Association between frailty index based on routine laboratory tests and risk of cerebral small vessel disease in elderly patients: a hospital-based observational study.

BACKGROUND: The association between frailty and cerebral small vessel disease (CSVD) remains controversial due to the use of different methods to assess frailty, including physical frailty phenotype and frailty scores containing measures of cognition. A frailty index based on laboratory tests (FI-Lab), which assesses frailty by the combination of routine laboratory measures and several vital signs, is independent of cognition and function status. We aimed to evaluate the association of FI-Lab with CSVD. METHODS: An observational study was carried out in a hospitalized cohort of older patients with minor ischemic stroke or TIA. The FI-Lab was constructed by 20 routine laboratory tests, plus systolic blood pressure, diastolic blood pressure, and pulse pressure. Manifestations of CSVD including white matter hyperintensity (WMH), silent lacunar infarcts, microbleed, enlarged perivascular spaces (EPVS), as well as deep brain atrophy, were measured on magnetic resonance imaging (MRI). An ordinal score system constructed by WMH, EPVS, silent lacunar infarcts, and microbleed was used to reflect the total burden of CSVD. The associations between FI-lab and CSVD were examined by logistic regression analysis and ordinal regression. RESULTS: A total of 398 patients were recruited from January 2016 to December 2018. The mean FI-Lab value was 0.26 ± 0.11. The prevalence of extensive periventricular WMH, extensive deep WMH, extensive basal ganglia EPVS, extensive centrum semiovale EPVS, silent lacunar infarcts, and deep microbleed was 26.1, 66.6, 68.6, 80.7, 32.9, and 6.5%, respectively. A higher FI-Lab value was associated with increased risks of extensive deep WMH (OR = 1.622; 95% CI, 1.253 ~ 2.100), extensive basal ganglia EPVS (OR = 1.535; 95% CI, 1.187 ~ 1.985), extensive centrum semiovale EPVS (OR = 1.584; 95% CI, 1.167 ~ 2.151), silent lacunar infarcts (OR = 1.273; 95% CI, 1.007 ~ 1.608), and higher total burden of CSVD. These associations remained after the adjustment of potential confounding factors. CONCLUSION: This study demonstrated that a higher FI-Lab score might be associated with the presence of WMH, EPVS, silent lacunar infarcts, as well as severe total CSVD burden in older patients with minor stroke or TIA. The FI-Lab provides a basis for the prediction of CSVD.

Analysis of changes in population's cross-city travel patterns in the pre- and post-pandemic era: A case study of China.

The coronavirus disease (COVID-19) outbreak has immensely changed people's travel behaviour. The changes in travel behaviour have had a huge impact on different industries, such as consumption, entertainment, commerce, office, and education. This study investigates the impact of COVID-19 on population travel patterns from three aspects: total trips, travel recovery degree, and travel distance. The result indicates that COVID-19 has reduced the total number of cross-city trips and flexible non-work travel; in the post-pandemic era, cross-city travel is mainly short-distance (distance <100 km). This study has significant policymaking implications for governments in countries where the population shares a similar change in travel behaviour.

Dual Role of Triptolide in Interrupting the NLRP3 Inflammasome Pathway to Attenuate Cardiac Fibrosis.

In a previous paper, we reported that triptolide (TP), a commonly used immunomodulator, could attenuate cardiac hypertrophy. This present study aimed to further explore the inhibition of cardiac fibrosis by TP and the possible mechanism from the perspective of the NOD-like receptor protein 3 (NLRP3) inflammasome. Hematoxylin-eosin and Masson's staining, immunohistochemistry, and immunofluorescence were performed to observe cardiac fibrotic changes in mice and mouse cardiac fibroblasts (CFs). The Western blot, colocalization, and immunoprecipitation were applied to detect protein expression and interactions. Results suggested that TP dose-dependently inhibited cardiac fibrosis induced by isoproterenol and collagen production of CFs induced by angiotensin II. TP exhibited an antifibrotic effect via inhibiting activation of the NLRP3 inflammasome, which sequentially decreased IL-1ß maturation, myeloid differentiation factor 88 (MyD88)-related phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase 1/2 (ERK1/2), and TGF-ß1/Smad signaling, and ultimately resulted in less collagen production. Moreover, TP showed no antifibrotic effect in Nlrp3-knockout CFs. Notably, TP inhibited the expression of NLRP3 and apoptosis-associated speck-like proteins containing a caspase recruitment domain (ASC) as well as inflammasome assembly, by interrupting the NLRP3-ASC interaction to inhibit inflammasome activation. Finally, TP indeed inhibited the NLRP3-TGFß1-Smad pathway in vivo. Conclusively, TP was found to play a dual role in interrupting the activation of the NLRP3 inflammasome to attenuate cardiac fibrosis.

[Research progress on pharmacokinetics and pharmacological activities of artesunate].

Artesunate (AS), a famous derivative of the artemisinin, is the basic treatment globally for mild to severe malaria infection due to the prominent advantages such as high efficiency, fast effect, low toxicity and not easy to produce resistance. More and more research reports have shown that AS and its active metabolites dihydroartemisinin (DHA) had various bioactivities in addition to antimalarial activity, attracting researchers to further study its new pharmacological effects in order to explore new use of the old drug. A comprehensive understanding of the pharmacokinetic characteristics of AS will be conducive to the further development of new pharmacological actions and clinical application of AS. Therefore, this paper would review the absorption, distribution, metabolism and excretion of AS in vivo, as well as the pharmacokinetics characteristics of AS and DHA after clinical administration of AS by intravenous (IV), intramuscular (IM), oral or rectal routes. The in vivo process and pharmacokinetic parameters of AS and DHA were compared between healthy volunteers, malaria patients, and special populations (children, women). Meanwhile, the research progress on pharmacological effects of AS and active metabolite DHA such as anti-tumor, anti-inflammatory, anti septic, antiangiogenic, anti-fibrosis and immunoregulation activities would be also reviewed, hoping to provide a theoretical basis for the further development and utilization of AS and its metabolites.

The aggregation enhanced photoluminescence of gold nanorods in aqueous solutions.

The photoluminescence (PL) properties of single gold nanorod (AuNR) under one-photon excitation (OPE) have been reported recently. In this work, the PL of AuNRs in aqueous solutions were studied with OPE of 514 or 633 nm to characterize the emissions of transverse and longitudinal surface Plasmon resonance (TSPR and LSPR) bands, because the AuNRs aqueous solution was frequently used in bio-medical applications. We found that under 514 nm OPE the TSPR emissions of four groups of AuNRs with different aspect ratios in aqueous solutions were all strong dominating the PL emission with the quantum yield (QY) of 10(-4), which is at least three orders of magnitude higher than that of single AuNR. We further found that the aggregate was the basic form of AuNRs in aqueous solution and living cells, measured by the elastic light scattering and transmission electron microscopy measurements. The Plasmon coupling particularly the TSPR coupling between the neighbored AuNRs in aggregates enhanced the PL and increased the QY, because the conjugation of the rod side to side was a main aggregate mode. Under 633 nm OPE, only LSPR emissions of AuNRs aqueous solutions occurred with the QY level of 10(-5) which is very similar to that of singe AuNR, because of the negligible LSPR coupling.

Ultra-Confined Phonon Polaritons and Strongly Coupled Microcavity Exciton Polaritons in Monolayer MoSi2N4 and WSi2N4.

The 2D semiconductors are an ideal platform for exploration of bosonic fluids composed of coupled photons and collective excitations of atoms or excitons, primarily due to large excitonic binding energies and strong light-matter interaction. Based on first-principles calculations, it is demonstrated that the phonon polaritons formed by two infrared-active phonon modes in monolayer MoSi2N4 and WSi2N4 possess ultra-high confinement factors of around ≈105 and 103, surpassing those of conventional polaritonic thin-film materials by two orders of magnitude. It is observed that the first bright exciton possesses a substantial binding energies of 750 and 740 meV in these two monolayers, with the radiative recombination lifetimes as long as 25 and 188 ns, and the Rabi splitting of the formed cavity-exciton polaritons reaching 373 and 321 meV, respectively. The effective masses of the cavity exciton polaritons are approximately 10-5me, providing the potential for high-temperature quantum condensation. The ultra-confined and ultra-low-loss phonon polaritons, as well as strongly-coupled cavity exciton polaritons with ultra-small polaritonic effective masses in these two monolayers, offering the flexible control of light at the nanoscale, probably leading to practical applications in nanophotonics, meta-optics, and quantum materials.

Spin-Orbit-Coupling-Induced Topological Transition and Anomalously Strong Intervalley Scattering in Two-Dimensional Bismuth Allotropes with Enhanced Thermoelectric Performances.

The convergence of multivalley bands is originally believed to be beneficial for thermoelectric performance by enhancing the charge conductivity while preserving the Seebeck coefficients, based on the assumption that electron interband or intervalley scattering effects are totally negligible. In this work, we demonstrate that ß-Bi with a buckled honeycomb structure experiences a topological transition from a normal insulator to a Z2 topological insulator induced by spin-orbit coupling, which subsequently increases the band degeneracy and is probably beneficial for enhancement of the thermoelectric power factor for holes. Therefore, strong intervalley scattering can be observed in both band-convergent ß- and aw-Bi monolayers. Compared to ß-Bi, aw-Bi with a puckered black-phosphorus-like structure possesses high carrier mobilities with 318 cm2/(V s) for electrons and 568 cm2/(V s) for holes at room temperature. We also unveil extraordinarily strong fourth phonon-phonon interactions in these bismuth monolayers, significantly reducing their lattice thermal conductivities at room temperature, which is generally anomalous in conventional semiconductors. Finally, a high thermoelectric figure of merit (zT) can be achieved in both bismuth monolayers, especially for aw-Bi with an n-type zT value of 2.2 at room temperature. Our results suggest that strong fourth phonon-phonon interactions are crucial to a high thermoelectric performance in these materials, and two-dimensional bismuth is probably a promising thermoelectric material due to its enhanced band convergence induced by the topological transition.

Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow-derived mesenchymal stem cells.

OY-TES-1 is a member of the CTA (cancer-testis antigen) group expressed in a variety of cancer and restrictedly expressed in adult normal tissues, except for testis. To determine whether MSCs (mesenchymal stem cells) express OY-TES-1 and its possible roles on MSCs, OY-TES-1 expression in MSCs isolated from human bone marrow was tested with RT (reverse transcription)-PCR, immunocytochemistry and Western blot. Using RNAi (RNA interference) technology, OY-TES-1 expression was knocked down followed by analysing cell viability, cell cycle, apoptosis and migration ability. MSCs expressed OY-TES-1 at both mRNA and protein levels. The down-regulation of OY-TES-1 expression in these MSCs caused cell growth inhibition, cell cycle arrest, apoptosis induction and migration ability attenuation. Through these primary results it was suggested that OY-TES-1 may influence the biological behaviour of MSCs.

Subclinical hypothyroidism is associated with basal ganglia enlarged perivascular spaces and overall cerebral small vessel disease load.

BACKGROUND: The association between subclinical hypothyroidism (SCH) and cerebral small vessel disease (CSVD) in the stroke-free population is currently unclear. METHODS: A total of 354 individuals without a history of stroke were enrolled in this study. Demographic data, medical history, vascular risk factors, carotid arteriosclerosis, and the results of laboratory tests were collated. SCH is defined as an elevation in thyroid-stimulating hormone levels, but with normal free thyroxine levels. Magnetic resonance imaging (MRI) was used to assess 4 markers of CSVD, including white matter hyperintensities (WMHs), lacunes, deep microbleeds, and enlarged perivascular spaces (EPVSs). The overall CSVD load was then ranked using an ordinal scale ranging from 0 to 4. Brain atrophy was measured semi-quantitatively on MRI. A binary logistic regression model was used to explore the association of SCH with each CSVD marker after adjusting for confounding factors. The ordinal regression model was used to explore the association of SCH with CSVD burden and brain atrophy after adjusting for confounding factors. RESULTS: The mean age of the participants (66.9% males) was 69.4±12.8 years. SCH was observed in 44 (12.4%) participants. MRI findings revealed 13% of cases with lacunes, 6.2% with microbleeds, 50.3% with confluent WMH, and 49.2% with extensive basal ganglia EPVS. Assessment of total CSVD burden showed that 29.1% scored 1, 30.5% scored 2, 6.5% scored 3, and 2.3% scored ≥3. SCH was associated with extensive basal ganglia EPVS [odds ratio (OR) =2.175; 95% confidence interval (CI): 1.075 to 4.401] and total CSVD load (OR =1.879; 95% CI: 1.028 to 3.438). SCH was not associated with advanced brain atrophy. CONCLUSIONS: SCH is associated with the advanced total burden of CSVD and basal ganglia EPVS in the stroke-free population.

Research progress of the POP fugacity model: a bibliometrics-based analysis.

With the emergence of environmental issues regarding persistent organic pollutants (POPs), fugacity models have been widely used in the concentration prediction and exposure assessment of POPs. Based on 778 relevant research articles published between 1979 and 2020 in the Web of Science Core Collection (WOSCC), the current research progress of the fugacity model on predicting the fate and transportation of POPs in the environment was analyzed by CiteSpace software. The results showed that the research subject has low interdisciplinarity, mainly involving environmental science and environmental engineering. The USA was the most paper-published country, followed by Canada and China. The publications of the Chinese Academy of Sciences, Lancaster University, and Environment Canada were leading. Collaboration between institutions was inactive and low intensity. Keyword co-occurrence analysis showed that polychlorinated biphenyls, organochlorine pesticides, and polycyclic aromatic hydrocarbons were the most concerning compounds, while air, water, soil, and sediment were the most concerning environmental media. Through co-citation cluster analysis, in addition to the in-depth exploration of traditional POPs, research on emerging POPs such as cyclic volatile methyl siloxane and dechlorane plus were new research frontiers. The distribution and transfer of POPs in the soil-air environment have attracted the most attention, and the regional grid model based on fugacity has been gradually improved and developed. The co-citation high-burst detection showed that the research hotspots gradually shifted from pollutant persistence and long-range transport potential to pollutant distribution rules among the different environmental media and the long-distance transmission simulation.

Cardiomyocytic FoxP3 is involved in Parkin-mediated mitophagy during cardiac remodeling and the regulatory role of triptolide.

Rationale: Forkhead/winged helix transcriptional factor P3 (FoxP3) is a well-studied transcription factor that maintains the activity of T cells, but whether cardiomyocytic FoxP3 participates in cardiac remodeling (CR) remains unclear. The present study was to investigate the role of cardiomyocytic FoxP3 in CR from the perspective of mitophagy. Methods: CR was induced by angiotensin II (AngII) in vitro, or by isoproterenol (Iso) in vivo using male C57 mice or FoxP3DTR mice. Histological changes were observed by hematoxylin-eosin and Masson staining. Molecular changes were detected by immunohistochemistry, immunofluorescence, immunoblotting, and real-time PCR. Mitophagy was shaped by transmission electron microscopy and co-localization. The mRNA expression was operated by siRNA or adeno associated virus (AAV). Molecular interactions were detected by co-localization, immunoprecipitation (IP), and chromatin IP. Results: The expression and nuclear translocation of cardiomyocytic FoxP3 were downregulated in CR, while they were upregulated after triptolide (TP) treatment. In left ventricle (LV) remodeling in mice, autophagy was activated continuously in the myocardium, and TP significantly attenuated it. AngII induced massive mitophagy characterized by the activation of autophagy regulatory protein 5 (Atg5)-dependent autophagic flux. Critically, Parkin was identified as the main adaptor mediated myocardial mitophagy and was responsible for the effect of TP. Moreover, FoxP3 was responsible for the downregulation of Parkin and inhibited AngII-induced cardiac mitophagy. We found that mitophagy increased significantly and the inhibition of TP treatment reversed completely in FoxP3-deficient LVs. Mechanistically, FoxP3 interacted with a motif located downstream of the activating transcription 4 (ATF4)-binding motif involved in the promoter of Parkin and hijacked free nuclear ATF4 to decrease Parkin mRNA expression in CR. Conclusion: Cardiomyocytic FoxP3 could negatively regulate Parkin-mediated mitophagy in CR, and restoring cardiomyocytic FoxP3 activity provided a cardioprotective strategy by inhibiting excessive cardiac mitophagy.

[To compare negative expiratory pressure technique with conventional tests in detecting expiratory flow limitation in chronic obstructive pulmonary diseases patients.].

OBJECTIVE: To compare negative expiratory pressure (NEP) technique with conventional test in detecting expiratory flow limitation (EFL) in chronic obstructive pulmonary diseases (COPD) patients. METHODS: EFL was measured with NEP technique and conventional method respectively in 72 COPD patients;EFL was measured with NEP technique in 20 COPD patients who failed to perform conventional test. RESULTS: EFL was detected in 54 of the 72 COPD patients. NEP test was successfully performed on the 20 patients, and 19 of them were found with EFL. The level of forced expired volume in one second percentage (FEV(1)%) of the patients with 2-score group (46.92 +/- 12.74)% and 3-score group (33.35 +/- 8.96)% were significantly lower than that of the 1-score group (63.60 +/- 16.65)%. Area under curve of NEP technique and conventional test in ROC is 0.903 and 0.761 respectively. CONCLUSIONS: As compared with conventional test, EFL detected with NEP technique is more reliable in evaluating dyspnea of COPD patients. It is simple and doesn't require any cooperation of the patients. NEP technique can be applied in COPD patients who fail to receive conventional test.

[Clinical Characteristics and Prognostic Significance of BCOR/BCORL1 Gene Mutation in Patients with Myelodysplastic Syndromes].

OBJECTIVE: To investigate the clinical characteristics and prognostic significance of myelodysplastic syndrome (MDS) patients with BCOR/BCORL1 mutation. METHODS: The clinical characteristics of 135 patients diagnosed as de novo MDS in People's Hospital of Xinjiang Uygur Autonomous Region from September 2015 to September 2019 were analyzed retrospectively. Next-generation sequencing was used to detect 34 kinds of myeloid-tumor-related gene in MDS patients. The clinical characteristics of BCOR/BCORL1 mutation and its effect to progression-free survival(PSF) and overall survival (OS) in MDS patients were analyzed. RESULTS: Among MDS patients, BCOR/BCORL1 mutation was found in 34(25.2%) patients, including 16(11.9%) BCOR mutation and 18(13.3%) BCORL1 mutation. Patients with BCOR/BCORL1 mutation were more common in women and showed lower neutrophil count ï¼»0.75(0.08-22.20) vs 1.27(0.06-35.71)×109/L, P=0.047ï¼½ as compared with those without BCOR/BCORL1 mutation. There were no significant difference in the rate of BCOR/BCORL1 mutation in different IPSS-R subgroups, the IPSS-R lower risk group and the IPSS-R higher risk group, different genetic groups, and conversion or non-conversion to leukemia group(P=0.725, P=0.713, P=0.273, P=0.165). BCOR/BCORL1 mutation was associated with DNMT3A, NF1, STAG2, U2AF1, and EZH2 mutation (P=0.003, P=0.007, P=0.000, P=0.004, P=0.024). While the median PFS of patients with BCOR/BCORL1 mutation showed no significantly different as compared with MDS patients without BCOR/BCORL1 mutation (P=0.210), but the median OS was significantly shorter ï¼»16(3-32) vs 22(0.2-48) months, P=0.039ï¼½. CONCLUSION: BCOR/BCORL1 mutation is more common in MDS patients and often company with other genes co-mutations. BCOR/BCORL1 mutation is not associated with disease progression and AML transformation in MDS patients, but it predicts poor overall survival.

Bama miniature pigs (Sus scrofa domestica) as a model for drug evaluation for humans: comparison of in vitro metabolism and in vivo pharmacokinetics of lovastatin.

The objective of this study was to demonstrate that Bama miniature pigs are a suitable experimental animal model for the evaluation of drugs for man. To this end, in vitro lovastatin metabolism at the minipig liver microsomal level and in vivo pharmacokinetics were studied. Results were compared with those obtained from humans. Our data indicate that the main metabolites and enzyme kinetic parameters of lovastatin metabolism are similar in pigs and humans. Triacetyloleandomycin, a specific inhibitor of human CYP3A4, inhibited the metabolism of lovastatin in pig and human liver microsomes. In addition, the pharmacokinetic parameters and absolute bioavailability suggested that the absorption and elimination of lovastatin in Bama miniature pigs were similar to those in humans. Lovastatin was distributed across many organs in pigs, but the highest levels were found in the stomach, intestines, and liver. Within 96 h, 7% and 82% of the given dose was excreted in the urine and feces, respectively. In addition, no significant species differences in the plasma protein binding ratio of lovastatin and the rates of lovastatin hydrolysis to beta-hydroxyacid lovastatin were apparent. From these results, we conclude that Bama miniature pigs are suitable for use in drug evaluation studies.

Current status and challenges of long-term safety evaluation of using tests of cosmetics on human body / 中华预防医学杂志

The use of cosmetics in the crowd has the long-term characteristics. The adverse reactions of cosmetics reported in other country in the world suggest that human patch tests and short-term human using test may not be sufficient to evaluate the safety of high-risk new cosmetic raw ingredients, and long-term human using test should be conducted for evaluation. Therefore, this article reviews the key factors that affect long-term human trial trials, such as site of use, single-use amount, frequency of use, duration of use, and subject conditions, providing supportive evidence for standardized safety evaluation standards for long-term human using test of cosmetics.

Current status and challenges of long-term safety evaluation of using tests of cosmetics on human body / 中华预防医学杂志

The use of cosmetics in the crowd has the long-term characteristics. The adverse reactions of cosmetics reported in other country in the world suggest that human patch tests and short-term human using test may not be sufficient to evaluate the safety of high-risk new cosmetic raw ingredients, and long-term human using test should be conducted for evaluation. Therefore, this article reviews the key factors that affect long-term human trial trials, such as site of use, single-use amount, frequency of use, duration of use, and subject conditions, providing supportive evidence for standardized safety evaluation standards for long-term human using test of cosmetics.

[Raman spectral study of nitrosyhemoglobin and several other hemoglobins].

The Raman spectra of nitrosyhemoglobin (NOHb), methemoglobin (MetHb), oxygenated hemoglobin (oxyHb), and deoxygenated hemoglobin(deoxyHb) were comparatively studied. The results show that the Raman spectra with 632.8 nm excitation can be used to detect the R state (oxyHb) to T state (deoxyHb) transition. The difference of NOHb and MetHb in their electron spin state was clearly demonstrated in their Raman spectra with 632.8 nm excitation, suggestingthat Raman spectra provide anew simple way to measure and distinguish NOHb and MetHb.

Response of aerobic granular sludge to the long-term presence to nanosilver in sequencing batch reactors: reactor performance, sludge property, microbial activity and community.

The increasing use of silver nanoparticles (Ag NPs) raises concerns about their potential toxic effects on the environment. Granular shape sludge is a special type of microbial aggregate. The response of aerobic granular sludge (AGS) to the long-term presence of Ag NPs has not been well studied. In this study, AGS was exposed to 5 and 50mg/L Ag NPs in sequence batch reactors (SBRs) for 69 days, and its response was evaluated based on the sludge properties, microbial activity and community, and reactor performance. The results showed that Ag NPs caused inhibition to microbial activities of AGS from Day 35. At the end of 69 days of Ag NPs exposure, the microbial activity of AGS was significantly inhibited in terms of inhibitions of the ammonia oxidizing rate (33.0%), respiration rate (17.7% and 45.6%) and denitrification rate (6.8%), as well as decreases in the ammonia mono-oxygenase and nitrate reductase activities. During the long-term exposure, the AGS maintained its granular shape and large granule size (approximately 900 µm); the microbial community of AGS slightly changed, but the dominant microbial population remained. Overall, the AGS tolerated the toxicity of Ag NPs well, but a long-term exposure may produce chronic toxicity to the AGS, which is concerning.

Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma.

The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics.

The activation state of Rubisco directly limits photosynthesis at low CO(2) and low O(2) partial pressures.

Using gas exchange, enzyme assays, and theoretical modeling of photosynthetic responses to light and CO(2), we investigated whether decarbamylation of the active site of Rubisco at low CO(2) and low light leads to a condition where the activation state of Rubisco directly limits the rate of net CO(2) assimilation. Photosynthetic limitation by a reduction in the activation state of Rubisco would be indicated as a decline in the initial slope of the photosynthetic CO(2) response relative to what is predicted using theoretical models. In bean (Phaseolus vulgaris) and oat (Avena sativa), we saw no discrepancy between predicted and observed initial slope values at 200 and 400 mbar O(2), indicating no limitation by the carbamylation state of Rubisco. At 30 mbar O(2) and light saturation, we also saw no discrepancy between predicted and observed initial slope values; however, at subsaturating light intensity, our observed initial slope values were less than the modeled initial slope values that corresponded to an RuBP regeneration limitation. Moreover, significant reduction of the Rubisco activation state occurred in both species at 30 mbar O(2) and 30 mubar CO(2). When the model was reprogrammed to account for observed levels of Rubisco deactivation, the predicted and measured initial slope values at low O(2) and low PPFD were similar, indicating the reduction in carbamylation state accounted for the discrepancy. We interpret this as evidence for a direct limitation of the carbamylation state of Rubisco, probably because of a CO(2) limitation for carbamate formation. This limitation was only observed at intercellular CO(2) levels below what is encountered in vivo. At physiologically relevant CO(2) levels in situ, the leaves maintained sufficient Rubisco activity to avoid cabamylation state limitations in the steady state.