The polymethoxylated flavone hexamethylquercetagetin suppresses NF-κB signaling and inhibits cell survival in cervical carcinoma.

Nuclear factor-κB (NF-κB) contributes to the development and progression of cervical carcinoma. To construct a xenograft model, Ca Ski cells were subcutaneously inoculated into BALB/c nude mice. The relative protein expression of NF-κB p65, p-p65, IκBα, and p-IκBα were detected in hexamethylquercetagetin (HTQC) treated cervical carcinoma cells with or without tumor necrosis factor (TNF)α stimulation, or representative tumors tissues in xenograft mice. HTQC could prohibit NF-κB-derived luciferase activity in Ca Ski and C-33 A cells and inhibit the relative NF-κB p-p65 and p-IκBα expression with or without TNFα stimulation. At the same time, HTQC inhibited in vitro cell survival in a concentration-dependent manner and suppressed the tumor volume and weight in xenograft models. In summary, HTQC functions as an NF-κB inhibitor to prohibit the survival and proliferation of cervical carcinoma, which can be considered as an NF-κB target remedy in future clinical practice.

Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice.

High altitude cerebral edema (HACE) is a life-threatening illness that develops during the rapid ascent to high altitudes, but its underlying mechanisms remain unclear. Growing evidence has implicated inflammation in the susceptibility to and development of brain edema. In the present study, we investigated the inflammatory response and its roles in HACE in mice following high altitude hypoxic injury. We report that acute hypobaric hypoxia induced a slight inflammatory response or brain edema within 24h in mice. However, the lipopolysaccharide (LPS)-induced systemic inflammatory response rapidly aggravated brain edema upon acute hypobaric hypoxia exposure by disrupting blood-brain barrier integrity and activating microglia, increasing water permeability via the accumulation of aquaporin-4 (AQP4), and eventually leading to impaired cognitive and motor function. These findings demonstrate that hypoxia augments LPS-induced inflammation and induces the occurrence and development of cerebral edema in mice at high altitude. Here, we provide new information on the impact of systemic inflammation on the susceptibility to and outcomes of HACE.

Unraveling the causal association between leukocyte telomere length and infertility: A two-sample Mendelian randomization study.

Infertility is a significant challenge in modern society, and observed studies have reported the association between telomere length and infertility. Whether this relationship is causal remains controversial.We employed two-sample mendelian randomization (MR) to investigate the causal relationship between leukocyte telomere length (LTL) and major causes of infertility, including male and female infertility, sperm abnormalities, and endometriosis. MR analyses were mainly performed using the inverse variance weighted (IVW) method and complemented with other MR methods.Our findings demonstrate a causal association between LTL and endometriosis (OR1.304, 95% CI (1.122,1.517), p = 0.001), suggesting its potential as a biomarker for this condition. However, we did not observe a significant causal relationship between LTL and other infertility causes.Our study presents compelling evidence on the relationship between LTL and endometriosis. Meanwhile, our study demonstrates that there is no causal relationship between LTL and infertility. This research contributes to the field by shedding light on the importance of LTL in the early diagnosis and intervention of endometriosis.

Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

Population coding for figure-ground texture segregation in macaque V1 and V4.

Object recognition often involves the brain segregating objects from their surroundings. Neurophysiological studies of figure-ground texture segregation have yielded inconsistent results, particularly on whether V1 neurons can perform figure-ground texture segregation or just detect texture borders. To address this issue from a population perspective, we utilized two-photon calcium imaging to simultaneously record the responses of large samples of V1 and V4 neurons to figure-ground texture stimuli in awake, fixating macaques. The average response changes indicate that V1 neurons mainly detect texture borders, while V4 neurons are involved in figure-ground segregation. However, population analysis (SVM decoding of PCA-transformed neuronal responses) reveal that V1 neurons not only detect figure-ground borders, but also contribute to figure-ground texture segregation, although requiring substantially more principal components than V4 neurons to reach a 75 % decoding accuracy. Individually, V1/V4 neurons showing larger (negative/positive) figure-ground response differences contribute more to figure-ground segregation. But for V1 neurons, the contribution becomes significant only when many principal components are considered. We conclude that V1 neurons participate in figure-ground segregation primarily by defining the figure borders, and the poorly structured figure-ground information V1 neurons carry could be further utilized by V4 neurons to accomplish figure-ground segregation.

TBX3 promotes the epithelial mesenchymal transition of cervical cancer by upregulating ID1.

In this study, we aim to investigate the role and mechanism of T-box transcription factor 3 (TBX3) in cervical cancer. The mRNA and protein expression of TBX3, inhibitor of DNA binding 1 (ID1), and epithelial mesenchymal transition (EMT) markers (E-Cadherin, N-Cadherin, and vimentin) were measured using qRT-PCR and Western blot. shTBX3 and shID1 were transfected into SiHa cells to knockdown TBX3 and ID1. The metastasis and invasion abilities of cervical cancer cells were determined using a wound healing assay and an invasive assay. The shTBX3- and shID1-transfected SiHa cells were injected into nude mice using a xenograft tumor growth model. We found that TBX3 and ID1 were highly expressed in cervical cancer cells. Importantly, silencing TBX3 and ID1 significantly reduced the migration and metastasis of cervical cancer cells. In addition, silencing TBX3 and ID1 significantly inhibited the EMT, evidenced by the increased E-cadherin, and decreased N-cadherin and vimentin. The size and weight of the xenograft tumor were significantly reduced by shTBX3 and shID1. We demonstrate that TBX3 or ID1 knockdown can effectively inhibit cervical cancer cells migration and invasion. These findings indicate that TBX3 and ID1 can act as potential therapeutic targets for the prevention and treatment of cervical cancer.

Intermittent hypoxia treatment alleviates memory impairment in the 6-month-old APPswe/PS1dE9 mice and reduces amyloid beta accumulation and inflammation in the brain.

BACKGROUND: Alzheimer's disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. METHODS: Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aß) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. RESULTS: IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aß plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1ß, IL-6 levels, and ß-secretase cleavage of APP processing which implies reduced Aß production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. CONCLUSIONS: This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aß accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

Perceptual learning of motion direction discrimination: Location specificity and the uncertain roles of dorsal and ventral areas.

One interesting observation of perceptual learning is the asymmetric transfer between stimuli at different external noise levels: learning at zero/low noise can transfer significantly to the same stimulus at high noise, but not vice versa. The mechanisms underlying this asymmetric transfer have been investigated by psychophysical, neurophysiological, brain imaging, and computational modeling studies. One study (PNAS 113 (2016) 5724-5729) reported that rTMS stimulations of dorsal and ventral areas impair motion direction discrimination of moving dot stimuli at 40% coherent ("noisy") and 100% coherent (zero-noise) levels, respectively. However, after direction training at 100% coherence, only rTMS stimulation of the ventral cortex is effective, disturbing direction discrimination at both coherence levels. These results were interpreted as learning-induced changes of functional specializations of visual areas. We have concerns with the behavioral data of this study. First, contrary to the report of highly location-specific motion direction learning, our replicating experiment showed substantial learning transfer (e.g., transfer/learning ratio = 81.9%. vs 14.8% at 100% coherence). Second and more importantly, we found complete transfer of direction learning from 40% to 100% coherence, a critical baseline that is missing in this study. The transfer effect suggests that similar brain mechanisms underlie motion direction processing at two coherence levels. Therefore, this study's conclusions regarding the roles of dorsal and ventral areas in motion direction processing at two coherence levels, as well as the effects of perceptual learning, are not supported by proper experimental evidence. It remains unexplained why distinct impacts of dorsal and ventral rTMS stimulations on motion direction discrimination were observed.

Seismic Behavior of Superelastic Shape Memory Alloy Spring in Base Isolation System of Multi-Story Steel Frame.

Owing to excellent re-centering capability and good damping behavior, superelastic shape memory alloys (SMAs) are emerging as a potential new material to enhance the seismic resilience of civil structures. This paper focuses on using base isolation with SMA device for isolated structures. SMA springs are deemed to be promising candidate as the damper in the base isolation system, due to the compact form, damping contribution, restoring capability and flexible stiffness. This paper reported the concept of an innovative spring which is made of superelastic SMA wire. Then cyclic loading tests were carried out to evaluate the interested cyclic properties. Parametric analyses based on finite element simulations were conducted to reveal the versatile performance of SMA springs. To further examine its seismic behavior in the base isolation system, the SMA spring was later installed at the isolation level of a multi-story steel frame, based on the finite element model built in the earthquake engineering simulation platform OpenSees. An ordinary elastic spring is included for comparison to highlight the features of SMA springs. Both isolated frames were subjected to real earthquakes. The comparisons indicated that using SMA spring is more effective in controlling maximum and residual deformation for the protected superstructures. Thus, this paper well demonstrated the feasibility and merits of using SMA springs in the isolated frames.

Effects of tidal action on pollination and reproductive allocation in an estuarine emergent wetland plant-Sagittaria graminea (Alismataceae).

In estuarine wetlands, the daily periodic tidal activity has a profound effect on plant growth and reproduction. We studied the effects of tidal action on pollination and reproductive allocation of Sagittaria graminea. Results showed that the species had very different reproductive allocation in tidal and non-tidal habitats. In the tidal area, seed production was only 9.7% of that in non-tidal habitat, however, plants produced more male flowers and nearly twice the corms compared to those in non-tidal habitat. An experiment showed that the time available for effective pollination determined the pollination rate and pollen deposition in the tidal area. A control experiment suggested that low pollen deposition from low visitation frequency is not the main cause of very low seed sets or seed production in this plant in tidal habitat. The negative effects of tides (water) on pollen germination may surpass the influence of low pollen deposition from low visitation frequency. The length of time from pollen deposition to flower being submerged by water affected pollen germination rate on stigmas; more than three hours is necessary to allow pollen germination and complete fertilization to eliminate the risk of pollen grains being washed away by tidal water.