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The hypothalamus plays a vital role in coordinating essential neuroendocrine, autonomic, and somatomotor responses for survival and reproduction. While previous studies have explored population-level projections of hypothalamic neurons, the specific innervation patterns of individual hypothalamic axons remain unclear. To understand the organization of hypothalamic axon projections, we conducted a comprehensive reconstruction of single-cell projectomes from 7,180 mouse hypothalamic neurons expressing specific neuropeptides. Our analysis identified 31 distinct subtypes based on projectome-defined characteristics, with many exhibiting long-range axon collateral projections to multiple brain regions. Notably, these subtypes selectively targeted specific subdomains within downstream areas, either unilaterally or bilaterally. Furthermore, we observed that individual peptidergic neuronal types encompassed multiple projectome-defined subtypes, explaining their diverse functional roles. Additionally, by examining intra-hypothalamic axon projections, we uncovered six modular subnetworks characterized by enriched intramodular connections and distinct preferences for downstream targets. This modular organization of the intra-hypothalamic network likely contributes to the coordinated organization of hypothalamic outputs. In summary, our comprehensive projectome analysis reveals the organizational principles governing hypothalamic axon projections, providing a framework for understanding the neural circuit mechanisms underlying the diverse and coordinated functions of the hypothalamus.

In this work, the effects of proton-induced trap evolution on the electrical performances of AlGaN/GaN metal–insulator–semiconductor (MIS) high-electron-mobility-transistors (HEMTs) have been investigated in detail. Contrary to observed proton-induced degradation in sheet electron density (ns), carrier mobility (μn), and sheet resistance (RSH), a significant improvement in gate leakage current (IG) and off-state drain–source breakdown voltage (BVDS) is found in irradiated devices. The low-frequency noise (LFN) results show that the density of traps in the AlGaN layer and AlGaN/GaN interface increases after irradiation, which leads to a degradation in ns, μn, and RSH and an improvement in BVDS due to enhanced electron trapping and depletion. Furthermore, the measurement results obtained from the frequency-dependent conductance technique show that irradiated devices exhibit decreased trap density (DT) at the insulator/semiconductor interface with hardly changed trap energy level (ET), which confirms the observed proton-induced decrease in IG. An increase in DT at the AlGaN/GaN interface is also found after irradiation, which is consistent with LFN results. These traps with deeper ET induce a serious Coulomb scattering effect. This work provides valuable information for the systematic understanding of the proton irradiation effect of AlGaN/GaN MIS-HEMTs.

Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied to a broad range of unactivated alkenes remains challenging. Herein, we report a NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes to access β- or γ-branched alkyl carboxylic acids and β-, γ- or δ-branched alkyl amines. A broad range of alkyl iodides and bromides with different functional groups can be installed with excellent regiocontrol and availability for site-selective late-stage functionalization of biorelevant molecules. Under modified reaction conditions with NiCl2(PPh3)2 as the catalyst, migratory hydroalkylation takes place to provide β- (rather than γ-) branched products. The keys to success are the use of aminoquinoline and picolinamide as suitable directing groups and combined experimental and computational studies of ligand effects on the regioselectivity and detailed reaction mechanisms.

During the process of synaptic formation, neurons require not only certain principles for selecting partners to form synapses but also additional mechanisms to avoid undesired cells. However, the means to get around unwanted partners remains largely unknown. In this study, we have identified that the combinatorial expression of clustered protocadherin gammas (γ-PCDHs) is essential in regulating such specificity in the mouse neocortex. Using single-cell sequencing from the 5-prime end, we revealed the combinatorial expression pattern of γ-PCDH variable isoforms in neocortical neurons. Whole-cell patch-clamp recordings demonstrated that increasing the similarity level of this combinatorial pattern in neurons reduced their synaptic connectivity. Our findings reveal a delicate molecular mechanism for assembling the neural network in the mouse neocortex.

To investigate the complications of tourniquet in the clinical application of lower tibiofibular fracture.From June 2018 to September 2019, 33 cases of closed lower tibiofibular fractures (AO type 43A) were treated with plates and screws and were divided into two groups according to whether pueumatic tourniquet was used:16 cases in the observation group, 13 males and 3 females, aged 18 to 69 (38.8±17.0) years, the operation time after injury was (6.9±1.7) days, and tourniquet was not used during operation. There were 17 cases in the control group, 13 males and 4 females, aged from 21 to 71 (43.8±12.4) years, the operation time after injury was (6.5±1.0) days, automatic pneumatic tourniquetwas routinely used in the operation. The operation time, blood loss, postoperative swelling, pain and other complications were compared between two groups.Total of 33 patients were followed up for an average of 15 months. There was no significant difference in operation time and blood loss between two groups (The fracture of lower tibiofibular segment is superficial and easy to be exposed and fixed during operation. In order to avoid tourniquet complications, it is not recommended to use air bag tourniquet routinely or minimize the application time of tourniquet.

Dissecting neural connectivity patterns within local brain regions is an essential step to understanding the function of the brain.

Traditional star image identification methods use adjacent stellar angular distances to form identification features. The missed detection of high-magnitude stars due to noise interference affects their identification accuracy. We propose a star image identification method based on perceptual hash features. The multiple Gaussian distribution superposition constructed by stars within a certain range around the center star forms the unique standard identification image of that star, in which the brightness distribution is determined by stellar magnitudes. The perceptual hash feature of the standard identification image is then used as a standard identification feature. The observation feature is extracted from the identification image as-constructed by the star points extracted from the star image. Finally, the observation feature is matched with the standard feature to identify the star image. Simulation results indicate that the proposed method can efficiently identify star images and effectively prevent missed stars from influencing the matching results.

Background Numerous studies have sought associations between matrix metalloproteinase 9 (MMP-9) polymorphisms and breast cancer risk. However, these studies have yielded conflicting results. Hence, we performed an updated meta-analysis to clarify the effects of four MMP-9 gene polymorphisms (rs3918242, rs2250889, rs3787268, and rs17576) on breast cancer risk. Methods A comprehensive literature search for eligible studies was conducted in five electronic databases, including PubMed, Embase and Web of Science, up to March 1, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations in random-effects models. For the reduction of type I errors, a trial sequential analysis (TSA) was performed. Results Twenty-one studies (8813 breast cancer cases and 9323 controls) were included in the quantitative analysis. For rs3918242, the overall ORs were significant under allelic comparison (OR A vs. G = 1.34; 95% CI 1.03, 1.74, P = 0.028) and the recessive genetic model (OR AA vs. GG+GA = 1.40; 95% CI 1.06, 1.84, P = 0.016). For rs2250889, the ORs were significant under homozygote comparison (OR GG vs. CC = 2.57; 95% CI 1.22, 5.42, P = 0.013), heterozygote comparison (OR GC vs. CC = 2.48; 95% CI 1.17, 5.23, P = 0.018), and the dominant genetic model (OR GG+GC vs. CC = 2.53; 95% CI 1.23, 5.20, P = 0.012). No associations were observed for rs3787268 or rs17576. The subgroup analyses indicated that the risk effect of the rs3918242 A allele was observed only among Asians. TSA showed that the findings for rs3918242, rs3787268, and rs17576 were robust, but many more patients are needed before definitive conclusions can be made for rs2250889. Conclusion Our meta-analysis suggests that MMP-9 rs3918242, but not rs3787268 and rs17576 polymorphisms, may be risk factors for breast cancer. The effect of rs2250889 needs further confirmation with a larger sample size.

Classical consolidation theory ignores the influence of soil liquid phase acceleration. This paper considers the influence of liquid phase acceleration on the stress balance equation during the consolidation of soil, obtains the one-dimensional equation governing quasi-hydrostatic consolidation under large deformation with the consideration of the inertia of the liquid phase, and solves the governing equations by finite element method. The calculation results show that the liquid phase inertia effect of the soil will cause excess pore pressure in the soil, obviously increasing in the initial stage of consolidation, and the self-weight of soil exerts an influence on the excess pore pressure at the later stages of consolidation. The liquid phase inertia effect parameter Dc determines the strength of the liquid phase inertia effect. A larger Dc value results in a larger increase in the excess pore pressure, and the later the liquid phase inertial effect occurs, the longer the duration is. In the large strain consolidation analysis, especially at the initial stage of consolidation, it is necessary to consider the liquid phase inertia effect of the soil.

On-demand shared mobility services such as Uber and microtransit are steadily penetrating the worldwide market for traditional dispatched taxi services. Hence, taxi companies are seeking ways to compete. This study mined large-scale mobility data from connected taxis to discover beneficial patterns that may inform strategies to improve dispatch taxi business. It is not practical to manually clean and filter large-scale mobility data that contains GPS information. Therefore, this research contributes and demonstrates an automated method of data cleaning and filtering that is suitable for such types of datasets. The cleaning method defines three filter variables and applies a layered statistical filtering technique to eliminate outlier records that do not contribute to distributions that match expected theoretical distributions of the variables. Chi-squared statistical tests evaluate the quality of the cleaned data by comparing the distribution of the three variables with their expected distributions. The overall cleaning method removed approximately 5% of the data, which consisted of errors that were obvious and others that were poor quality outliers. Subsequently, mining the cleaned data revealed that trip production in Dubai peaks for the case when only the same two drivers operate the same taxi. This finding would not have been possible without access to proprietary data that contains unique identifiers for both drivers and taxis. Datasets that identify individual drivers are not publicly available.

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

Summary Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Muller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson’s disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.

After the mechanization upgrade of Yongjing Coal Mine, the original extraction method cannot solve the problem of gas. According to the actual production conditions of the mine, the source and composition ratio of gas emission are analyzed.By combining with the gas extraction method before upgrading and transformation, it is of great importance to determine the appropriate comprehensive gas extraction method and optimize the gas extraction parameters for improving the gas extraction effect and eliminating the risk of gas outburst.

C26H28Cl2N2O3, monoclinic, P21/c (no. 14), a = 13.422(3) Å, b = 7.0011(14) Å, c = 26.249(5) Å, β = 101.06(3)°, V = 2420.8(9) Å3, Z = 4, R gt(F) = 0.0516, wR ref(F 2) = 0.1370, T = 296 K.

This paper takes the ultra-low permeability sandstone reservoir of Jingbian oilfield in Ordos Basin as the research object, analyzes the petrological characteristics, diagenesis, physical characteristics and pore structure characteristics of the reservoir, and carries out reservoir sensitivity evaluation by using rock casting thin sections, X-ray diffraction, and sensitive flow experiments. The research results show that the ultra-low permeability Chang 6 sandstone reservoir has weak velocity sensitivity, medium-weak water sensitivity, weak salt sensitivity, weak alkali sensitivity and strong acid sensitivity; the damage mechanism of reservoir sensitivity mainly depends on the composition of clay minerals and pore structure after diagenesis. The clay mineral content from high to low is chlorite, illite, a small amount of illite / smectite layer, and kaolinite, of which the chlorite content is as high as 75 %; the reservoir has poor physical properties, the types of small hole-thin throat and small hole-fine throat. The reservoir is prone to blockage such as bridge plugging. Therefore, ultra-low permeability sandstone reservoirs are prone to different degrees of sensitivity. The reservoir characteristics are consistent with the reservoir sensitivity evaluation results.

The statistics and analysis of mine gas extraction is very important for mine gas control, which provides a basis for the formulation of mine gas extraction plan. Because of its simple and convenient characteristics, it is favored by the engineering and technical personnel in the coal mine field, and has been widely used, and achieved good results. Based on the statistics of gas drainage in Weijiadi Coal Mine from 2008 to 2018, the characteristics and quantity of gas emission are analyzed according to the statistical results of gas drainage in Weijiadi Coal Mine, and the characteristics of gas emission in the process of driving in the main mining seam are predicted, and the mathematics relations of the length of driving roadway and the quantity of gas emission is obtained.

In view of the coupling problem of gas and coal spontaneous combustion in goaf of 2302 coal mining face in Weijiadi Coal Mine in Jingyuan Coal Area, if the control is not in place, it may cause serious accidents such as gas explosion. By means of fluent simulation, the spontaneous combustion period and oxygen distribution of residual coal in goaf are obtained, and the minimum advancing speed of coal mining face to prevent spontaneous combustion in goaf is calculated to be 1.43m/d. By implementing fire prevention measures such as blocking air leakage in upper and lower corners, grouting and nitrogen injection in goaf, the oxygen concentration in goaf is controlled within 11%, and the spontaneous combustion zone of oxidation is fast. Transferring to asphyxiation zone and preventing the residual coal from firing in goaf are of great significance for ensuring the safety of mine production.

Taking 1302 fully mechanized caving face of Weijiadi Coal Mine as the research object, aiming at the characteristics of large gas emission and frequent gas exceeding limit during mining, this paper analyzed the difficult problems of gas control in working face, determined the theoretical height of caving zone and fissure zone of working face according to the gas cascade control mode formulated by Weijiadi Coal Mine and the principle of pressure relief gas, and inspected the “three zones”. The reasonable horizon and arrangement of drilling holes along the strike of large diameter and high position rocks are determined. The field practice results show that the gas extraction technology of large diameter and high rock trending borehole has good extraction effect, the maximum gas concentration is 26.5% and the maximum gas extraction volume is 14000 m3. It effectively solves the problem of return air flow and upper corner gas exceeding the limit. The gas concentration of return air flow is basically kept at 0.2%∼0.25%, which ensures the safety of mine production.

China is rich in coal resources, especially in Northwest China. However, due to the complex geological conditions, some low permeability and high gas seams often accompany abnormal gas emission during mining, which poses a serious threat to the safety of coal mine. This paper takes East 102 working face of Weijiadi Coal Mine in Jingyuan mining area of Gansu Province as the research object. Aiming at the abnormal gas emission phenomenon during the initial discharge period of working face, the causes of abnormal gas emission are analyzed. The prevention of abnormal gas emission should be carried out from five aspects: strengthening ventilation management, perfecting gas extraction system, perfecting safety monitoring and control system, strengthening power supply management and emergency management on site.

The division of gas geological units in coal mine is the basis of studying the occurrence law of gas geology in coal mine field, which is of great significance to the prediction of regional gas content and gas emission. Taking Weijiadi coalfield in Jingyuan mining area of Gansu Province as an object, this paper divides the coalfield into gas geological units, according to the gas content of coal seams in different regions, targeted gas extraction measures are implemented, gas cascade control is implemented, regional gas abnormal emission is strictly prevented, and mine safety production is ensured.

Abnormal gas emission is a common gas phenomenon in coal mining face of gas mine. In order to prevent gas accidents, on the one hand, gas extraction measures are adopted to reduce or avoid abnormal gas emission; on the other hand, when abnormal gas emission is unavoidable, in order to prevent abnormal gas emission from occurring gas explosion accident by electric spark, non-cost cutting is adopted. Emergency measures such as power supply for quality and safety electrical equipment are taken as the second line of defense. Aiming at the abnormal gas emission phenomenon in East 102 coal face of Weijiadi Coal Mine, in order to avoid the gas explosion accident during the abnormal gas gushing period, the emergency measures for gas abnormal emission were expounded from the aspects of gas electric blockade, power cut and evacuation.

U0126 (1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene), a widely used mitogen-activated protein kinase kinase (MEK) inhibitor, was found to accelerate voltage-gated K+ channel (KV) inactivation in heterologous cells expressing several types of KV. The goal of this study was to examine whether U0126 at a concentration thought to specifically inhibit MEK signaling also inhibits KV in native neurons of primary cultures or brain slices. U0126 caused a dose-dependent inhibition of both the transient (IA) and sustained (IDR) components of K+ currents in hippocampal neurons. U0126 also exhibited much higher potency on the IA and IDR than the classical KV blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Consistent with its inhibitory effect on KV, U0126 broadened action potential duration, profoundly affected the repolarizing phase, and dramatically reduced firing frequency in response to current pulse injections. Despite the potent and reversible action of U0126 on Kv channels, PD98059, a structurally-unrelated MEK inhibitor, did not induce such an effect, suggesting U0126 may act independently of MEK inhibition. Together, these results raise cautions for using U0126 as a specific inhibitor for studying MEK signaling in neurons; on the other hand, further studies on the blocking mechanisms of U0126 as a potent inhibitor of KV may provide useful insights into the structure-function relationship of KV in general.

AIM: To study clinical reference value of retinal microvascular changes in patients with cerebral microbleeds(CMBs)and discuss its clinical significance. METHODS:From January 2012 to December 2013, 125 hospitalized patients were collected, including 81 cases were male, 44 cases were female, mean age 76.3±11.2 years old. For all patients, functions of liver and kidney, blood-lipoids, blood sugar and blood biochemical examination were tested, and fundus photography and cerebral MR was done. According to the fundus camera eyes, retinal arteriolar equivalent(RAE), retinal venular equivalent(RVE), retinal vein diameter ratio(AVR)and arteriovenous crossing sign(AVN)were identified, CMBs were classified with cerebral MRI. All the data were processed by SPSS statistical software. RESULTS: The central retinal arteriolar equivalent(CRAE), central retinal venular equivalent(CRVE)and AVR values in the eyes were found no statistical difference(PPCOCLUSION: The results show that retinal microvascular changes, especially small retinal vein arteriovenous cross width, and arteriovenous crossing phenomenon, in which CMBs will happen more likely. After sex, age, hypertension and hyperglycemia in patients with traditional cardiovascular risk factors being ruled out, the retinal microvascular changes are still relatively factors of CMB's occurrence.

Mold shell with higher thermal conductivity was introduced in the article. Reinforced by the carbon fiber, the new type sol silicate mold shell could be made with much less layers while without reducing its strength. Therefore, the new-type mold shell should have higher thermal conductivity. Then measure its thickness, bend strength, analyze the dendritic crystal of the casting manufactured with the new-type mold shell. It was proved that the thickness had reduced by 25% and the bend strength did not decrease. And it performs better in the detection: the dendrite crystals are refined, the primary and secondary dendrite arm space are decreased, the secondary dendrite arms are restrained.

In Weijiadi Coal Mine, the No.2 coal seam is uncovered by the Donger return air shaft. According to the concept of “regional measures first, local measures supplement”, the measures are taken strictly in the outburst seam, the gas pressure P=0.2MPa and the gas content W=1.4729m3/t in the coal seam are determined by preconstruction prediction drilling, and there are no gas dynamic phenomena such as drilling jam and sticking in the drilling process. It is proved that there is no outburst danger, and then it is implemented according to the local “four in one” outburst prevention measures. The maximum gas pressure determined is 0.2 MPa in the working face, and the validity check is still no outburst danger. Finally, safety protection devices are installed in the working face to ensure the No.2 coal seam to be uncovered smoothly by return air shaft.