Intestinal dysbacteriosis contributes to persistent cognitive impairment after resolution of acute liver failure.

Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. This work aims to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure(ALF) mice before and after hepatic function recovery. Here, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we found that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. Additionally, fecal microbiota transplant from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, we found alterations in synaptic transmission in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results showed that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicated continuous care may be necessary for monitoring microbial imbalance even in ALF-induced HE patients whose liver function has recovered significantly.

The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030.

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019. Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software. Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030. Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.

Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice.

Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and ß-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.

Effects of Different Cultivation Modes on Morphological Traits and Correlations between Traits and Body Mass of Crayfish (Procambarus clarkii).

In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (D1), paddy field (D2), and aquaculture barrel (D3), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (X1), body length (X2), chelicerae length (X3), chelicerae weight (X4), cephalothorax length (X5), cephalothorax width (X6), cephalothorax height (X7), eye spacing (X8), caudal peduncle length (X9), and caudal peduncle weight (X10). We found that the coefficient of variation (CV) of X4 was the largest in each culture mode, and males (28.58%~38.67%) were larger than females (37.76%~66.74%). The CV of X4 of crayfish cultured in D1 and D2 was larger than that of D3. All traits except X8 were positively correlated with body weight (p < 0.05). After pathway analysis, we found that X4, X5, X7, and X10 were significantly correlated with the body weight of D1-♀; the equation was YD1-♀ = -29.803 + 1.249X4 + 0.505X5 + 0.701X7 + 1.483X10 (R2 = 0.947). However, X2, X4, and X6 were significantly correlated with the body weight of D1-♂; the equation was YD1-♂ = -40.881 + 0.39X2 + 0.845X4 + 1.142X6 (R2 = 0.927). In D2-♀, X1, X4, X5, and X10 were significantly correlated with body weight; the equation was YD2-♀ = -12.248 + 0.088X1 + 1.098X4 + 0.275X5 + 0.904X10 (R2 = 0.977). X4 and X5 played a major role in the body weight of D2-♂ with the equation: YD2-♂ = -24.871 + 1.177X4 + 0.902X5 (R2 = 0.973). X3 and X10 mainly contributed to the body weight of D3-♀ with the equation: YD3-♀ = -22.476 + 0.432X3 + 3.153X10 (R2 = 0.976). X1 and X4 mainly contributed to the body weight of D3-♂ with the equation: YD3-♂ = -34.434 + 0.363X1 + 0.669X4 (R2 = 0.918). Comparing the pathway analysis with the gray relation analysis, we could conclude that the traits most correlated with body weight in D1-♀ were X10 and X7; in D1-♂, X6; in D2-♀, X10, X1, and X5; in D2-♂, X5; in D3-♀, X10; and in D3-♂, X4 and X1.

Ultrafast Decay Dynamics of the 21ππ* Electronic State of N-Methyl-2-pyridone.

The ultrafast decay dynamics of N-methyl-2-pyridone upon excitation in the near-ultraviolet range of 261.5-227.9 nm is investigated using the femtosecond time-resolved photoelectron spectroscopy method. Irradiation at 261.5 nm prepares N-methyl-2-pyridone molecules with high vibrational levels in the 11ππ* state. The radiation-less decay to the ground state via internal conversion is suggested to be the dominant channel for the 11ππ* state with large vibrational excess energy, which is revealed by a lifetime of 1.6 ± 0.2 ps. As the pump wavelength decreases, we found that irradiation at 238.5 and 227.9 nm results in the population of the 21ππ* state. This is in agreement with the assignment of the vapor-phase UV absorption bands of N-methyl-2-pyridone. On the basis of the detailed analysis of our measured time-resolved photoelectron spectra at all pump wavelengths, we conclude that the 21ππ* state has an ultrashort lifetime of 50 ± 10 fs. In addition, the S1(11ππ*) state is subsequently populated via internal conversion and decays over a lifetime of 680-620 fs. The most probable whole deactivation pathway of the 21ππ* state is discussed. This experimental study provides new insights into the excitation energy-dependent decay dynamics of electronically excited N-methyl-2-pyridone.

Imaging demyelinated axons after spinal cord injuries with PET tracer [ 18 F]3F4AP.

Spinal cord injuries (SCI) often lead to lifelong disability. Among the various types of injuries, incomplete and discomplete injuries, where some axons remain intact, offer potential for recovery. However, demyelination of these spared axons can worsen disability. Demyelination is a reversible phenomenon, and drugs like 4-aminopyridine (4AP), which target K+ channels in demyelinated axons, show that conduction can be restored. Yet, accurately assessing and monitoring demyelination post-SCI remains challenging due to the lack of suitable imaging methods. In this study, we introduce a novel approach utilizing the positron emission tomography (PET) tracer, [ 18 F]3F4AP, specifically targeting K+ channels in demyelinated axons for SCI imaging. Rats with incomplete contusion injuries were imaged up to one month post-injury, revealing [ 18 F]3F4AP's exceptional sensitivity to injury and its ability to detect temporal changes. Further validation through autoradiography and immunohistochemistry confirmed [ 18 F]3F4AP's targeting of demyelinated axons. In a proof-of-concept study involving human subjects, [ 18 F]3F4AP differentiated between a severe and a largely recovered incomplete injury, indicating axonal loss and demyelination, respectively. Moreover, alterations in tracer delivery were evident on dynamic PET images, suggestive of differences in spinal cord blood flow between the injuries. In conclusion, [ 18 F]3F4AP demonstrates efficacy in detecting incomplete SCI in both animal models and humans. The potential for monitoring post-SCI demyelination changes and response to therapy underscores the utility of [ 18 F]3F4AP in advancing our understanding and management of spinal cord injuries.

Effects of replacing fishmeal with soybean meal on the immune and antioxidant capacity, and intestinal metabolic functions of red swamp crayfish Procambarus clarkii.

Excess utilization of plant protein sources in animal feed has been found to adversely affect the antioxidant properties and immunity of animals. While the role of gut microbes in plant protein-induced inflammation has been identified in various models, the specific mechanisms regulating gut microbes in crustaceans remain unclear. Accordingly, this study was designed to investigate the effects of replacing fishmeal with soybean meal (SM) on the hepatopancreas antioxidant and immune capacities, and gut microbial functions of crayfish, as well as the potential microbial regulatory mechanisms. 750 crayfish (4.00 g) were randomly divided into five groups: SS0, SS25, SS50, SS75, and SS100, and fed diets with different levels of soybean meal substituted for fishmeal for six weeks. High SM supplementation proved detrimental to maintaining hepatopancreas health, as indicated by an increase in hemolymph MDA content, GPT, and GOT activities, the observed rupture of hepatopancreas cell basement membranes, along with the decreased number of hepatopancreatic F cells. Moreover, crayfish subjected to high SM diets experienced obvious inflammation in hepatopancreas, together with up-regulated mRNA expression levels of nfkb, alf, and tlr (p<0.05), whereas the lzm mRNA expression level exhibited the highest value in the SS25 group. Furthermore, hepatopancreas antioxidant properties highly attenuated by the level of dietary SM substitution levels, as evidenced by the observed increase in MDA content (p<0.05), decrease in GSH content (p<0.05), and inhabitation of SOD, CAT, GPx, and GST activities (p<0.05), along with down-regulated hepatopancreas cat, gpx, gst, and mmnsod mRNA expression levels via inhibiting nrf2/keap1 pathway. Functional genes contributing to metabolism identified that high SM diets feeding significantly activated lipopolysaccharide biosynthesis, revealing gut dysfunction acted as the cause of inflammation. The global microbial co-occurrence network further indicated that the microbes contributing more to serum indicators and immunity were in module eigengene 17 (ME17). A structural equation model revealed that the genes related to alf directly drove the serum enzyme activities through microbes in ME17, with OTU399 and OTU533 identified as major biomarkers and classified into Proteobacteria that secrete endotoxins. To conclude, SM could replace 25 % of fishmeal in crayfish diets without negatively affecting immunity, and antioxidant capacity. Excessive SM levels contributed to gut dysfunction and weakened the innate immune system of crayfish.

Superior Li+ Kinetics by "Low-Activity-Solvent" Engineering for Stable Lithium Metal Batteries.

The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).

Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration.

Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment. ESI1 promotes remyelination in animal models of demyelination and enables de novo myelinogenesis on regenerated CNS axons. ESI1 treatment lengthened myelin sheaths in human iPSC-derived organoids and augmented (re)myelination in aged mice while reversing age-related cognitive decline. Multi-omics revealed that ESI1 induces an active chromatin landscape that activates myelinogenic pathways and reprograms metabolism. Notably, ESI1 triggered nuclear condensate formation of master lipid-metabolic regulators SREBP1/2, concentrating transcriptional co-activators to drive lipid/cholesterol biosynthesis. Our study highlights the potential of targeting epigenetic silencing to enable CNS myelin regeneration in demyelinating diseases and aging.

Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Experimental Generation of Spin-Photon Entanglement in Silicon Carbide.

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

Global disease burden linked to diet high in red meat and colorectal cancer from 1990 to 2019 and its prediction up to 2030.

Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

Insights into ultrafast decay dynamics of electronically excited pyridine-N-oxide.

The ultrafast decay dynamics of pyridine-N-oxide upon excitation in the near-ultraviolet range of 340.2-217.6 nm is investigated using the femtosecond time-resolved photoelectron imaging technique. The time-resolved photoelectron spectra and photoelectron angular distributions at all pump wavelengths are carefully analyzed and the following view is derived: at the longest pump wavelengths (340.2 and 325.6 nm), pyridine-N-oxide is excited to the S1(1ππ*) state with different vibrational levels. The depopulation rate of the S1 state shows a marked dependence on vibrational energy and mode, and the lifetime is in the range of 1.4-160 ps. At 289.8 and 280.5 nm, both the second 1ππ* state and the S1 state are initially prepared. The former has an extremely short lifetime of ∼60 fs, which indicates that the ultrafast deactivation pathway such as a rapid internal conversion to one close-lying state is its dominant decay channel, while the latter is at high levels of vibrational excitation and decays within the range of 380-520 fs. At the shortest pump wavelengths (227.3 and 217.6 nm), another excited state of Rydberg character is mostly excited. We assign this state to the 3s Rydberg state which has a lifetime of 0.55-2.2 ps. This study provides a comprehensive picture of the ultrafast excited-state decay dynamics of the photoexcited pyridine-N-oxide molecule.

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model.

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable "viscobeads" technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

Gut microbiota regulates hepatic ischemia-reperfusion injury-induced cognitive dysfunction via the HDAC2-ACSS2 axis in mice.

AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication. METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized. RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus. CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.

The secondary somatosensory cortex gates mechanical and heat sensitivity.

The cerebral cortex is vital for the processing and perception of sensory stimuli. In the somatosensory axis, information is received primarily by two distinct regions, the primary (S1) and secondary (S2) somatosensory cortices. Top-down circuits stemming from S1 can modulate mechanical and cooling but not heat stimuli such that circuit inhibition causes blunted perception. This suggests that responsiveness to particular somatosensory stimuli occurs in a modality specific fashion and we sought to determine additional cortical substrates. In this work, we identify in a mouse model that inhibition of S2 output increases mechanical and heat, but not cooling sensitivity, in contrast to S1. Combining 2-photon anatomical reconstruction with chemogenetic inhibition of specific S2 circuits, we discover that S2 projections to the secondary motor cortex (M2) govern mechanical and heat sensitivity without affecting motor performance or anxiety. Taken together, we show that S2 is an essential cortical structure that governs mechanical and heat sensitivity.

LINC00662 promotes melanoma progression by competitively binding miR-107 and activating the ß-catenin signaling pathway.

Melanoma is a highly malignant tumor in the body. Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of various tumors. Emerging evidence demonstrates the critical role of lncRNAs in melanoma development. In this study, we aimed to investigate the expression, biological function and regulatory mechanism of LINC00662 in melanomas. First, we found that LINC00662 was up-regulated in melanoma tissues and cell lines. High expression of LINC00662 in melanomas was associated with a poor patient prognosis. Silencing of LINC00662 suppressed the proliferation, migration, and invasion of melanoma cells in vitro and in vivo, while overexpression of LINC00662 promoted melanoma cell proliferation in vitro. Bioinformatics analysis, dual-luciferase assay, and RIP assay confirmed that LINC00662 competitively regulated miR-107. Silencing of LINC00662 upregulated miR-107 expression in a melanoma cell line. Inhibition of miR-107 significantly reversed the inhibitory effect of LINC00662 silencing on cell proliferation and migration. Furthermore, POU3F2 was validated as a downstream target of LINC00662/miR107 and was downregulated when LINC00662 was silenced. Overexpressing POU3F2 attenuated the effect of si-LINC00662 on cellular functions. In addition, the results also showed that the ß-catenin pathway was involved in a si-LINC00662-induced function in melanoma. Overall, our results confirmed that LINC00662 promoted melanoma progression by sponging miR107 and inducing POU3F2, highlighting the mechanism of the LINC00662/miR-107/POU3F2 axis in melanoma cell proliferation and invasion.

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.