Efficient photoactivatable Dre recombinase for cell type-specific spatiotemporal control of genome engineering in the mouse.

Precise genetic engineering in specific cell types within an intact organism is intriguing yet challenging, especially in a spatiotemporal manner without the interference caused by chemical inducers. Here we engineered a photoactivatable Dre recombinase based on the identification of an optimal split site and demonstrated that it efficiently regulated transgene expression in mouse tissues spatiotemporally upon blue light illumination. Moreover, through a double-floxed inverted open reading frame strategy, we developed a Cre-activated light-inducible Dre (CALID) system. Taking advantage of well-defined cell-type-specific promoters or a well-established Cre transgenic mouse strain, we demonstrated that the CALID system was able to activate endogenous reporter expression for either bulk or sparse labeling of CaMKIIα-positive excitatory neurons and parvalbumin interneurons in the brain. This flexible and tunable system could be a powerful tool for the dissection and modulation of developmental and genetic complexity in a wide range of biological systems.

Urban-rural disparities in hypertension prevalence, awareness, treatment, and control among Chinese middle-aged and older adults from 2011 to 2015: a repeated cross-sectional study.

BACKGROUND: China has experienced a continuing increase in hypertension prevalence over the past few decades, especially in rural areas. The paper aims to examine the variation of urban-rural disparities in hypertension prevalence, awareness, treatment, and control among Chinese middle-aged and older adults between 2011 and 2015. METHODS: Our team extracted data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of residents aged 45 years and older. In this study, we used the 2011 wave and the 2015 wave of CHARLS. We calculated crude rates and age-adjusted rates of hypertension prevalence, awareness, treatment, and control for the general, urban, and rural populations in each wave and performed chi-square tests to examine urban-rural disparities. We used logistic regression to further confirm these disparities by controlling confounding factors in each wave. We then used generalized estimating equation (GEE) to further examine whether urban-rural disparities changed between 2011 and 2015. RESULTS: We included 11,129 records in the 2011 wave and 8916 records in the 2015 wave in this study. The mean age was 59.0 years and 5359 (48.2%) participants were male in the 2011 wave. Age-adjusted hypertension prevalence, awareness, treatment, control, and control among treated in the total population were 38.5%, 70.6%, 59.2%, 27.4%, and 46.4% in 2015. Urban-rural disparities in the indicators mentioned above were 5.7%, 13.4%, 15.3%, 9.4% and 5.6% in 2011; which decreased to 4.8%, 2.7%, 5.2%, 4.9% and 3.8% in 2015. Urban-rural disparities in prevalence, awareness and treatment were statistically significant in 2011 but not significant in 2015 adjusted for confounding factors, yet control disparities were statistically significant in both waves. Finally, urban-rural disparities in awareness and treatment had narrowed from 2011 to 2015. CONCLUSIONS: Awareness, treatment, and control rates were sub-optimal among both urban and rural adults. Prevention and management of hypertension among both urban and rural adults should be further strengthened. Awareness and treatment increased more rapidly among rural adults, indicating some achievement had been made in enhancing the healthcare system in rural areas. More efforts are needed in attaining urban-rural equity of healthcare services.

Positive and neutral updating reconsolidate aversive episodic memories via different routes.

Aversive memories are long-lasting and prone to burden our emotional wellbeing and mental health. Yet, how to remedy the maladaptive effects of aversive memories remains elusive. Using memory reactivation and emotional updating manipulations, we investigated how positive and neutral emotion may update aversive memories for reconsolidation in humans. We found that positive updating after reactivation was equivalent to neutral updating in impairing true memories of a previous aversive event after a 12-hour wakeful delay, but induced more false memory. Moreover, additional 12-hour delay with overnight sleep did not further enlarge true memory differences, but attenuated the effect of reactivation and updating on false memory. Interestingly, the neutral rather than the positive updating reduced the emotional arousal of the aversive memory 24 h later. Our findings could serve as a reference for real-world therapeutic applications regarding how positive and neutral updating may reshape aversive memories, especially when taking wake- and sleep-filled reconsolidation into account.

A brainstem-central amygdala circuit underlies defensive responses to learned threats.

Norepinephrine (NE) plays a central role in the acquisition of aversive learning via actions in the lateral nucleus of the amygdala (LA) [1, 2]. However, the function of NE in expression of aversively-conditioned responses has not been established. Given the role of the central nucleus of the amygdala (CeA) in the expression of such behaviors [3-5], and the presence of NE axons projections in this brain nucleus [6], we assessed the effects of NE activity in the CeA on behavioral expression using receptor-specific pharmacology and cell- and projection-specific chemogenetic manipulations. We found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively. We then show that locally inhibiting or activating LC terminals in CeA is sufficient to achieve this bidirectional modulation of defensive reactions. These findings support the hypothesis that LC projections to CeA are critical for the expression of defensive responses elicited by conditioned threats.

Comparative proteomics analysis of spermary and ovary in Hyriopsis schlegelii.

We provide the first large-scale quantitative proteomics analysis in Hyriopsis schlegelii. To investigate the proteins expressed in the gonads, a quantitative proteomics approach has been utilized to analyze differentially expressed proteins between the spermary and ovary. In this study, we identified and quantified 2416 proteins in the gonads of Hyriopsis schlegelii. Of these, 559 proteins showed significantly different expression between the spermary and ovary. Some specific proteins expressed in either the spermary or ovary were identified in Hyriopsis schlegelii. In addition, a series of proteins related to gametogenesis were also identified. Compared with previous reports, many proteins in Hyriopsis schlegelii identified here have different expression patterns between the spermary and ovary. The special hermaphroditism in Hyriopsis schlegelii may contribute to these inconsistent results. The provided proteomics data could be considered as a starting point for subsequent studies focusing on the proteins involved in sexual gland development and maturity.

Dynamic light manipulation via silicon-organic slot metasurfaces.

Active metasurfaces provide the opportunity for fast spatio-temporal control of light. Among various tuning methods, organic electro-optic materials provide some unique advantages due to their fast speed and large nonlinearity, along with the possibility of using fabrication techniques based on infiltration. In this letter, we report a silicon-organic platform where organic electro-optic material is infiltrated into the narrow gaps of slot-mode metasurfaces with high quality factors. The mode confinement into the slot enables the placement of metallic electrodes in close proximity, thus enabling tunability at lower voltages. We demonstrate the maximum tuning sensitivity of 0.16nm/V, the maximum extinction ratio of 38% within ± 17V voltage at telecommunication wavelength. The device has 3dB bandwidth of 3MHz. These results provide a path towards tunable silicon-organic hybrid metasurfaces at CMOS-level voltages.

A non-image-forming visual circuit mediates the innate fear of heights in male mice.

The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.

JARID2 regulates epithelial mesenchymal transition through the PTEN/AKT signalling pathways in ovarian endometriosis.

Recently, it has been proposed that epithelial-mesenchymal transition (EMT) plays a key role in the development of endometriosis (EMs). Although EMs is a benign disease, it has the characteristics of malignant tumors, such as invasion and migration. JARID2 (Jumonji, AT rich interaction domain) can induce EMT in cancer cells to increase their invasion and migration abilities. However, whether JARID2 has the same function in EMs is not yet known. In this study, A retrospective immunohistochemistry(IHC) was used to measure the expression of JARID2, E-cadherin, PTEN, and p-AKT in ovarian endometriosis (OE) tissues. JARID2, EMT and PTEN/AKT signaling pathway related indicators were assessed by RT-PCR and western blotting in vitro. Furthermore, functional assays were applied to evaluate the involvement of JARID2 in the invasion and migration of Ishikawa cells. Here,we conclude that JARID2 could be involved in the PTEN/AKT signalling pathway and contribute to the development of ovarian endometriosis. The expression of JARID2 was negatively correlated with PTEN, but positively correlated with p-AKT in the ectopic endometrial tissues of OE cases. JARID2 overexpression increased the expression of N-cadherin, vimentin and AKT, but inhibited the expression of E-cadherin and PTEN. Accordingly, the opposite results were obtainedwhen JARID2 was downregulated. Furthermore, JARID2 promoted the invasion and migration ability of Ishikawa cells.

Prevalence of self-reported chronic conditions and poor health among older adults with and without vision impairment in China: a nationally representative cross-sectional survey.

OBJECTIVE: To examine the self-reported prevalence of 13 chronic conditions and poor health among Chinese adults aged 45 years and older with and without self-reported vision impairment. DESIGN: Cross-sectional study from the China Health and Retirement Longitudinal Study 2018, a nationally representative survey of Chinese adults aged 45 years and older involving 19 374 participants. METHODS: We used logistic regression to assess the association between vision impairment and 13 common chronic conditions and between vision impairment and poor health for those with any of these chronic conditions. RESULTS: Older people with self-reported vision impairment were significantly more likely to report all 13 chronic conditions (all p<0·05). After controlling for age, gender, education, residential status (rural vs urban), smoking and BMI, the highest adjusted odds were for hearing impairment (OR=4.00 (95% CI 3·60 to 4·44]) and depression (OR=2.28 (95% CI 2.06 to 2.51)). The lowest risk, though still significant, was for diabetes (OR=1·33 (95% CI 1.11 to 2.05)) and hypertension (OR=1.20 (95% CI 1.04 to 1.38)). After controlling for these potential confounding factors, among older people with chronic conditions, those with vision impairment were 2.20 to 4.04 times more likely to have poor health, compared with those without vision impairment (all p<0.001), with the exception of cancer (p=0.595). CONCLUSIONS: Higher prevalence of chronic conditions is strongly associated with vision impairment among older Chinese adults and poor health is strongly associated with vision impairment among people with chronic conditions.

Nanosecond pulsed electric fields impair viability and mucin expression in mucinous colorectal carcinoma cell.

Nanosecond pulsed electric fields (nsPEFs) are a non-thermal technology that can induce a myriad of biological responses and changes in cellular physiology. nsPEFs have gained significant attention as a novel cancer therapy. However, studies investigating the application of nsPEF in mucinous carcinomas are scarce. In this study, we explored several biological responses in two mucinous colorectal adenocarcinoma cell lines, LS 174T and HT-29, to nsPEF treatment. We determined the overall cell survival and viability rates following nsPEF treatment using CCK-8 and colony formation assays. We measured the intracellular effects of nsPEF treatment by analyzing cell cycle distribution, cell apoptosis and mitochondrial potential. We also analyzed mucin production at both mRNA and protein levels. Our results showed that nsPEF treatment significantly reduced mucinous cell viability in a dose-dependent manner. nsPEF treatment increased cell cycles arrest at G0/G1 while the proportion of G2/M cells gradually decreased. Cell apoptosis increased following nsPEF treatment with a clear loss in mitochondrial membrane potential. Furthermore, the protein expression of functional mucin family members decreased after nsPEF treatment. In conclusion, nsPEF treatment reduced MCRC cell viability, cell proliferation, and mucin protein production while promoted apoptosis. Our work is a pilot study that projects some insights into the potential clinical applications of nsPEFs in treating mucinous colorectal carcinoma.

Preparation of polymyxin B-loaded gellan-polylysine polyion complex fibers with high affinity to endotoxin.

Endotoxemia, a life-threatening disease affecting people worldwide, can be treated by hemoperfusion alone. New hemoperfusion materials with high biocompatibility and endotoxin-combination ability are always in demand. Herein, polymyxin B (PMB), a specific endotoxin binding molecule, was loaded onto gellan-polylysine polyion complex, and the obtained material was used in preparing wet-spun fibers. The tensile strength of the as-spun yarns (100 fibers) ranged from 1.49 N to -1.58 N and that of the dried and rewetted yarns ranged from 1.45 N to 1.56 N. The adsorption ability of the fibers with lipopolysaccharides from E. coli was 2.784 ± 0.036 EU/mg in simulated human body fluid and 2.452 ± 0.107 EU/mg in mouse plasma. The fibers showed no cytotoxicity toward U2OS cells and no hemolysis toward mouse blood. The influence of the fibers on the clotting time of mouse blood was negligible, and the blood cells were not adhesive to the fibers. Thus, the PMB-loaded gellan-polylysine complex fiber and its derivate fabrics can be used in hemoperfusion.

[Advances in microbial degradation of polybrominated diphenyl ethers (PBDEs)].

Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame-retardants in a variety of commercial products especially in the electronics and household industries. However, they are bioaccumulative, biotoxic and persistent, making them a globally distributed organic chemical toxin nowadays. Thus, it is extremely important to degrade PBDEs. This paper illustrates the research progress of metabolic pathways of PBDEs under both aerobic and anaerobic conditions, and also combines with in situ degradation studies to infer the degradation potential of archaea. The characteristics and comprehensive factors of various degradation pathways are analyzed. In addition, future researches on biodegradation mechanism of PBDEs, the design and application of PBDEs degradation system are discussed.

NMDA receptors are not required for pattern completion during associative memory recall.

Pattern completion, the ability to retrieve complete memories initiated by subsets of external cues, has been a major focus of many computation models. A previously study reports that such pattern completion requires NMDA receptors in the hippocampus. However, such a claim was derived from a non-inducible gene knockout experiment in which the NMDA receptors were absent throughout all stages of memory processes as well as animal's adult life. This raises the critical question regarding whether the previously described results were truly resulting from the requirement of the NMDA receptors in retrieval. Here, we have examined the role of the NMDA receptors in pattern completion via inducible knockout of NMDA receptors limited to the memory retrieval stage. By using two independent mouse lines, we found that inducible knockout mice, lacking NMDA receptor in either forebrain or hippocampus CA1 region at the time of memory retrieval, exhibited normal recall of associative spatial reference memory regardless of whether retrievals took place under full-cue or partial-cue conditions. Moreover, systemic antagonism of NMDA receptor during retention tests also had no effect on full-cue or partial-cue recall of spatial water maze memories. Thus, both genetic and pharmacological experiments collectively demonstrate that pattern completion during spatial associative memory recall does not require the NMDA receptor in the hippocampus or forebrain.

The different effects of over-expressing murine NMDA receptor 2B subunit in the forebrain on conditioned taste aversion.

The glutamate transmission system and the N-methyl-D-aspartate receptor (NMDA-R), in particular its 2B subunit (NR2B), have been reported to be possibly related to taste memory as a result of treatment with NMDA antagonists and agonists. In order to further study the role of the NR2B subunit in gustation memory, we applied four different taste aversive tasks to observe the behavior of a transgenic mice model in which the NR2B subunit was specifically over-expressed in the forebrain. We found that in both short- and long-term conditioned taste aversion (CTA) experiments, mice with forebrain expression of the NR2B transgene (Tg) showed significantly enhanced CTA 2 days after training. However, both the Tg and the wild-type (Wt) mice shared the same level of aversive memory on the 30th day after training. In both fast and slow extinction experiments, Tg mice maintained a higher CTA memory than that of control mice in most extinction trials. The third experiment, which involved testing the memory for familiar taste, demonstrated that NR2B augmentation had no benefit on the latent inhibition (LI) of CTA. In addition, the last experiment (two-taste LI) showed a suppression of enhanced CTA in Tg mice when the mice were exposed to both novel and familiar tastes. These data suggested that forebrain NR2B over-expression had different effects on gustatory learning and memory. The transgenic animals were only sensitive to novel but not familiar tastes, and up-regulation of NR2B resulted in enhanced CTA function for only a short period of time.