Electrodeposited Poly(5-Amino-2-Naphthalenesulfonic Acid-co-o-Aminophenol) as the Electrode Material for Flexible Supercapacitor.

Copolymers of 5-amino-2-naphthalenesulfonic acid (ANS) and o-aminophenol (oAP) are electropolymerized on carbon cloth substrate from aqueous solutions, and the electropolymerization process is investigated using electrochemical quartz-crystal microbalance. The surface of the copolymer (PANS-co-oAP) appears rough and is capable to store charge as the battery-type electrode in 1 m H2 SO4 (102.9 mAh g-1 at 1 A g-1 ) or in 1 m ZnSO4 (79.75 mAh g-1 at 1 A g-1 ) aqueous solutions. Compared with PANS and PoAP, the high specific capacity of the PANS-co-oAP is originated from the increased number of electrochemically active sites and increased diffusion rates of ions. Evidence of amino/imino and hydroxyl/carbonyl groups redox processes and cation insertion and extraction are given by ex situ X-ray photoelectron spectroscopy. When used as the electrode material in the flexible solid-state supercapacitors, the specific capacitance is at 37.9 F g-1 which does not significantly alter with the bending angle. The flexible solid-state supercapacitor shows a specific energy of 5.4 Wh kg-1 and a power density of 250.3 W kg-1 at 0.5 A g-1 , and a high capacitance retention (88.2%) after 3000 cycles at 5 A g-1 is achieved.

Precise Design and Modification Engineering of Single-Atom Catalytic Materials for Oxygen Reduction.

Due to their unique electronic and structural properties, single-atom catalytic materials (SACMs) hold great promise for the oxygen reduction reaction (ORR). Coordinating environmental and engineering strategies is the key to improving the ORR performance of SACMs. This review summarizes the latest research progress and breakthroughs of SACMs in the field of ORR catalysis. First, the research progress on the catalytic mechanism of SACMs acting on ORR is reviewed, including the latest research results on the origin of SACMs activity and the analysis of pre-adsorption mechanism. The study of the pre-adsorption mechanism is an important breakthrough direction to explore the origin of the high activity of SACMs and the practical and theoretical understanding of the catalytic process. Precise coordination environment modification, including in-plane, axial, and adjacent site modifications, can enhance the intrinsic catalytic activity of SACMs and promote the ORR process. Additionally, several engineering strategies are discussed, including multiple SACMs, high loading, and atomic site confinement. Multiple SACMs synergistically enhance catalytic activity and selectivity, while high loading can provide more active sites for catalytic reactions. Overall, this review provides important insights into the design of advanced catalysts for ORR.

Study on Tin-Cobalt Bimetallic Phosphide Nanoparticles as a Negative Electrode of Sodium-Ion Batteries.

Tin phosphide (Sn4P3) holds great promise because sodium-ion batteries use this material as an anode with impressive theoretical capacity. In this paper, it is reported that Co-doped Sn4P3 is embedded into carbon-based materials and SnCoP/C with a porous skeleton is prepared. As a result, SnCoP/C-2, as the material utilized in sodium-ion battery anodes, exhibits reversible capacities at 415.6, 345.9, and 315.6 mAh g-1 at current intensities of 0.5, 1.0, and 2.0 A g-1, respectively. The electrochemical reversibility, cycle stability, and rate performance of SnCoP/C samples are obviously better than those of Sn4P3/C. Cobalt in SnCoP/C stabilizes the conductive matrix of tin phosphide and promotes the diffusion kinetics of sodium. These results show that, with an appropriate amount of cobalt doping, highly dispersed nanoparticles can be formed in the tin phosphide matrix, which can significantly enhance the cycle stability of tin-based electrode materials.

Pregnancy health in a multi-state U.S. population of systemically underserved patients and their children: PROMISE cohort design and baseline characteristics.

BACKGROUND: Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. METHODS: We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005-2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. RESULTS: The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. CONCLUSIONS: The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

EVALUATION OF PLASMA CORTISOL AND LACTATE IN KOI (CYPRINUS CARPIO) EUTHANIZED BY IMMERSION IN TRICAINE METHANESULFONATE, CLOVE OIL, OR CARBON DIOXIDE GAS DISSOLVED IN WATER.

Little research has taken place on the effect of euthanasia methods on biophysical and biochemical changes at the time of euthanasia in fish. These changes are used in multiple species to determine stress levels before death. Koi (Cyprinus carpio) are an important fish species often used in laboratory research, kept in backyard ponds, and managed in zoological and aquarium collections. The current study evaluated euthanasia of koi by immersion in 0.5 g/L tricaine methanesulfonate (MS-222) (n = 10), 0.5 g/L clove oil (n = 8), 1 g/L clove oil (n = 10), and CO2 (n = 7) on time to cessation of opercular movement, plasma lactate levels, and plasma cortisol levels. CO2 had the longest mean time to cessation of opercular movement, and MS-222 had the shortest (mean CO2: 24.9 min, range 13.18-31.35 min; MS-222: 2.68 min, range 1.33-4.5 min). The difference was not significant between any of the groups for plasma cortisol or lactate levels. MS-222 demonstrated the highest cortisol levels, and CO2 had the lowest (mean CO2: 108.7 ng/ml, range 33.9-195.8 ng/ml; MS-222: 650.6 ng/ml, range 77.3-2374.9 ng/ml). Average lactate levels were highest for 1 g/L clove oil and lowest for 0.5 g/L clove oil (mean 0.5 g/L clove oil: 5.1 mmol/L, range 1.8-8.1 mmol/L; 1 g/L clove oil: 7.4 mmol/L, range 5.6-10.5 mmol/L).

[Experimental study on improvement of cognitive impairment in Alzheimer's disease by different degrees of steaming and sunning of Polygoni Multiflori Radix based on fecal metabolomics].

The fecal metabolomics method was employed to investigate the cognitive improvement mechanism of Polygoni Multiflori Radix in Alzheimer's disease(AD) and examine the effects of different degrees of steaming and sunning on cognitive function in AD model mice. Additionally, the processing principle of Polygoni Multiflori Radix was discussed. Forty-eight 5-month-old APP/PS1 mice were randomly assigned to the following groups: model group, positive group, raw product group, three-steaming and three-sunning product group, six-steaming and six-sunning product group, and nine-steaming and nine-sunning product group. Seven negative control mice from the same litter were included as the blank group. After 150 days of intragastric administration, the learning and memory abilities of mice in each group were assessed by using the Barnes maze and dark avoidance tests. Fecal samples were collected for extensive targeted metabolomics testing. Principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and other multivariate statistical methods were utilized to analyze metabolites in mouse feces. Comparison of behavioral results between the model group and different product groups demonstrated that the six-steaming and six-sunning product group exhibited significantly reduced latency in the Barnes maze positioning and navigation test(P<0.05), as well as a notable decrease in the number of errors in the space exploration experiment(P<0.05). Moreover, the latency of mice entering the dark box for the first time in the dark avoidance experiment was significantly prolonged(P<0.05), indicating the best overall improvement in the learning and memory ability of AD model mice. Metabolomics results revealed that compared with the model group, the differential metabolites in other groups in descending order were as follows: six-steaming and six-sunning product group > nine-steaming and nine-sunning product group > raw product group > three-steaming and three-sunning product group, encompassing 146, 120, 95, and 81 potential biomarkers, respectively. Among them, 16 differential metabolites were related to AD disease. Further comparisons based on the degree of processing indicated that the six-steaming and six-sunning product group exhibited the most significant adjustments in total metabolic pathways, particularly regulating the interconversion of pentose and glucuronic acid, as well as amino acid anabolism and other pathways. In summary, the mechanism of Polygoni Multiflori Radix after processing in enhancing the learning and memory ability of APP/PS1 mice may be associated with improved amino acid metabolism and increased energy metabolism in the body. The six-steaming and six-sunning yielded the best outcomes.

Fe, N-Inducing Interfacial Electron Redistribution in NiCo Spinel on Biomass-Derived Carbon for Bi-functional Oxygen Conversion.

Herein, an interfacial electron redistribution is proposed to boost the activity of carbon-supported spinel NiCo2O4 catalyst toward oxygen conversion via Fe, N-doping strategy. Fe-doping into octahedron induces a redistribution of electrons between Co and Ni atoms on NiCo1.8Fe0.2O4@N-carbon. The increased electron density of Co promotes the coordination of water to Co sites and further dissociation. The generation of proton from water improves the overall activity for the oxygen reduction reaction (ORR). The increased electron density of Ni facilitates the generation of oxygen vacancies. The Ni-VO-Fe structure accelerates the deprotonation of *OOH to improve the activity toward oxygen evolution reaction (OER). N-doping modulates the electron density of carbon to form active sites for the adsorption and protonation of oxygen species. Fir wood-derived carbon endows catalyst with an integral structure to enable outstanding electrocatalytic performance. The NiCo1.8Fe0.2O4@N-carbon express high half-wave potential up to 0.86 V in ORR and low overpotential of 270 mV at 10 mA cm-2 in OER. The zinc-air batteries (ZABs) assembled with the as-prepared catalyst achieve long-term cycle stability (over 2000 cycles) with peak power density (180 mWcm-2). Fe, N-doping strategy drives the catalysis of biomass-derived carbon-based catalysts to the highest level for the oxygen conversion in ZABs.

Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.

Heterogeneous Catalysis in Production and Utilization of Formic Acid for Renewable Energy.

As the cleanest energy source, hydrogen has been followed with interest by researchers around the world. However, due to the internal low density of hydrogen, it cannot be stored and used efficiently which limits the hydrogen application on a huge scale. Chemical hydrogen storage is considered as a useful method for efficient handling and storage. Due to its excellent safety, formic acid stands out. It is worth noting that the matter and energy conversion is established based on formic acid, which is not referred to in the previous documentation. In this review, the latest development of research on heterogeneous catalysis via production and application of formic acid for energy application is reported. The matter and energy conversion based on formic acid are both discussed systematically. More importantly, with formic acid as the node, biomass energy shows potential to be in a dominant position in the energy conversion process. In addition, the catalytic mechanism is also mentioned. This review can provide the current state in this field and the new inspirations for developing superior catalytic systems.

Co-Adjusting d-Band Center of Fe to Accelerate Proton Coupling for Efficient Oxygen Electrocatalysis.

The problem in d-band center modulation of transition metal-based catalysts for the rate-determining steps of oxygen conversion is an obstacle to boost the electrocatalytic activity by accelerating proton coupling. Herein, the Co doping to FeP is adopted to modify the d-band center of Fe. Optimized Fe sites accelerate the proton coupling of oxygen reduction reaction (ORR) on N-doped wood-derived carbon through promoting water dissociation. In situ generated Fe sites optimize the adsorption of oxygen-related intermediates of oxygen evolution reaction (OER) on CoFeP NPs. Superior catalytic activity toward ORR (half-wave potential of 0.88 V) and OER (overpotential of 300 mV at 10 mA cm-2 ) express an unprecedented level in carbon-based transition metal-phosphide catalysts. The liquid zinc-air battery presents an outstanding cycling stability of 800 h (2400 cycles). This research offers a newfangled perception on designing highly efficient carbon-based bifunctional catalysts for ORR and OER.

Latino Adolescent-Mother Language Concordance, Neighborhood Deprivation, and Vaccinations in Community Health Centers.

INTRODUCTION: Latino adolescents may face numerous barriers) to recommended vaccinations. There is little research on the association between Latino adolescent-mother preferred language concordance and vaccination completion and if it varies by neighborhood. To better understand the social/family factors associated with Latino adolescent vaccination, we studied the association of adolescent-mother language concordance and neighborhood social deprivation with adolescent vaccination completion. METHODS: We employed a multistate, electronic health record (EHR) based dataset of community health center patients to compare three Latino groups: (1) English-preferring adolescents with English-preferring mothers, (2) Spanish-preferring adolescents with Spanish-preferring mothers, and (3) English-preferring adolescents with Spanish-preferring mothers with non-Hispanic white adolescent-mother pairs for human papilloma virus (HPV), meningococcal, and influenza vaccinations. We adjusted for mother and adolescent demographics and care utilization and stratified by the social deprivation of the family's neighborhood. RESULTS: Our sample included 56,542 adolescent-mother dyads. Compared with non-Hispanic white dyads, all three groups of Latino dyads had higher odds of adolescent HPV and meningococcal vaccines and higher rates of flu vaccines. Latino dyads with Spanish-preferring mothers had higher vaccination odds/rates than Latino dyads with English-preferring mothers. The effects of variation by neighborhood social deprivation in influenza vaccination rates were minor in comparison to differences by ethnicity/language concordance. CONCLUSION: In a multistate analysis of vaccinations among Latino and non-Latino adolescents, English-preferring adolescents with Spanish-preferring mothers had the highest completion rates and English-preferring non-Hispanic white dyads the lowest. Further research can seek to understand why this language dyad may have an advantage in adolescent vaccination completion.

Latino adolescents may face numerous barriers to preventive care­especially routine immunizations, but analyses often focus on single or few factors that may affect the utilization of these services. Our analysis of not only the language preference of Latino adolescents, but the preferred language of their mothers and their neighborhood social adversity demonstrates that English-preferring Latino adolescents with Spanish preferring mothers were most likely to utilize all immunizations we studied, and there were differences in utilization among Latino families by language concordance. This adds to our knowledge of Latino adolescent health care utilization by demonstrating the differences in Latino families, and suggesting that many of these families may have assets for service utilization from which we can learn.

A Ratiometric Fluorescent Probe for N2H4 Having a Large Detection Range Based upon Coumarin with Multiple Applications.

Although hydrazine (N2H4) is a versatile chemical used in many applications, it is toxic, and its leakage may pose a threat to both human health and environments. Consequently, the monitoring of N2H4 is significant. This study reports a one-step synthesis for coumarin-based ratiometric fluorescent probe (FP) CHAC, with acetyl as the recognition group. Selected deprotection of the acetyl group via N2H4 released the coumarin fluorophore, which recovered the intramolecular charge transfer process, which caused a prominent fluorescent, ratiometric response. CHAC demonstrated the advantages of high selectivity, a strong capacity for anti-interference, a low limit of detection (LOD) (0.16 µM), a large linear detection range (0-500 µM), and a wide effective pH interval (6-12) in N2H4 detection. Furthermore, the probe enabled quantitative N2H4 verifications in environmental water specimens in addition to qualitative detection of N2H4 in various soils and of gaseous N2H4. Finally, the probe ratiometrically monitored N2H4 in living cells having low cytotoxicity.

The Microbiota of Ixodes ricinus and Dermacentor reticulatus Ticks Collected from a Highly Populated City of Eastern Europe.

Recent investigations have examined, through sequencing the V6 region of 16S rRNA gene, the microbiota of questing Ixodes ricinus and Dermacentor reticulatus ticks collected from rural areas of Central (Dnipropetrovs'k (region D) and Poltava (region P)) and Northeastern (Kharkiv (region K)) Ukraine. In addition to defining the bacterial microbiota of both tick species, the previous investigations also revealed a high degree of inter-sex and inter-regional variations in the tick microbiota. As a continuation of the two studies, the present investigation has analyzed individual microbiota of questing I. ricinus (n = 50) and D. reticulatus (n = 50) ticks originating from Kyiv, the largest city of Ukraine. The Kyiv tick microbiota were compared between males and females for each tick species. Additionally, a cross-regional analysis was performed to compare the microbiota of Kyiv ticks to those from regions D, K, and P. Numerous statistically significant inter-sex and inter-regional variations were detected when alpha diversity, beta diversity, the bacterial relative and differential abundances were assessed. The overall results demonstrated that the microbiota of Kyiv ticks were statistically different compared to the ticks of the other three regions. Besides existing climatic and geographical differences between the four regions, the authors hypothesize that various anthropogenic factors of the megapolis (e.g., animal species translocation, land management, ecology) could have contributed to the distinct microbiota of Kyiv ticks observed in this study.

Analysis of Mechanism of Action of Cuprous Oxide Nanoparticles in Treatment of Cervical Cancer under Real-time Ultrasound Elastography.

It aimed to explore the adoption value of cuprous oxide nanoparticles (Cu2O NPs) in the clinical treatment of cervical cancer under the evaluation of real-time ultrasound elastography. In this experiment, the solution of Cu2O NPs was synthesized and used in 90 selected mouse models of cervical cancer. It was found that Cu2O NPs can significantly control the reproduction of various types of cervical cancer cells, effectively stopping the cycle of cervical cancer cell lines in the G1/G0 phase. In addition, the tumor weight of 0.25g in the Cu2O NPs group was notably lighter than that of 1.1g in the control group. The weight change of the mouse was 21g compared with 15g of the cis-dichlorodiamine platinum (CDDP) group, and it was proved that Cu2O NPs were less cytotoxic to the body and have few side effects. Moreover, real-time ultrasound elastography showed that there were 26 cases with a tumor elasticity score no less than 2 in the Cu2O NPs group, accounting for 87%, which was better than that of the CDDP group (17 cases, 57%), and the difference was substantial (P<0.05). The shear wave velocity of Cu2O NPs (1.46±0.48 m/s) was also lower than that (1.73±0.62 m/s) of the CDDP group, which suggested that the tumor body hardness of mice in the Cu2O NPs group was lower, and the difference was considerable (P<0.05). In short, Cu2O NPs had good functions such as inhibiting the proliferation and spread of tumor cells and blocking the cell cycle. Moreover, the toxic and side effects of the drug were slight, and it was an ideal new type of treatment for cervical cancer.

Assessment of heavy metals should be performed before the development of the selenium-rich soil: A case study in China.

The use of selenium (Se)-rich soils in China is an effective method for rural revitalization, but assessment of heavy metals is essential prior to the development of Se-rich soils. This study was focused on the Jiangjin district, a typical Se-rich area located in Sichuan Basin of China, to investigate contamination, influencing factors, and sources of As, Cr, Cu, Cd, Ni, Pb, Sb, and Zn based on 156 topsoil samples. This study analyzed and compared the enrichment factor (EF), Nemerow index (PN), geographical information system (GIS), and positive matrix factorization (PMF). Results demonstrate that the average values of As, Cu, Cd, Sb, and Zn in topsoil were higher than the soil background values of western Chongqing by approximately 1.75, 1.11, 1.27, 1.71, and 2.58 times, respectively, indicating that some heavy metals have been enriched in the soils. The polluted areas of As, Cu, Cd, and Zn in topsoil were mainly distributed in the northern and central Jiangjin district, whereas high-Sb soils were located in the southeast. The Cr, Cu, Cd, Pb, and Sb were concentrated in Se-rich soils, indicating that heavy metals pollution should be carefully considered for the utilization of Se-rich soils. Four potential sources of heavy metals were found in this study area: 1) the parent materials (Cr, Ni, Cu); 2) industrial activities with high coal consumption (As); 3) mechanical and chemical industrial activities (Zn, Sb); and 4) transportation and agricultural activities (Pb, Cd). These observations provide a scientific basis for the development, utilization, and protection of Se-rich soil resources.

Oral health needs of U.S. children with developmental disorders: a population-based study.

BACKGROUND: Children with Special Health Care Needs (CSHCN) have higher rates of oral diseases and tooth decay compared with the general population. Children with developmental disorders/ disabilities (DD) are a subset of CSHCN whose oral health has not been specifically addressed. Therefore, this study had two objectives: to describe the oral health needs (OHN) of children with DD compared with children without DD; and to assess barriers to access to care, utilization of dental services, and their association with oral health needs for children with DD. METHODS: This cross-sectional study utilized a sample of 30,530 noninstitutionalized children from the 2018 National Survey of Children's Health (NSCH). Analysis was conducted using descriptive and inferential statistics. RESULTS: The analysis identified 6501 children with DD and 24,029 children without DD. Children with DD had significantly higher prevalence of OHN (20.3% vs. 12.2%, respectively), unmet dental needs (3.5% vs 1.2%), and utilization of any dental visits (86.1% vs 76.1%), (P-value < . 001). The adjusted logistic model identified four factors that contributed to the higher odds of OHN among children with DD: poverty (< 100% of the Federal Poverty Level (AOR = 2.27, CI: 1.46-3.51), being uninsured (AOR = 2.12, 95% CI: 1.14-3.95), a high level of disability (AOR = 1.89, CI: 1.23-2.78), and living in the western United States (AOR = 1.61, CI: 1.09-2.37. CONCLUSION: Despite higher utilization of dental services, children with DD had poorer oral health and more unmet dental needs than children without DD. Advocacy efforts and policy changes are needed to develop affordable access that assesses, as early as possible, children with DD whose conditions impact their ability a great deal so that their potential OHN may be alleviated more effectively.

Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based "combo" nanoagent together with PD-L1 blockade in reversing multidrug resistance.

BACKGROUND: Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. RESULTS: In this study, we fabricated a "combo" nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. CONCLUSION: This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.

BACKGROUND: Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS: Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION: "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tß4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tß4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tß4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tß4 (rhTß4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTß4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTß4 to the treatment of human CoV diseases such as COVID-19.

Serological prevalence of six vector-borne pathogens in dogs presented for elective ovariohysterectomy or castration in the South central region of Texas.

BACKGROUND: Most vector-borne pathogens cause zoonotic diseases. These zoonoses often have wild animal reservoirs that play a significant role in disease epidemiology. However, pet animals have also been implicated in transmission of zoonotic agents to humans. To exemplify, dogs are competent reservoir hosts for several zoonotic vector-borne bacteria and protozoa. Despite that vector-borne diseases can be life-threatening for both pets and humans, studies on pathogen seroprevalence are very limited. Therefore, the objective of this study was to determine the serological prevalence of six zoonotic vector-borne agents in dogs from the South Central region of Texas (US). Electronic medical records of dogs, presenting over 2014-2019 for elective ovariohysterectomy or castration at a high volume spay and neuter clinic, were reviewed for serological testing. Sera from 418 dogs were tested for the Dirofilaria immitis antigen, and antibodies to Anaplasma phagocytophilum, Anaplasma platys, Borrelia burgdorferi, Ehrlichia canis, and Ehrlichia ewingi, using a commonly available commercial test kit. Descriptive statistics were computed to characterize the respective seroprevalence rates of the dog population. The study involved 192 (46%) male and 226 (54%) female dogs. RESULTS: Overall, 85 (20%) dogs tested positive for at least one of the 6 pathogens investigated. The highest seroprevalence rate averaged over the 6-year period was 11.7% for D. immitis followed by 8.4% for E. canis and/or E. ewingii, 4.3% for A. phagocytophilum and/or A. platys, and 0.2% for B. burgdorferi. The co-exposure or co-infection was only detected in 3.8% of the dog population. CONCLUSIONS: Together, opportunistic testing of dogs presenting for elective surgical procedures may provide an effective way of assessing seroprevalence and/or risk factors for common vector-borne diseases within a geographic region of concern.