This study elucidates the impact of element dose during nanoparticle (NPs) synthesis on plant growth indices. Novel NPs containing two essential micro-nutrients, zinc (Zn) and manganese (Mn), were co-doped on cerium oxide (CeO2) (ZnMnCe) with different ratios (1, 2, and 3%). The synthesized NPs were characterized by advanced analytical techniques (EDX, TEM, SEM, XPS, and XRD) and hydroponically applied to barley (Hordeum vulgare L.). The impact of ZnMnCe NPs on growth indices and plant nutrients was examined. SEM, HRTEM, and confocal microscopy were used to show the morphological and structural influences of ZnMnCe NPs. Results showed that the plant growth indices (root/leaf length, chlorophyll fluorescence, pigmentation, and biomass) were remarkably improved with a 1% Mn/Zn addition. Conversely, growth retardation, cell membrane damage, root morphology deformation, and genotoxicity were apparent by 3% of Mn/Zn addition. Overall, a significant improvement in growth was revealed when Mn and Zn were included at 1%. However, increasing concentrations (2% and 3%) impaired the growth. These results show that the element ratio used in NPs synthesis is essential in the plant\'s physiological response. Precise adjustment of element dosage during NPs synthesis determines whether the NPs are beneficial or harmful. This must be well-balanced for nanofertilizer production and plant applications.

Cobalt (Co) contamination in soils potentially affects human health through the food chain. Although rice (Oryza sativa) as a staple food is a major dietary source of human Co intake, it is poorly understood how Co is taken up by the roots and accumulated in rice grain. In this study, we physiologically characterized Co accumulation and identified the transporter for Co2+ uptake in rice. A dose-dependent experiment showed that Co mainly accumulated in rice roots. Further analysis with LA-ICP-MS showed Co deposited in most tissue of the roots, including exodermis, endodermis and stele region. Co accumulation analysis using mutants defective in divalent cation uptake showed that Co2+ uptake in rice is mediated by the Mn2+/Cd2+/Pb2+ transporter OsNramp5, rather than OsIRT1 for Fe2+ and OsZIP9 for Zn2+. Knockout of OsNramp5 enhanced tolerance to Co toxicity. Heterologous expression of OsNramp5 showed transport activity for Co2+ in Saccharomyces cerevisiae. Co2+ uptake was inhibited by either Mn2+ or Cd2+ supply. At the reproductive stage, the Co concentration in the straw and grains of the OsNramp5 knockout lines was decreased by 41%-48% and 28%-36%, respectively, compared with that of the wild-type rice. The expression level of OsNramp5 in the roots was not affected by Co2+. Taken together, our results indicate that OsNramp5 is a major transporter for Co2+ uptake in rice, which ultimately mediates Co accumulation in the grains.

OBJECTIVE: From the perspectives of healthcare professionals (HCPs) and people with chronic obstructive pulmonary disease (COPD) known to tertiary care, what influences successful referrals to a pulmonary rehabilitation program (PRP)?
METHODS: This cross-sectional qualitative study was informed by a critical realist perspective. We purposively sampled people with COPD and HCPs who deliver COPD care and used semi-structured interviews and focus groups to explore determinants of a successful referral to a PRP. Interviews were recorded, transcribed verbatim and analysed using reflexive thematic analysis.
RESULTS: Data were available on 38 HCPs and 15 people with COPD. We generated three core themes pertaining to successful referrals. The first theme was that HCPs should be mindful of how professional responsibilities (such as their personal value and interest in a PRP, their degree of understanding of PRPs, and the organisational culture the PRPs are embedded within) shape decision-making during a therapeutic interaction. The second theme, there\'s more to me than my COPD, characterised psychological perceptions that shape a person\'s readiness to engage in a PRP. The third theme, communication is a two-way street that requires careful navigation, characterised the interpersonal dynamic between HCP and patient, and how dedicated conversations about PRPs can encourage successful referrals.
CONCLUSIONS: Therapeutic interactions that include dedicated conversations about PRPs can foster successful referrals among people with COPD. During these interactions, HCPs should take the time to understand and carefully unpack psychological perceptions whilst imparting value, interest and enthusiasm for PRPs. Doing so can shape patient engagement toward referral success.

Hydroponics combined with fugacity model was employed to investigate the kinetics of uptake, accumulation, and metabolism of organophosphate esters (OPEs) by japonica rice. The time-dependent process for uptake and accumulation of 5 OPEs and their diester-metabolites in both rice root and shoot fitted well with the pseudo-first-order kinetic model. The peak OPE accumulations in rice root and shoot were significantly positively or negatively correlated with their octanol-water partition coefficient (logKow) respectively, but not for their apparent accumulation rates. Root concentration factors (RCFs) and root-to-shoot translocation factors (TFs) of OPEs were found to be positively and negatively correlated with their logKow, respectively. Triphenyl phosphate with benzene ring substituents showed the highest RCF, but the lowest TF, because of its high potential for root adsorption due to the π electron-rich structures. Sterilized root exudates can hinder the root adsorption and absorption of OPEs from solution probably through competitive adsorption of OPEs with root surface. The first-hand transport and metabolism rates were also obtained by generating these rates to fit the dynamic fugacity model with the measurement values. The simulation indicated that the kinetics of OPE accumulation in rice plants may be controlled by multiple processes and physicochemical properties besides Kow.

BACKGROUND: Exercise Referral Schemes (ERSs) have been implemented across Western nations to stimulate an increase in adult physical activity but evidence of their effectiveness and cost-effectiveness is equivocal. Poor ERS uptake and adherence can have a negative impact on effectiveness and cost-effectiveness and, if patterned by socio-demographic factors, can also introduce or widen health inequalities. Different modes of ERS delivery have the potential to reduce costs and enhance uptake and adherence. The primary aim of this study was to examine the effect of different programmes of ERS delivery on scheme uptake and adherence. Secondary aims were to examine the effect of socio-demographic factors on scheme uptake and adherence, and the impact of delivery mode on the expected resource and corresponding costs of delivering core parts of the programme.
METHODS: This was an observational cohort study with cost analysis. Routine monitoring data covering a three-year period (2019-2021) from one large UK ERS (number of patients = 28,917) were analysed. During this period three different programmes of delivery were operated in succession: standard (all sessions delivered face-to-face at a designated physical location), hybrid (sessions initially delivered face-to-face and then switched to remote delivery in response to the Covid-19 pandemic), and modified (sessions delivered face-to-face, remotely, or a combination of the two, as determined on a case-by-case basis according to Covid-19 risk and personal preferences). Multi-level binary logistic and linear regression were performed to examine the effect of programme of delivery and socio-demographic characteristics on uptake and adherence. Cost data were sourced from regional-level coordinators and through NERS audits supplied by national-level NERS managers and summarised using descriptive statistics.
RESULTS: There was no effect of programme of delivery on scheme uptake. In comparison to those on the standard programme (who attended a mean of 23.1 exercise sessions) those on the modified programme had higher adherence (mean attendance of 25.7 sessions) while those on the hybrid programme had lower adherence (mean attendance of 19.4 sessions). Being older, or coming from an area of lower deprivation, increased the likelihood of uptake and adherence. Being female increased the chance of uptake but was associated with lower adherence. Patients referred to the programme from secondary care were more likely to take up the programme than those referred from primary care for prevention purposes, however their attendance at exercise sessions was lower. The estimated cost per person for face-to-face delivery of a typical 16-week cycle of the scheme was £65.42. The same cycle of the scheme delivered virtually (outside of a pandemic context) was estimated to cost £201.71 per person.
CONCLUSIONS: This study contributes new evidence concerning the effect of programme of delivery on ERS uptake and adherence and strengthens existing evidence concerning the effect of socio-economic factors. The findings direct the attention of ERS providers towards specific patient sub-groups who, if inequalities are to be addressed, require additional intervention to support uptake and adherence. At a time when providers may be considering alternative programmes of delivery, these findings challenge expectations that implementing virtual delivery will necessarily lead to cost savings.

BACKGROUND: Bowel cancer screening using faecal immunochemical testing is provided in the United Kingdom with the aim of reducing mortality from colorectal cancer. However, there are low participant rates among ethnic minorities across the United Kingdom. Faith-placed interventions have the potential to improve screening rates among such populations, but studies examining their effectiveness are scarce.
METHODS: We delivered a presentation on bowel cancer screening to 204 Muslims in seven mosques in East London (intervention group). All participants completed a questionnaire regarding attitudes, perceptions and knowledge of bowel cancer screening before and after the presentation. Concurrently, we administered the questionnaire to 72 subjects attending a mosque that did not receive the presentation (comparison group).
RESULTS: The intervention group showed a greater willingness to do the test (90% vs. 67%, p < 0.001) and to recommend it to others (96% vs. 74%, p < 0.001), ability to complete the test by themselves (94% vs. 56%, p < 0.001) and confidence in noticing symptoms (78% vs. 32%, p < 0.001) after the presentation compared to before. There was a significant difference between the intervention group post-presentation and the comparison group on intention to do the test (90% vs. 79%, p = 0.02), recommending it to others (96% vs. 83%, p < 0.001), and confidence in their ability to complete the test by themselves (94% vs. 63%, p < 0.001).
CONCLUSIONS: A culture-sensitive, faith-placed health education intervention delivered in mosques can substantially improve knowledge of bowel cancer screening and increase the intention to participate in the screening programme.
UNASSIGNED: The intervention presentation was developed using insights from four public involvement sessions with four to six members representative of the East London Muslim community. The sessions sought attendees\' thoughts on appropriate ways to approach the intervention design for their community and asked for their views on the acceptability, appropriateness of messaging, format/design and likely impact of the presentation. Their views were then utilised to improve the presentation.

As a new mechanism of intercellular communication, the uptake of extracellular vesicles (EVs) by receptor cells has become a hot topic in the field. Previously, research on the uptake of EVs has focused on the mechanism of small EVs (sEVs, also known as exosomes). As sEVs represent a mixed heterogeneous population, the issue of whether there are different uptake mechanisms for different subsets of sEVs by recipient cells urgently need to be addressed. There are EVs in follicular fluid, which play an important role in the communication between follicular cells and the development of oocytes. Previously, we isolated two subtypes of sEVs in follicular fluid: low density-sEVs (LD-sEVs) and high density-sEVs (HD-sEVs). The current study aimed to explore the uptake characteristics of these two subtypes of sEVs by granulosa cells. First, PKH67 was used to label the two sEVs subtypes, and we observed their uptake by granulosa cells using confocal microscopy and flow cytometry. We then explored the specific mechanisms underlying uptake of these two sEV subtypes by granulosa cells using specific inhibitors and RNA interference. The results showed that granulosa cells took up both kinds of sEVs through a clathrin-independent pathway. In addition to requiring caveolin, cholesterol, and Na+/H+ exchange, the uptake of HD-sEVs also depended on the activity of tyrosine kinase and phosphoinositide 3-kinase. A better understanding of the mechanism of granulosa cell uptake of different subtypes of sEVs in follicular fluid is of considerable significance leading to more accurate use of EVs for targeted treatment of infertility and other related diseases.

UNASSIGNED: Achieving the 95-95-95 targets require an efficient and innovative person-centered approach, specifically community-based differentiated service delivery (DSD), to improve access to human immunodeficiency virus (HIV) services and reduce burdens on the health system. Therefore, this study aimed to assess the uptake of community-based DSD models and associated factors among people living with HIV (PLHIV).
UNASSIGNED: A multicenter cross-sectional study was conducted among PLHIV in public health facilities in South Ethiopia. Data were collected and entered into EpiData version 3.1 before being exported to Stata version 14 for further analysis. In the bivariable logistic regression analysis, variables with a p-value of ≤0.25 were included in the multivariable logistic regression analysis. A p-value of <0.05 was used to identify statistically significant factors.
UNASSIGNED: Among 381 stable PLHIV, 55.91% were women. The median age (interquartile range) was 40 years (27-53). The uptake of community-based DSD models was 19.16%. Residence and disclosure were the two independent factors significantly associated with the uptake of community-based DSD models.
UNASSIGNED: One out of five stable PLHIV on antiretroviral therapy uptake the community-based DSD models. Improvement in uptake is needed in Ethiopia\'s resource-limited healthcare system to better achieve the 95-95-95 targets.

Aconitate decarboxylase-1 (ACOD1) is expressed by activated macrophages and generates itaconate that exerts anti-microbial and immunoregulatory effects. ACOD1-itaconate is essential for macrophage-mediated control of the intracellular pathogen Coxiella (C.) burnetii, which causes Q fever. Two isomers of itaconate, mesaconate and citraconate, have overlapping yet distinct activity on macrophage metabolism and inflammatory gene expression. Here, we found that all three isomers inhibited the growth of C. burnetii in axenic culture in ACCM-2 medium. However, only itaconate reduced C. burnetii replication efficiently in Acod1-/- macrophages. In contrast, addition of citraconate strongly increased C. burnetii replication in Acod1+/- macrophages, whereas mesaconate weakly enhanced bacterial burden in Acod1-/- macrophages. Analysis of intracellular isomers showed that exogenous citraconate and mesaconate inhibited the generation of itaconate by infected Acod1+/- macrophages. Uptake of added isomers into Acod1-/- macrophages was increased after infection for itaconate and mesaconate, but not for citraconate. Mesaconate, but not citraconate, competed with itaconate for uptake into macrophages. Taken together, inhibition of itaconate generation by macrophages and interference with the uptake of extracellular itaconate could be identified as potential mechanisms behind the divergent effects of citraconate and mesaconate on C. burnetii replication in macrophages or in axenic culture.

Extracellular vesicles (EVs) are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type. A variety of biomolecules, including proteins, lipids, coding and non-coding RNAs, and mitochondrial DNA, can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells, leading to alterations in the recipient cells, suggesting that EVs play an important role in intercellular communication. EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools. At present, although the mechanisms of exosome biogenesis and secretion in donor cells are well understood, the molecular mechanism of EV recognition and uptake by recipient cells is still unclear. This review summarizes the current understanding of the molecular mechanisms of EVs\' biological journey in recipient cells, from recognition to uptake and cargo release. Furthermore, we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo, which is crucial for studies applying EVs as drug-targeted delivery vehicles. Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.
胞外囊泡（EVs）是几乎所有细胞均能分泌的纳米级脂质双层囊泡，可通过将其内含的多种包括蛋白质、脂质、编码和非编码RNA、线粒体DNA等在内的生物活性分子递送到邻近和远处的受体细胞中，以改变受体细胞功能，从而实现细胞间的信息交流。EVs在生理和病理过程中均发挥着重要作用，可用于疾病诊疗。尽管EVs在供体细胞中的生物发生和分泌机制已基本清晰，但受体细胞对EVs的识别和摄取的分子机制尚不清楚。本文对EVs进入受体细胞的生物过程包括受体细胞对EVs的识别、摄取以及EVs的货物释放进行综述，并重点关注了EVs在摄取后如何通过“溶酶体逃逸”，从而释放货物，将有助于推进EVs作为药物递送载体的研究。此外，了解和控制EVs在受体细胞中的有效摄取，对阐明EVs的功能及其临床应用同样至关重要。.