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Blood–brain barrier (BBB) dysfunction is a key feature in neuroimmunological and neurodegenerative diseases. In this study, we developed a microfluidic human BBB-on-a-chip to model barrier dysfunction and immune cell migration using immortalized TY10 brain endothelial cells, pericytes, and astrocytes. It was found that immortalized TY10 brain endothelial cells developed a microvascular structure under flow. Pericytes were localized on the basal side surrounding the TY10 microvascular structure, showing an in vivo-like structure. Barrier integrity increased under co-culture with pericytes. In addition, both ethylenediaminetetraacetic acid (EDTA) and anti-Claudin-5 (CLDN5) neutralizing antibody caused a decrease in the transendothelial electrical resistance (TEER). EDTA caused the leakage of 20 kDa dextran, suggesting different effects on the BBB based on the mechanism of action, whereas anti-CLDN5 antibody did not cause leakage. In the tri-culture model, human T cells migrated through endothelial vessels towards basal C-X-C motif chemokine ligand 12 (CXCL12). The live-imaging analysis confirmed the extravasation of fluorescence-labelled T cells in a CXCL12-concentration- and time-dependent manner. Our BBB model had an in vivo-like structure and successfully represented barrier dysfunction and transendothelial T cell migration. In addition, our study suggests that the inhibition of CLDN5 attenuates the BBB in humans. This platform has various potential uses in relation to the BBB in both drug discovery research and in elucidating the mechanisms of central nervous system diseases.

Alzheimer’s disease (AD) is a neurological disease, and its signs and symptoms appear slowly over time. Although current Alzheimer’s disease treatments can alleviate symptoms, they cannot prevent the disease from progressing. To accurately diagnose and treat Alzheimer’s disease, it is therefore necessary to establish effective methods for diagnosis. Apolipoprotein E4 (ApoE4), the most frequent genetic risk factor for AD, is expressed in more than half of patients with AD, making it an attractive target for AD therapy. We used molecular docking simulations, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations to investigate the specific interactions between ApoE4 and the naturally occurring compounds found in the plant Moringa Oleifera. According to the FMO calculations, quercetin had the highest binding affinity to ApoE4 among the sixteen compounds because its hydroxyl groups generated strong hydrogen bonds with the ApoE4 residues Trp11, Asp12, Arg15, and Asp130. As a result, we proposed various quercetin derivatives by introducing a hydroxyl group into quercetin and studied their ApoE4 binding properties. The FMO data clearly showed that adding a hydroxyl group to quercetin improved its binding capacity to ApoE4. Furthermore, ApoE4 Trp11, Asp12, Arg15, and Asp130 residues were discovered to be required for significant interactions between ApoE4 and quercetin derivatives. They had a higher ApoE4 binding affinity than our previously proposed epicatechin derivatives. Accordingly, the current results evaluated using the ab initio FMO method will be useful for designing potent ApoE4 inhibitors that can be used as a candidate agent for AD treatment.

All stakeholders, especially households that depend on agriculture, must come up with every avenue available to improve farm productivity in order to raise yields due to the constraints posed by climate change on food production systems. Sufficient increments in yields will address the challenges of food insecurity and malnutrition among vulnerable households, especially smallholder ones. Yield increases can be achieved sustainably through the deployment of various Climate Smart Integrated Pest Management (CS-IPM) practices, including good agronomic practices. Therefore, CS-IPM practices could be essential in ensuring better household welfare, including food security and nutrition. With such impact empirically documented, appropriate policy guidance can be realized in favor of CS-IPM practices at scale, thus helping to achieve sustainable food security and food systems. However, to this end, there is yet limited evidence on the real impact of CS-IPM practices on the various core social welfare household parameters, for instance, food security, household incomes, gender roles, and nutrition, among others. We contribute to this body of literature in this paper by reviewing various empirical evidence that analyzes the impact of respective CS-IPM practices on key social welfare aspects of smallholder farm households in developing countries around the world. The review finds that CS-IPM practices do increase households’ adaptation to climate change, thus enhancing soil and crop productivity, thereby ensuring food and nutrition security, as well as increasing market participation of CS-IPM adopters, thus leading to increased household incomes, asset accumulation, and subsequently better household food and nutrition security via direct own-farm produce consumption and market purchases using income. CS-IPM practices also enhance access to climate-related information, reduce greenhouse gas emissions, conserve biodiversity, and enhance dietary diversity through improved crop and livestock varieties and also reduce variable farm production costs. Therefore, there would be multiple welfare gains if CS-IPM practices were scaled up.

One of the most severe side effects of photoimmunotherapy (PIT) for head and neck cancer is pain. As there are presently no detailed reports on pain and pain management in PIT, we conducted a retrospective case series study. We conducted a retrospective study of five patients who had received PIT at the National Cancer Center Hospital East between January 2021 and June 2022 using medical chart data. All patients experienced pain, evidenced by an increased numerical rating scale (NRS) after PIT, regardless of the illumination method. The daily change in mean NRS rating shows that the pain was highest on the day of PIT, with ratings of 6.8 and 7.8 for the frontal and cylindrical diffuser methods, respectively; it dropped the following day quickly. Four of the five patients received fentanyl injections for postoperative pain management beginning on postoperative day (POD) 0. All patients who underwent therapy using a cylindrical diffuser required postoperative pain management with opioid drugs. Pain after PIT tended to be most intense immediately after or one hour after illumination and declined the following day, suggesting the need to have a pain relief plan in place in advance.

This study examined the determinants and impacts of mobile money (MM) usage on maize productivity and poverty likelihood (i.e., the probability of a household falling below the international poverty line at USD 1.9 per capita per day) in the Mbeya Region, Tanzania. The analysis was conducted using the endogenous switching regression (ESR) model on data from a random sample of 1310 households selected from seven districts in the region. Results of the ESR estimation show that MM usage is strongly and positively associated with the education level of the household head, asset ownership, credit access, input access, and social networks. MM usage is also significantly associated with increased maize productivity and a reduced poverty likelihood. Farmers who chose to use MM services increased their maize productivity by about 124 kg/acre and reduced their poverty likelihood by nearly 25 percentage points, as measured by the progress out of poverty index. These findings call for a targeted approach to reaching and supporting MM usage among households with constrained access to formal financial services to increase maize productivity and reduce poverty likelihood.

Accumulating evidence in tissues suggests an interconnection between circadian clocks and redox regulation. Diurnal variations in antioxidant levels, circadian rhythms of antioxidant enzyme activity, and differences in oxidative stress markers at different times of the day all indicate that oxidative stress responses follow a circadian rhythm. Disruptions of circadian rhythms are linked to a number of age-related diseases, including those in the eye. Typically, ocular tissues contain a robust antioxidant defence system to maintain redox balance and minimise oxidative stress and damage. The lens, in particular, contains remarkably high levels of the antioxidant glutathione (GSH). However, with advancing age, GSH levels deplete, initiating a chain of biochemical events that ultimately result in protein aggregation, light scattering, and age-related cataracts. While there is evidence that the lens exhibits circadian rhythms in the synthesis and release of melatonin, little is known about the regulation or function of timekeeping mechanisms in the lens. Since circadian rhythms are disrupted with age, and the depletion of GSH in the lens is a known initiating factor in the development of age-related cataracts, understanding the mechanisms involved in regulating GSH levels may lead to the future development of approaches to manipulate the clock to restore GSH levels and redox balance in the lens, and protect the lens from cataracts.

Following the development and dissemination of new climate-smart agricultural technologies to farmers globally, there has been an increase in the number of socio-economic studies on the adoption of climate-smart integrated pests’ management (CS-IPM) technologies over the years. In this study, we review empirical evidence on adoption determinants of CS-IPM technologies and identify possible science–policy interfaces. Generally, our review shows that socioeconomic and institutional factors are influential in shaping CS-IPM adoption decisions of farmers. More specifically, income was found to positively influence the adoption of CS-IPM technologies while land size owned influences CS-IPM adoption negatively. Registered land tenure (registered secure rights) positively influences CS-IPM technologies’ adoption, implying that efficient land markets enable competitive and fair distribution and access to land, more so by the vulnerable but efficient smallholder producers that do indeed increase the adoption of CS-IPMs technologies. Social capital, achieved via farmers’ organizations is also central in fostering CS-IPM technologies’ adoption, just as market reforms that minimize market failures regarding access to credit, labor, and agricultural information, which could indirectly hinder farmers’ use of CS-IPM practices. Functional extension systems that improve farmers’ awareness of CS-IPM do also improve CS-IPM technologies’ adoption. However, the adoption of CS-IPM technologies in Ghana and Benin is slow-paced because of factors like lack of access to farm inputs that facilitate uptake of these technologies, lack of credit facilities, and limited extension services, among others. Interestingly, our review confirms that CS-IPM technologies do indeed reduce and minimize the intensity of pesticide usage and foster ecosystem (environmental and human) health. Therefore, this review unearths strategic determinants of CS-IPM adoption and makes fundamental guidance around climate-smart innovations transfer and environmental policies that should be prioritized to curb environmental pollution and ensure agricultural ecosystems’ sustainability.

Climate-Smart Agriculture (CSA) is an approach that identifies actions needed to transform and reorganize agricultural systems to effectively support agricultural development and ensure food security in the face of climate change. In this study, we assessed farmers’ perception of climate change, available CSA practices (CSAP) and the determinants of CSAP adoption in northern Benin. A list of CSAP was generated from a workshop with different stakeholders. Face-to-face interviews were then carried out with 368 farmers selected based on stratified random sampling in the study area. Binomial generalized mixed-effect models were run to analyze the relation between socio-demographic characteristics and the use of CSAP. CSAP were evaluated using a three-point Likert scale and the frequency of agreement with the statement that the selected practices meet the pillars of CSA. More than 60% of farmers had heard about climate change, and more than 80% had observed changes in temperature, rainfall amounts and distribution. Thirty-one CSAP were identified in the area, and only 11 were known by more than 50% of farmers. Out of the 12 selected CSAP for the assessment of adoption and evaluation, seven (7) were used by more than 50% of those who knew them. Farmers agreed with the statements that the evaluated practices improved farm productivity and adaptation to climate change but did not mitigate climate change. Ethnic group and education level were the two major factors that significantly determined the use of the evaluated CSAP.

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student’s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.

We assess the validity of the surface moisture availability parameter (Mo) derived from satellite-based optical/thermal measurements using the simplified triangle method. First, we show that Mo values obtained from the simplified triangle method agree closely with those generated from a soil/vegetation/atmosphere/transfer (SVAT) model for scenes over a field site at the Allahabad district, India. Next, we compared Mo values from the simplified triangle method for these same overpass scenes with surface soil water content measured at depths of 5 and 15 cm at this field site. Although a very weak correlation exists between remotely sensed values of Mo for the full scenes and measured soil water content measured at both depths, correlations increasingly improve for the 5 cm samples (but not for the 15 cm samples) as pixels were limited to increasingly smaller vegetation fractions. We conclude that the simplified triangle method would yield reasonable values of Mo and demonstrate good agreement with ground measurements, provided that validation is limited to pixels with little or no vegetation and to soil depths of 5 cm or less.

Acute retinal necrosis (ARN) is a rare viral endophthalmitis, and human herpesvirus is the principal pathogen. Early diagnosis and treatment are critical to avoid visual impairment by ARN, and pars plana vitrectomy (PPV) is required in advanced cases. In this study, we evaluated the transition of viral load in ocular fluids of ARN eyes with varicella-zoster virus (VZV) after intravenous acyclovir treatment. Fourteen eyes of 13 patients were analyzed retrospectively. All patients received intravenous acyclovir treatment, and eventually, all eyes underwent PPV. A polymerase chain reaction (PCR) test showed a 100% detection rate in all aqueous humor samples collected before the treatment (Pre-AH), as well as aqueous humor (Post-AH) and vitreous fluid samples (VF), collected during PPV conducted after the treatment. Within eight days or less of acyclovir treatment, viral loads both in AH and VF did not decrease significantly. Furthermore, the viral load of Pre-AH had a strong correlation with that of VH. These data suggest that in ARN eyes with VZV infection, the AH sample for the PCR test was reliable to confirm the pathogen. We propose that short-term treatment of intravenous acyclovir may be insufficient for reducing intraocular viral load, and the Pre-AH sample could be a predictor of viral activity in the eyes after acyclovir treatment.

Background: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD’s usefulness if taken after a virus has already infected airway tissue. Objective: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD’s experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. Conclusion: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. Conclusion: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

The biomolecular homochirality in living organisms has been investigated for decades, but its origin remains poorly understood. It has been shown that circular polarized light (CPL) and other energy sources are capable of inducing small enantiomeric excesses (ees) in some primary biomolecules, such as amino acids or sugars. Since the first findings of amino acids in carbonaceous meteorites, a scenario in which essential chiral biomolecules originate in space and are delivered by celestial bodies has arisen. Numerous studies have thus focused on their detection, identification, and enantiomeric excess calculations in extraterrestrial matrices. In this review we summarize the discoveries in amino acids, sugars, and organophosphorus compounds in meteorites, comets, and laboratory-simulated interstellar ices. Based on available analytical data, we also discuss their interactions with CPL in the ultraviolet (UV) and vacuum ultraviolet (VUV) regions, their abiotic chiral or achiral synthesis, and their enantiomeric distribution. Without doubt, further laboratory investigations and upcoming space missions are required to shed more light on our potential extraterrestrial molecular origins.

The authors wish to make the following corrections to this paper [...]

Some of the steel slag from ironworks and dredged soils from marine and waterfront engineering work are partially treated as waste. However, a mixture of these two kinds of waste has the potential to be used as construction materials when mixed, due to chemical reactions forming secondary phases. Utilizing waste of such kind as a resource will help to improve sustainability in society by reducing waste and replacing virgin resources such as cement. Recently, it was reported that mixtures of steel slag and dredged soil hardens under specific conditions. The phase compositions of dredged soils and steel slags vary depending on the quantity of each component, which results in unpredictable strength development of mixtures. The effect of the variations in the components of steel slags and dredged soils on strength development of the mixtures is not yet clear, limiting the utilization of both materials. Understanding the hardening mechanisms of the mixtures will enable the prediction of strength development. Focusing on the variations in the components in steel slags and, especially of dredged soils, this study aims to identify the components in both materials that affect the secondary phase formation that are responsible for strength development. We found support for suggestions that calcium silicate hydrate, C-S-H, is one of the secondary phases responsible for the strength development of the mixtures. From a comparison of two kinds of steel slags and various dredged soils, the amount of portlandite in the steel slags and the amount of amorphous silica in the dredged soils are suggested as a couple of the key components of starting materials involved in the C-S-H formation.