protocol that we use to characterize the vasculature of different organs in mice encompassing the methods to fluorescently label vessels, optically clear tissue, collect 3D vascular images, and quantify these vascular images with a semi-automated approach. To validate the automated segmentation of vascular images, one user manually segmented one hundred random regions of interest across different vascular images. The automated segmentation results had an average sensitivity of 83±11% and an average specificity of 91±6% when compared to manual segmentation. Applying this procedure of image analysis presents a method to reliably quantify and characterize vascular networks in a timely fashion. This procedure is also applicable to other methods of tissue clearing and vascular labels that generate 3D images of microvasculature.