Multimaterial Printing of Serpentine Microarchitectures with Synergistic Mechanical/Piezoelectric Stimulation for Enhanced Cardiac-Specific Functional Regeneration.

Recreating the natural heart's mechanical and electrical environment is crucial for engineering functional cardiac tissue and repairing infarcted myocardium in vivo. In this study, multimaterial-printed serpentine microarchitectures are presented with synergistic mechanical/piezoelectric stimulation, incorporating polycaprolactone (PCL) microfibers for mechanical support, polyvinylidene fluoride (PVDF) microfibers for piezoelectric stimulation, and magnetic PCL/Fe3O4 for controlled deformation via an external magnet. Rat cardiomyocytes in piezoelectric constructs, subjected to dynamic mechanical stimulation, exhibit advanced maturation, featuring superior sarcomeric structures, improved calcium transients, and upregulated maturation genes compared to non-piezoelectric constructs. Furthermore, these engineered piezoelectric cardiac constructs demonstrate significant structural and functional repair of infarcted myocardium, as evidenced by enhanced ejection and shortening fraction, reduced fibrosis and inflammation, and increased angiogenesis. The findings underscore the therapeutic potential of piezoelectric cardiac constructs for myocardial infarction therapy.

Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.

Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells.

BACKGROUND: Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive. METHODS: Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion. RESULTS: Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells. CONCLUSIONS: Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.

TT-type resonator-based differential photoacoustic spectroscopy for trace gas detection.

A novel TT-type resonator was proposed for the first time, to our knowledge, to realize differential photoacoustic (PA) detection for trace gas measurement. The special design of the TT-type resonator allows us to install the microphone at the resonant center of the acoustic field to maximize the use of the absorption-induced PA signal. To meet the requirement of low gas consumption and easy integration, the TT-type resonator-based PA cell was fabricated as a fiber-coupled module with an inner volume of only 1.1 ml. For validation, the TT-type PA cell was integrated to a photoacoustic spectroscopy (PAS) system for acetylene detection. As a result, a linearity of 0.99999 was achieved in a concentration range from 0 to 5000 ppm with a noise equivalent sensitivity of 101 ppb. The proposed TT-type resonator contributes a new style of PA cell structure to the field of PAS gas detection, combining the advantages of easy integration, low gas consumption, differential detection, and photoacoustic enhancement together.

Simultaneous detection of greenhouse gases CH4 and CO2 based on a dual differential photoacoustic spectroscopy system.

In addition to the atmospheric measurement, detection of dissolved carbon oxides and hydrocarbons in a water region is also an important aspect of greenhouse gas monitoring, such as CH4 and CO2. The first step of measuring dissolved gases is the separation process of water and gases. However, slow degassing efficiency is a big challenge which requires the gas detection technology itself with low gas consumption. Photoacoustic spectroscopy (PAS) is a good choice with advantages of high sensitivity, low gas consumption, and zero background, which has been rapidly developed in recent years and is expected to be applied in the field of dissolved gas detection. In this study, a miniaturized differential photoacoustic cell with a volume of 7.9 mL is designed for CH4 and CO2 detection, and a dual differential method with four microphones is proposed to enhance the photoacoustic signal. What we believe to be a new method increases photoacoustic signal by 4 times and improves the signal to noise ratio (SNR) over 10 times compared with the conventional single-microphone mode. Two distributed feedback (DFB) lasers at 1651 nm and 2004nm are employed to construct the PAS system for CH4 and CO2 detection respectively. Wavelength modulation spectroscopy (WMS) and 2nd harmonic demodulation techniques are applied to further improve the SNR. As a result, sensitivity of 0.44 ppm and 7.39 ppm for CH4 and CO2 are achieved respectively with an integration time of 10 s. Allan deviation analysis indicates that the sensitivity can be further improved to 42 ppb (NNEA=4.7×10-10cm-1WHz-1/2) for CH4 and 0.86 ppm (NNEA=5.3×10-10cm-1WHz-1/2) for CO2 when the integration time is extended to 1000 s.

Enhancing Prognosis, Quality of Life, and Psychological Well-being in Cerebral Stroke Patients through Meticulous Risk Management: A Comprehensive Study.

Background: Cerebral stroke (CS) remains a leading cause of mortality worldwide. In addition to effective treatment, nursing intervention plays a pivotal role in the rehabilitation of CS patients. Objective: This study aims to assess the impact of meticulous care integrated with risk management on rehabilitating cerebral stroke patients. The objective is to provide valuable clinical insights for the management of CS patients. Methods: A comparative observational study was conducted, including a total of 180 CS patients admitted between February 2020 and February 2022 were selected for this study. Among them, 98 patients received meticulous care combined with risk management (research group), while 82 patients underwent routine nursing intervention (control group). We analyzed the changes in the Fugl-Meyer Motor Assessment scale, National Institute of Health Stroke Scale, Activities of Daily Living scale, and Barthel Index before and after the care interventions. Additionally, we documented nursing risk events during treatment, assessed nursing quality scores, and conducted a quality-of-life survey after a one-year follow-up. Results: The research group exhibited significantly higher post-care scores in the Fugl-Meyer Motor Assessment, Activities of Daily Living, and Barthel Index, along with lower National Institute of Health Stroke Scale scores, compared to the control group (P < .05). Furthermore, the research group experienced a lower incidence of nursing risk events and demonstrated higher nursing quality (P < .05). During the prognostic follow-up, the research group displayed a superior quality of life compared to the control group (P < .05). Conclusions: Meticulous care integrated with risk management enhances the recovery of CS patients and is strongly recommended for clinical implementation.

Post-discharge care needs of the older people with hospital-associated disability: A longitudinal study.

AIMS: To investigate the change and associated factors of care needs within 6 months post-discharge in older people with hospital-associated disability, and the relationship between time-varying care needs and physical function. BACKGROUND: Older people with hospital-associated disability will have various care needs post-discharge. Understanding their care needs will help to improve their health. However, studies on this population are still limited. DESIGN: A longitudinal study. METHODS: The older people who met the inclusion and exclusion criteria were selected in 2 tertiary hospitals in Zhejiang Province, China. The questionnaire survey method was used to collect data about socio-demographic characteristics, physical function and care needs. The data of 375 older people who completed follow-up were analysed using logistic regression analysis, generalised estimating equations and generalised additive mixed model. We followed STROBE checklist for reporting the study. RESULTS: The care needs of the older people with hospital-associated disability declined unevenly, it decreased rapidly in the first three months, and then flattening out. The percentage of people with care needs in each dimension decreased over time, but daily care and rehabilitation needs were consistently more important. Socio-demographic factors and physical function had different effects on need at different time points, the physical function was the main factor among them. There were non-linear relationships between the physical function and different care needs with different inflection points. CONCLUSION: This research revealed change patterns of the care needs of older people with hospital-associated disability post-discharge and the non-linear relationship between physical function and care needs. These findings may help healthcare professionals and caregivers to provide accurate care. RELEVANCE TO CLINICAL PRACTICE: The findings can be used to identify effective approaches to address the care needs of older people with hospital-associated disability based on the time of discharge, in conjunction with age, education, and especially physical function, which will promote the justify allocation of nursing resources. What does this paper contribute to the wider global clinical community?

The effectiveness of self-management programme based on multilevel social resources utilization in diabetes mellitus patients: A randomized controlled study.

AIMS: This study aimed to test the effects of a novel diabetes self-management education (DSME) programme focused on multilevel social resources utilization on improving self-management behaviour, social resources utilization and haemoglobin Alc (HbA1c ) in patients with type 2 diabetes mellitus (T2DM). METHODS: A randomized controlled design was used. A total of 118 participants with T2DM from two communities were recruited through randomized sampling, and randomly assigned to the novel DSME group or the traditional DSME group. DSME focusing on multilevel social resources utilization was implemented in the novel DSME group. Data were collected at baseline (T0 ), at the end of the intervention (T1 ) and 3 months after the end of intervention (T2 ) from 3 March to 16 November 2014. RESULTS: Comparing these two groups, the participants in the novel DSME group reported significantly better improvement in self-management behaviour and social resources utilization at T1 and T2 (all p < 0.01). A significant difference was found in the mean improvement of HbA1c level between the two groups at T2 (p < 0.05). CONCLUSIONS: The novel DSME programme focused on multilevel social resources utilization can effectively enhance T2DM patients' self-management behaviour and social resource utilization and lower HbA1c levels. More importantly, the effects could last longer.

Beneficial effects of metformin supplementation in hypothalamic paraventricular nucleus and arcuate nucleus of type 2 diabetic rats.

Background Oxidative stress and inflammation play important roles in the development of diabetes. Metformin (MET) is considered as the first-line therapy for patients with type 2 diabetes (T2D). Hypothalamic paraventricular nucleus (PVN) and hypothalamic arcuate nucleus (ARC) are vital in obesity and diabetes. However, there have been few studies on the effects of MET on inflammatory reaction and oxidative stress in the PVN and ARC of T2D diabetic rats. Methods Male Sprague-Dawley (SD) rats were fed with high-fat diet (HFD), and intraperitoneally injected with low-dose streptozotocin (STZ, 30 mg/kg) at 6th week to induce T2D diabetes. After injection of STZ, they were fed with HFD continually. Starting from the 8th week of HFD feeding, T2D rats received intragastrical administration of MET (150 mg/kg/day) in addition to the HFD for another 8 weeks. At the end of the 15th week, the rats were anaesthetized to record the sympathetic nerve activity and collect blood and tissue samples. Results In comparison with control rats, T2D diabetic rats had higher levels of pro-inflammatory cytokines (PICs) and excessive oxidative stress in the PVN and ARC, accompanied with more activated astrocytes. The renal sympathetic nerve activity (RSNA) and the plasma norepinephrine (NE) increased in T2D diabetic rats. The expression of tyrosine hydroxylase (TH) increased and the expression of 67-kDa isoform of glutamate decarboxylase (GAD67) decreased in T2D diabetic rats. Supplementation of MET decreased blood glucose, suppressed RSNA, decreased PICs (TNF-α, IL-1ß and IL-6) in PVN and ARC, attenuated oxidative stress and activation of astrocytes in ARC and PVN of T2D diabetic rats, as well as restored the balance of neurotransmitter synthetase. The number of Fra-LI (chronic neuronal excitation marker) positive neurons in the ARC and PVN of T2D diabetic rats increased. Chronic supplementation of MET also decreased the number of Fra-LI positive neurons in the ARC and PVN of T2D diabetic rats. Conclusion These findings suggest that the PVN and ARC participate in the beneficial effects of MET in T2D diabetic rats, which is possibly mediated via down-regulating of inflammatory molecules, attenuating oxidative stress and restoring the balance of neurotransmitter synthetase by MET in the PVN and ARC.

Application of a photoelectric magnifier to nasal injury in preterm infants receiving non-invasive ventilation: A prospective observational study.

PURPOSE: This study was to explore a photoelectric magnifier assessing nasal injury in preterm infants receiving non-invasive ventilation (NIV) treatment, and to describe the occurrence status and risk factors of nasal injuries. DESIGN: A prospective observational study. SUBJECTS: and setting: Preterm infants admitted from the Second Affiliated Hospital of Wenzhou Medical University between October 2018 and October 2019. METHODS: A continuously convenient sample of 127 preterm infants was included. When the infants were receiving NIV treatment, nursing staff checked nasal skin and mucosa daily with a photoelectric magnifier to confirm whether nasal injuries occurred. Meanwhile, a self-designed questionnaire was used to collect data. The Chi-square test, t-test, univariate and multiple logistic regression model were applied. RESULTS: A total of 127 preterm infants received 175 times NIV therapy, showing that the incidence of nasal injuries (infants number) was 27.6% (35/127) and the incidence of nasal injuries (ventilation cases) was 21.1% (37/175). Of the 37 cases of nasal injuries, 27 cases were I stage, while Ⅱ stage, Ⅲ stage and mucosa injuries appeared 2 cases, 2 cases and 6 cases. In the multivariate logistic analysis, nasal mask interface and NIV treatment more than seven days were independent risk factors affecting the occurrence of nasal injuries. CONCLUSIONS: The premature infants who received nasal NIV treatment were susceptible to nasal injuries, and clinical nurse capable of identifying risk factors and inintervening should be strengthened to prevent the occurrence and progression.

Recent Advances in Transition-metal-catalyzed C-C Bond Formation via C(sp2 )-F Bond Cleavage.

The activation of a carbon-fluorine bond is one of the most challenging topics in modern synthetic organic chemistry due to their low reactivity compared to other carbon-halogen bonds. In this review, we present the recent developments since 2015 on cross-coupling reactions that form C-C bonds via cleavage of C(sp2 )-F bonds. Not only the conventional activation of C(sp2 )-F bonds, but also decarbonylative or carbonyl-retentive cleavage of C(acyl)-F bonds will be introduced. This paper mainly describes new protocols for the formation of C(sp2 )-C(sp3 ), C(sp2 )-C(sp2 ), and C(sp2 )-C(sp) bonds via transition-metal-catalyzed cleavage of C(sp2 )-F bonds.

Chronic Infusion of Astaxanthin Into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates the Renin-Angiotensin System in Spontaneously Hypertensive Rats.

ABSTRACT: Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 µL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1ß, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats.

BACKGROUND: Inflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. METHODS: Prehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively. RESULTS: NLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3. CONCLUSIONS: Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.

Lipid Biomarkers in Acute Myocardial Infarction Before and After Percutaneous Coronary Intervention by Lipidomics Analysis.

BACKGROUND Reperfusion injury is one of the leading causes of myocardial cell death and heart failure. This study was performed to identify new candidate lipid biomarkers for the purpose of optimizing the diagnosis of myocardial ischemia reperfusion (I/R) injury, assessing the severity of myocardial I/R injury and trying to find the novel mechanism related to lipids. MATERIAL AND METHODS Forty patients who were diagnosed with ST-segment elevation myocardial infarction (STEMI) were randomly selected for this study. Serum samples from all the patients with STEMI were collected at 3 time periods: after STEMI diagnosis but prior to reperfusion (T0); and then at 2 hours (T2) and 24 hours (T24) after the end of the percutaneous coronary intervention procedure. Plasma lipidomics profiling analysis was performed to identify the lipid metabolic signatures of myocardial I/R injury using lipidomics. RESULTS Sixteen types of potential lipid biomarkers at different time periods (T0, T2, T24) were identified by using lipidomics technology. The T0 time periods exhibited 16 differentially metabolized lipid peaks in the patients after STEMI diagnosis but prior to reperfusion. With the increase of reperfusion times, the contents of these 16 lipid biomarkers decreased gradually, but there was a 1.5- to 2-fold increase of those 16 lipid biomarkers contents at T2 compared with T24. CONCLUSIONS Lipidomics analysis demonstrated differential change before and after reperfusion, suggesting a potential role of some of these lipids as biomarkers for optimizing the diagnosis of myocardial I/R, as well as for therapeutic targets against myocardial I/R injury.

Post-Traumatic Stress Disorder and It's Predictors Among Tibetan Adolescents 3Years After the High-Altitude Earthquake in China.

This study examined post-traumatic stress disorder(PTSD) and it's predictors among 4072 Tibetan adolescents 3years after the highaltitude earthquake. The instruments included The PTSD Checklist-Civilian version, The Internality, Powerful others, and Chance Scale and The Coping Style Scale. The results indicated the prevalence rate of probable PTSD was 17.8%.The predicting factors for PTSD were found to being aged 14 or older, being senior student, being monitor, being buried/injured, have family member died/amputated, have severer property loss, have witnessed death, have negative coping skills, and have power others locus of control. Effective mental health services should be developed to facilitate post-disaster recovery.

Cross-cultural adaptation and validation of the positive and negative social exchange scale in older adults with disabilities in China.

PURPOSE: This study translated the Positive and Negative Social Exchange (PANSE) scale into Chinese, examined its psychometric characteristics, and explored its feasibility for use among older adults with disabilities from China. MATERIALS AND METHODS: A two-stage study procedure was employed. In the first stage, the English version of the PANSE scale was translated and cross-culturally adapted. In the second stage, the reliability and validity of the scale were assessed based on item-total correlation, internal consistency, test-retest reliability, content validity, structural validity, concurrent criterion validity, and known group validity. RESULTS: A total of 357 older adults with disabilities participated in the survey. The Chinese version of the PANSE scale consisted of two parts, the Positive Social Exchange Scale and the Negative Social Exchange Scale. Exploratory factor analysis extracted six communal factors. The cumulative contribution of the two parts of the scale was 69.90% and 77.88%, respectively. The item-total correlation was 0.353 to 0.802, the internal consistency of the PANSE was 0.653 to 0.886. The PANSE demonstrated good content validity and it was correlated with the SSRS scale. CONCLUSION: The Chinese version of the PANSE is a valid and reliable instrument for assessing social exchange in Chinese older adults with disabilities.Implication for rehabilitationDespite the growing number of older adults with disabilities being a concern in China, the lack of tools to measure the type of social support limits research related to the health status of these people.This study cross-culturally adapted, translated into Chinese and validated the Positive and Negative Social Exchange (PANSE) scale as the measurement tool to be used in the cultural context of China.The two subscales of PANSE were validated in the Chinese population of older adults with disabilities.The PANSE scale measures social exchange among older adults with disabilities in China, which can guide the development of interventions to address issues in the social exchange of these people.

Dysregulated T-cell homeostasis and decreased CD30+ Treg proliferating in aplastic anemia.

Aplastic anemia (AA) is an autoimmune hematopoietic disease mediated by autoreactive T cells leading to bone marrow failure. However, the precise role of autoreactive T cells in the development of AA is not fully understood, hindering the advancement of therapeutic and diagnostic strategies. In this study, we conducted a single-cell transcriptome analysis of CD8+ T cells, conventional CD4+ T (CD4+ Tconv) cells, and Treg cells, to elucidate the potential disruption of T cell homeostasis in patients with AA. We identified changes in CD4+ Tconv cells, including loss of homeostasis in naïve and memory cells and increased differentiation potential in T helper type 1 (TH1), T helper type 2 (TH2), and T helper type 17 (TH17) cells. Additionally, we identified naïve and memory CD8+ T cells that were enforced into an effector state. CD127 is an ideal surface marker for assessing the immune state of CD8+ T cells，as identified by flow cytometry. Abnormal expression of TNFSF8 has been observed in AA and other autoimmune diseases. Flow cytometry analysis revealed that TNFRSF8 (CD30), a receptor for TNFSF8, was predominantly present in human Treg cells. Importantly, patients with AA have a decreased CD30+ Treg subset. RNA-sequencing analysis revealed, that the CD30+ Treg cells are characterized by high proliferation and a remarkable immunosuppressive phenotype. Taken, together, we propose that abnormal TNFSF8/TNFRSF8 signaling is involved in dysfunctional T cell immunity by increasing the destruction of CD30+ Treg cells.

Identification and characterization of three monoclonal antibodies targeting the SFTSV glycoprotein and displaying a broad spectrum recognition of SFTSV-related viruses.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13-30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses.

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus.

Background: Long term hypertension seriously promotes target organ damage in the brain and heart, and has increasingly become serious public health problem worldwide. The anti-hypertensive effects of capsaicin has been reported, however, the role and mechanism of capsaicin within the brain on salt-induced hypertension have yet to be elucidated. This study aimed to verify the hypothesis that capsaicin attenuates salt-induced hypertension via the AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus (PVN). Methods: Dahl salt-sensitive (Dahl S) rats were used as animal model for the present study. Rats were randomly divided into four groups based on their dietary regimen (0.3% normal salt diet and 8% high salt diet) and treatment methods (infusion of vehicle or capsaicin in the PVN). Capsaicin was chronically administered in the PVN throughout the animal experiment phase of the study that lasted 6 weeks. Results: Our results demonstrated that PVN pretreatment with capsaicin can slow down raise of the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats given high salt diet. Interestingly, the cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in the expression of mRNA expression of NADPH oxidase-2 (NOX2), inducible nitric oxide synthase (iNOS), NOX4, p-IKKß and proinflammatory cytokines and increase in number of positive cell level for Nrf2 and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were decreased, phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were increased after the PVN pretreatment with capsaicin. Conclusion: Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.

Puerarin Alleviates Blood Pressure via Inhibition of ROS/TLR4/NLRP3 Inflammasome Signaling Pathway in the Hypothalamic Paraventricular Nucleus of Salt-Induced Prehypertensive Rats.

BACKGROUND: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. PURPOSE: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. METHODS: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. RESULTS: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. CONCLUSION: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.