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Purpose: To investigate the safety and effectiveness of semen strychni total alkaloid microcapsules (SSTAM), compared with semen strychni total alkaloids (SSTA). Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to assess pharmacokinetics of brucine and strychnine in rats. Acute toxicity was investigated in pre-test and formal experiments in mice. The pharmacodynamics of SSTAM and SSTA were evaluated by their analgesic and anti-inflammatory activities. Results: With respect to brucine, the half-life of SSTA group (1.6 mg/kg), low-dose SSTAM group (6 mg/kg) and high-dose SSTAM group (10 mg/kg) was 5.723, 9.321 and 9.025 h, respectively. With respect to strychnine, the half-life of SSTA group, low-dose SSTAM group and high-dose SSTAM group was 4.065, 8.819 and 8.654 h, respectively. The LD50 values of SSTAM group and SSTA group were 236.59 and 30.27 mg/kg, respectively. The pain inhibition rates of SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group (p < 0.05) while the pain threshold values of the SSTAM groups (25 and 50 mg/kg) were higher than that of blank control (p < 0.01) and SSTA groups (p < 0.01) at 60 min and 120 min. The inhibition rates of the SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group based on ear swelling and cotton ball granulation tests. Compared with blank control and SSTA groups, the absorbance values of SSTAM groups (25 and 50 mg/kg) were lower (p < 0.01). Conclusion: SSTAM increases the dosage of administration but reducea the toxicity of the alkaloids in rats, and is thus a potentially safe and effective drug delivery system. [ABSTRACT FROM AUTHOR]

Abstract Accurate and efficient detection of pathogenic bacteria plays a crucial role in the diagnosis of infectious diseases. However, rapid and highly sensitive detection of specific bacteria in clinical samples remains challenging. In this study, we developed a ratiometric dual‐signal electrochemical biosensor for ultrasensitive detection of pathogenic bacteria, based on an aptamer recognition‐induced rolling circle amplification (RCA)/G‐quadruplex strategy. On the surface of a gold electrode chip, we used an aptamer sequence (P1) conjugated to ferrocene (Fc) to capture the target bacterium. This capture released a different, previously bound sequence (P2) sequence that initiated the RCA/G‐quadruplex cascade, which, in the presence of potassium ions, was able to bind the electrochemical indicator methylene blue (MB). We integrated the signals from the loss of Fc and the appearance of MB (IMB/IFC ratio) to quantify the target bacteria concentration. This biosensor showed excellent detection performance and specificity, with a detection limit of 10 CFU/mL. Notably, it showed great diagnostic potential for clinical infectious diseases caused by pathogenic bacteria in precise/personalized medicine applications.

BACKGROUND: Otoconia-related vertigo and balance deficits are common in humans, but the molecular etiology is unknown at present. OBJECTIVE: In order to study mechanisms of otoconia formation and maintenance, we have investigated whether otoconin-90 (Oc90), the predominant otoconial constituent protein, and the NADPH oxidase Nox3, an essential regulatory protein for otoconia formation, are functionally interlinked. METHODS: We performed balance behavioral, electrophysiological, morphological and molecular cellular analyses. RESULTS: Double heterozygous mutant mice for Oc90 and Nox3 show severe imbalance, albeit less profound than double null mutants. In contrast, single heterozygous mutant mice have normal balance. Double heterozygous mice have otoconia defects and double null mice have no otoconia. In addition, some hair bundles in the latter mice go through accelerated degeneration. In vitro calcification analysis in cells stably expressing these proteins singly and doubly shows much more intense calcification in the double transfectants. CONCLUSIONS: Oc90 and Nox3 augment each other's function, which is not only critical for otoconia formation but also for hair bundle maintenance. [ABSTRACT FROM AUTHOR]

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in humans, yet the molecular etiology is currently unknown. Evidence suggests that genetic factors may play an important role in some cases of idiopathic BPPV, particularly in familial cases, but the responsible genetic variants have not been identified. In this study, we performed whole exome sequencing [including untranslated regions (UTRs)] of 12 families and Sanger sequencing of additional 30 families with recurrent BPPV in Caucasians from the United States (US) Midwest region, to identify the genetic variants responsible for heightened susceptibility to BPPV. Fifty non-BPPV families were included as controls. In silico and experimental analyses of candidate variants show that an insertion variant rs113784532 (frameshift causing truncation) in the neural cadherin gene PCDHGA10 (protocadherin-gamma A10) is an exceedingly strong candidate (p = 1.80x10-4 vs. sample controls; p = 5.85x10-19 vs. ExAC data; p = 4.9x10-3 vs. NHLBI exome data). The mutant protein forms large aggregates in BPPV samples even at young ages, and affected subjects carrying this variant have an earlier onset of the condition than those without [average 44.0±14.0 (n = 16) versus 54.4±16.1 (n = 36) years old, p = 0.054]. In both human and mouse inner ear tissues, PCDHGA10 is expressed in ganglia, hair cells and vestibular transitional epithelia. Fluorescent RNA in situ hybridization using mouse inner ear tissues shows that expression increases with age. In summary, our data show that a variant in the PCDHGA10 gene may be involved in causing or aggravating some familial cases of recurrent idiopathic BPPV. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the anti-cancer effects of bufalin against the human gastric cancer cells and unveil the underlying mechanism. The results showed that bufalin inhibited the proliferation and colony formation of the MGC-803 gastric cancer cells and exhibited an IC50 of 10 μM. These antiproliferative effects were found to be due to the induction of G2/M cell cycle arrest. The G2/M cell cycle arrest was also concomitant with inhibition of cdc2, cdc25 and cyclin B1. Furthermore, bufalin suppressed the epithelial-to -mesenchymal transition, migration, and invasion of the MGC-803 gastric cancer cells. The Western blot analysis revealed that bufalin exerted its effects via deactivation of EK/ERK signaling pathway. Taken together, these results suggest the potential of bufalin as the lead molecule for the development of chemotherapy for gastric cancer. [ABSTRACT FROM AUTHOR]

The article presents a study on three-dimensional DNA tweezers (TD-DNA tweezers) serve as modular DNA intelligent machines for detection and regulation of intracellular microRNA. Topics discussed include TD-tweezers have been tested in whole blood, preliminarily verifying their clinical application potential; design provides a multifunctional platform that can achieve efficient detection and regulation of targets within living cells and promote the development of DNA intelligent machines.

Aiming at improving the seed spacing uniformity of maize planter at high forward speed, a seed precise delivery mechanism driven by electric motor has been developed and evaluated in laboratory. The mechanism was designed to deliver single seed from seed meter to furrow. Seed's movement from the seed release point in a seed meter to the seed delivery cavity in the belt was analyzed, the mathematical model of seed movement in the seed precise delivery mechanism was established based on seed delivery time analysis. A mechanical prototype was designed and associated control system was developed. The performance contrast experiment was conducted between a traditional seed tube and newly developed seed precise delivery mechanism, and test results indicated that the qualities of feed index of the seed precise delivery mechanism were higher than those of the traditional seed tube delivery mechanism, and the coefficients of variation of the seed precise delivery mechanism were lower than those of the traditional seed tube delivery mechanism when the forward speed of planter was set at 10 km/h, 12 km/h and 14 km/h, respectively. It indicated the seed precise delivery mechanism significantly improved seed spacing uniformity of maize planter compared with the traditional seed tube delivery mechanism. [ABSTRACT FROM AUTHOR]

The quantitative structure property relationship (QSPR) for the gas/particle partition coefficient, Kp, of polychlorinated biphenyls (PCBs) was investigated. Molecular distance-edge vector (MDEV) index was used as the structural descriptor of the PCBs. The quantitative relationship between the MDEV index and log Kp was modeled by multivariate linear regression (MLR) and artificial neural network (ANN), respectively. The leave-one-out cross validation and external validation were performed to assess the prediction ability of the developed models. When the MLR method was used, the root mean square relative error (RMSRE) of the prediction for the leave-one-out cross validation and external validation were 4.72 and 8.62, respectively. When the ANN method was employed, the prediction RMSRE of the leave-one-out cross validation and the external validation were 3.87 and 7.47, respectively. It was demonstrated that the developed models are practicable for predicting the Kp of PCBs. The MDEV index was shown to be quantitatively related to the Kp of PCBs. [ABSTRACT FROM AUTHOR]

Abstract: Hybrid indica rice (Oryza sativa L.) cultivars play an important role in rice production system due to its heterosis, resistance to environmental stress, large panicle and high yield potential. However, no attention has been given to its yield responses to rising atmospheric [CO2] in conjunction with nitrogen (N) availability. Therefore we conducted a free air CO2 enrichment (FACE) experiment at Yangzhou, Jiangsu, China (119°42′0′′E, 32°35′5′′N), in 2004–2006. A three-line hybrid indica rice cv. Shanyou 63 was grown at ambient and elevated (ca. 570μmolmol−1) [CO2] under two levels of supplemental N (12.5gNm−2 and 25gNm−2). Elevated [CO2] had no effect on phenology, but substantially enhanced grain yield (+34%). The magnitude of yield response to [CO2] was independent of N fertilization, but varied among different years. On average, elevated [CO2] increased the panicle number per square meter by 10%, due to an increase in maximum tiller number under enrich [CO2], while productive tiller ratio remained unaffected. Spikelet number per panicle also showed an average increase of 10% due to elevated [CO2], which was supported by increased plant height and stem dry weight per tiller. Meanwhile, elevated [CO2] caused a significant enhancement in both filled spikelet percentage (+5%) and individual grain weight (+4%). Compared with the two prior FACE studies on rice, hybrid indica rice cultivar appears to profit much more from elevated [CO2] than japonica rice cultivar (ca. +13%), not only due to its stronger sink generation, but also enhanced capacity to utilize the carbon sources in a high [CO2] environment. The above data has significant implication with respect to N strategies and cultivar selection under projected future [CO2] levels. [Copyright &y& Elsevier]

The syntheses of several new simple negative, a simple positive, and multiple negative photochromes containing the dihydropyrene-cyclophanediene photochromic system are described. The photo-openings of the negative photochromes, the [e]-annelated benzo (7), naphtho (9), anthro (11), furano (19), and triphenyleno (15) derivatives of the parent 2,7-di-tert-butyl-trans-10b, 10c-dimethyl-dihydropyrene (5), as well as its 4,5-dibromo derivative (13), are described to give the corresponding cyctophanedienes, as well as their photoclosures and thermal closures back to the dihydropyrenes. These are compared to the results obtained for the positive photochrome dibenzo[e,l]dihydropyrene (21) and to the bis(dihydropyreno)chrysene (44) and the (dihydropyrenobenzo)(benzo)metacyclophanediene (47) photochromes, which have more than one photochromic switch present and thus have more than a simple "on off" state. Thermodynamic data are obtained for the thermal closing reactions. The anthrodihydropyrene (12) has the fastest thermal closing (τ[sub ½] = 20 min), while the furanodihydropyrene (19') has the slowest (τ[sub ½] = 63 h) at 46 °C. An electrochemical readout of the state of the switch is demonstrated for the benzodihydropyrene (7). [ABSTRACT FROM AUTHOR]

We investigate the extent and nature of productivity growth in Sub-Saharan African countries using non-parametric frontier techniques. In this work, we examine agricultural total factor productivity (TFP) change in 44 countries in Sub-Saharan Africa (SSA), covering a period of fifty-nine (59) years (1961-2019). We make use of data drawn from the Food and Agriculture Organization of the United Nations. Due to the non-availability of reliable input price data, the study uses data envelopment analysis (DEA) to derive Malmquist productivity indices. The results demonstrate a decline in agricultural TFP growth in the region from 1961 to 2019. This notwithstanding, a general average growth was seen in some of the conventional inputs measured (land, labour, capital, and fertilizer) which are the main drivers of growth in the region. This finding implies that the increase in agricultural output over the past five decades in SSA is mainly due to an increased use of conventional inputs over time, including land, and not due to an increase in the ratio of output over inputs. As a generally acceptable and preferred indicator of technical and efficiency changes, we use TFP to calculate the Malmquist productivity index (MPI)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Baion et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In this review the authors discuss evidence from the literature concerning vitamin D and temporal bone diseases (benign paroxysmal positional vertigo [BPPV], Menière's disease [MD], vestibular neuritis, idiopathic facial paralysis, idiopathic acute hearing loss). Common features shared by Menière's disease, glaucoma, and the possible influence by vitamin D are briefly discussed., Data Sources, Study Selection: Publications from 1970 until recent times have been reviewed according to a keyword search (see above) in PubMed., Conclusions: MD, BPPV, vestibular neuritis, idiopathic facial paralysis, idiopathic acute hearing loss may all have several etiological factors, but a common feature of the current theories is that an initial viral infection and a subsequent autoimmune/autoinflammatory reaction might be involved. Additionally, in some of these entities varying degrees of demyelination have been documented. Given the immunomodulatory effect of vitamin D, we postulate that it may play a role in suppressing an eventual postviral autoimmune reaction. This beneficial effect may be enhanced by the antioxidative activity of vitamin D and its potential in stabilizing endothelial cells. The association of vitamin D deficiency with demyelination has already been established in other entities such as multiple sclerosis and experimental autoimmune encephalitis. Mice without vitamin D receptor show degenerative features in inner ear ganglia, hair cells, as well as otoconia. The authors suggest further studies concerning the role of vitamin D deficiency in diseases of the temporal bone. Additionally, the possible presence and degree of demyelination in these entities will have to be elucidated more systematically in the future.

Objectives: Costimulatory molecules are increasingly recognized as crucial for stimulation and/ or inhibition of immune responses. The present study was undertaken to examine the expression and functional relevance of B7-homolog 1 (B7-H1) attributed significant immunoregulatory functions in polymyositis in vivo., Methods: 43 muscle biopsy specimens obtained from patients with polymyositis, 26 cases with limb girdle muscular dystrophies (LGMD) 2B and 21 normal muscle samples were analyzed by immunohistochemistry for B7-H1 expression. The clinical and histopathologic data were analyzed., Results: B7-H1 was not detectable on normal muscle fibers and rarely detectable from patients with LGMD-2B. In contrast, its expression was markedly increased on muscle fibers from patients with polymyositis, even after short-term immunosuppressive treatment. Positive staining mainly localized at the surface of the muscle tissue, rarely in the cytoplasm, focused in areas where inflammatory cells lay in close apposition to damaged, necrotic or degenerative muscle fibers. The expression of B7-H1 was correlated to the degrees of muscular necrosis and clinical muscular strength., Conclusion: Our results demonstrate that human muscle cells express B7-H1 in polymyositis. The muscle-related expression of B7-H1 may be helpful in the diagnosis of polymyositis and might be an indicator of prognosis of polymyositis.

Human neural tube defects (NTDs) are among the most common congenital defects. They have a highly heterogeneous etiology, and, in addition to those seen in association with genetic syndromes, there are also NTDs induced by pharmaceutical compounds in utero, such as the widely used anti-epileptic drug valproic acid (VPA). Although familial studies have suggested a genetic contribution to VPA-induced NTDs, this trait has not been adequately studied, nor have the responsible genetic factors been identified. We generated a series of mouse crosses and backcrosses using the highly inbred SWV/Fnn and C57BL/6J strains, in order to identify possible chromosomal loci contributing to VPA sensitivity. When exposed to a high dose of sodium VPA (600 mg/kg) via maternal intraperitoneal injection on gestational day E8.5, the fetuses manifested exencephaly in a strain-dependent manner. Our data show an autosomal recessive trait, plus a gender-related effect or an overall X-Chromosome (Chr) effect, as being primarily responsible for determining sensitivity to VPA-induced exencephaly. Genome scanning and further linkage analysis of 131 exencephalic backcross fetuses identified a major locus linked to D7Mit285 (p < 2 x 10(-6)), exceeding the threshold for significant linkage. These results suggest a major chromosomal locus associated with the sensitivity to VPA-induced exencephaly in mice.