Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes.

Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.

African lungfish genome sheds light on the vertebrate water-to-land transition.

Lungfishes are the closest extant relatives of tetrapods and preserve ancestral traits linked with the water-to-land transition. However, their huge genome sizes have hindered understanding of this key transition in evolution. Here, we report a 40-Gb chromosome-level assembly of the African lungfish (Protopterus annectens) genome, which is the largest genome assembly ever reported and has a contig and chromosome N50 of 1.60 Mb and 2.81 Gb, respectively. The large size of the lungfish genome is due mainly to retrotransposons. Genes with ultra-long length show similar expression levels to other genes, indicating that lungfishes have evolved high transcription efficacy to keep gene expression balanced. Together with transcriptome and experimental data, we identified potential genes and regulatory elements related to such terrestrial adaptation traits as pulmonary surfactant, anxiolytic ability, pentadactyl limbs, and pharyngeal remodeling. Our results provide insights and key resources for understanding the evolutionary pathway leading from fishes to humans.

Mechanochemical Synthesis of Cuprous Complexes for X-ray Scintillation and Imaging.

Cuprous complex scintillators show promise for X-ray detection with abundant raw materials, diverse luminescent mechanisms, and adjustable structures. However, their synthesis typically requires a significant amount of organic solvents, which conflict with green chemistry principles. Herein, we present the synthesis of two high-performance cuprous complex scintillators using a simple mechanochemical method for the first time, namely [CuI(PPh3)2R] (R = 4-phenylpyridine hydroiodide (PH, Cu-1) and 4-(4-bromophenyl)pyridine hydroiodide (PH-Br, Cu-2). Both materials demonstrated remarkable scintillation performances, exhibiting radioluminescence (RL) intensities 1.52 times (Cu-1) and 2.52 times (Cu-2) greater than those of Bi4Ge3O12 (BGO), respectively. Compared to Cu-1, the enhanced RL performance of Cu-2 can be ascribed to its elevated quantum yield of 51.54%, significantly surpassing that of Cu-1 at 37.75%. This excellent luminescent performance is derived from the introduction of PH-Br, providing a more diverse array of intermolecular interactions that effectively constrain molecular vibration and rotation, further suppressing the nonradiative transition process. Furthermore, Cu-2 powder can be prepared into scintillator film with excellent X-ray imaging capabilities. This work establishes a pathway for the rapid, eco-friendly, and cost-effective synthesis of high-performance cuprous complex scintillators.

Toxicokinetics, in vivo metabolic profiling and tissue distribution of chlorfenapyr in mice.

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t1/2), area under the curve (AUC) and peak concentration (Cmax) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.

BY-SLAM: Dynamic Visual SLAM System Based on BEBLID and Semantic Information Extraction.

SLAM is a critical technology for enabling autonomous navigation and positioning in unmanned vehicles. Traditional visual simultaneous localization and mapping algorithms are built upon the assumption of a static scene, overlooking the impact of dynamic targets within real-world environments. Interference from dynamic targets can significantly degrade the system's localization accuracy or even lead to tracking failure. To address these issues, we propose a dynamic visual SLAM system named BY-SLAM, which is based on BEBLID and semantic information extraction. Initially, the BEBLID descriptor is introduced to describe Oriented FAST feature points, enhancing both feature point matching accuracy and speed. Subsequently, FasterNet replaces the backbone network of YOLOv8s to expedite semantic information extraction. By using the results of DBSCAN clustering object detection, a more refined semantic mask is obtained. Finally, by leveraging the semantic mask and epipolar constraints, dynamic feature points are discerned and eliminated, allowing for the utilization of only static feature points for pose estimation and the construction of a dense 3D map that excludes dynamic targets. Experimental evaluations are conducted on both the TUM RGB-D dataset and real-world scenarios and demonstrate the effectiveness of the proposed algorithm at filtering out dynamic targets within the scenes. On average, the localization accuracy for the TUM RGB-D dataset improves by 95.53% compared to ORB-SLAM3. Comparative analyses against classical dynamic SLAM systems further corroborate the improvement in localization accuracy, map readability, and robustness achieved by BY-SLAM.

African Suid Genomes Provide Insights into the Local Adaptation to Diverse African Environments.

African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.

3 × 1 fiber signal combiner with high beam quality Gaussian-like beam for a 10kW-level fiber laser.

We present the design and fabrication of a 3 × 1 signal combiner with high beam quality based on supermode theory. For improving beam quality, the fiber with core diameter of 34 µm and numerical aperture of 0.11 is first chosen as the output fiber. An 8.89 kW output laser with a power transmission efficiency of 97.2% and a low temperature rise coefficient of 3.5 °C/ kW at >8 kW is obtained when the combiner launched by three Yb-doped fiber lasers. In addition, the energy density distribution of the output beam is Gaussian-like and M2 factor is 2.32, which is the best beam quality compared with the presented signal combiners for high power laser to the best of our knowledge.

Extended L-band 4-Core Er/Yb co-doped fiber amplifier based on 1018†nm cladding pumping.

The extended L-band 4-core Er/Yb co-doped fiber and amplifier (MC-EYDFA) is first proposed and demonstrated, to the best of our knowledge, for space division multiplexing combined with wavelength division multiplexing application. The fiber core co-doped with Er/Yb/P is adopted for bandwidth expansion, and the long wavelength extends to 1625 nm. Numerical simulations further show that efficient amplification and higher saturation power are achieved with the 1018 nm cladding pumping. Based on the integrated 4-core fiber amplifier, an average gain of ∼22 dB covering 1575-1625 nm is experimentally obtained with a 4 W pump power and a 3 dBm total signal power, and the max core-dependent gain (CDG) variation is measured to be 1.7 dB.

Er/Yb co-doped 345-W all-fiber laser at 1535 nm using hybrid fiber.

The 1.5-µm fiber laser is widely used in the fields of laser lidar, remote sensing, and gas monitoring because of its advantages of being eye-safe and exhibiting low atmospheric transmission loss. However, due to the ∼1-µm amplified spontaneous emission (ASE) of the Er/Yb co-doped fiber (EYDF), it is difficult to improve the laser power. Here, we simulated the effect of the Er3+ concentration and the seed power on ∼1-µm ASE, and fabricated a large mode area EYDF by the modified chemical vapor deposition process. Additionally, a piece of ytterbium-doped fiber was introduced into the master oscillator power amplifier (MOPA) configuration to absorb the generated ∼1-µm ASE simultaneously. Experimental results show that an output power of 345 W with a slope efficiency of 43% at 1535 nm is obtained in an all-fiber configuration, profiting from effective suppression of ∼ 1-µm ASE. To the best of our knowledge, this is the highest output power available with an Er/Yb co-doped fiber from an all-fiber MOPA configuration.

Analysis of initial sandplay characteristics among university students with different levels of loneliness.

BACKGROUND AND OBJECTIVE: Loneliness is detrimental to mental health, with university students at higher risk of feeling lonely than other population groups. The mental health of college students is a hot topic at present. Despite numerous studies exploring interventions for loneliness among university students. However, little research has explored early psychological manifestations of university students with different levels of loneliness. Despite numerous studies exploring interventions for loneliness among university students, little research has explored early psychological manifestations of university students with different levels of loneliness. Initial sandplay is a good tool to reveal psychological activity. Therefore, our study aims to explore the characteristics of initial sandplay application among university students with different levels of loneliness. METHODS: We recruited 60 volunteers from a university to perform a sandplay experiment from January to April 2021. The UCLA Loneliness Scale measured the levels of loneliness. These 60 participants were divided into the experimental group (n = 30) and control group (n = 30) according to their levels of loneliness. The experimental group included participants with a scale score of more than 44. Other participants with a scale score of less than 44 belong to the control group. We recorded their sandplay artwork and statistically analyzed it by the Sandplay Process Record Form. Group comparisons were performed using the t-test or Wilcoxon rank-sum test for continuous variables, and the chi-square test or Fisher's exact test for categorical variables. The logistic regression analysis by forward stepwise method was conducted to analyze the sandplay theme features for loneliness. RESULTS: Regarding the sandplay tools, the experimental group used fewer transportation tools (t=-3.608, p < 0.01) and more natural elements (t = 2.176, p < 0.05) than the control group. Moreover, the experimental group created more natural scenes (χ2 = 4.310, p < 0.05) and used less of the lower left (χ2 = 4.593, p < 0.05) and lower right (χ2 = 5.934, p < 0.05) spaces. With regards to sand changes, the experimental group was less likely than the control group to make substantial changes (χ2 = 5.711, p < 0.05) and more likely to make almost no changes (χ2 = 4.022, p < 0.05). In terms of the themes, the experimental group was more likely to exhibit sandplay artwork themes of emptiness (χ2 = 8.864, p < 0.05) and neglect (χ2 = 6.667, p < 0.05), and less likely to show themes of energy (χ2 = 5.079, p < 0.05). In the logistic regression analysis of the sandplay themes, emptiness (OR = 5.714, 95%CI: 1.724-18.944, p = 0.003) and neglect (OR = 7.000, 95%CI: 1.381-35.479, p = 0.010) were demonstrated a nominal association with high levels of loneliness among both groups (F = 16.091, p < 0.01, ΔR2 = 0.193), but failed to pass the Bonferroni testing correction (p threshold < 0.0025). CONCLUSION: University students with higher degree of loneliness do not like to drastic changes and prefer to use natural elements in element selection, while the control group likes to drastic changes and prefers to use transportation tools in element selection. Regression analysis of sandplay theme features revealed emptines and neglect may as significant associated factors for loneliness. We propose sandplay characteristics can help identify university students with different levels of loneliness during psychological evaluations. Therefore, it is important that the school and healthcare systems assist college students in identifying the loneliness through initial sandplay and carrying on the necessary psychological counseling to the lonely student population.

Structural Variants Selected during Yak Domestication Inferred from Long-Read Whole-Genome Sequencing.

Structural variants (SVs) represent an important genetic resource for both natural and artificial selection. Here we present a chromosome-scale reference genome for domestic yak (Bos grunniens) that has longer contigs and scaffolds (N50 44.72 and 114.39 Mb, respectively) than reported for any other ruminant genome. We further obtained long-read resequencing data for 6 wild and 23 domestic yaks and constructed a genetic SV map of 372,220 SVs that covers the geographic range of the yaks. The majority of the SVs contains repetitive sequences and several are in or near genes. By comparing SVs in domestic and wild yaks, we identified genes that are predominantly related to the nervous system, behavior, immunity, and reproduction and may have been targeted by artificial selection during yak domestication. These findings provide new insights in the domestication of animals living at high altitude and highlight the importance of SVs in animal domestication.

The Genomes of Two Billfishes Provide Insights into the Evolution of Endothermy in Teleosts.

Endothermy is a typical convergent phenomenon which has evolved independently at least eight times in vertebrates, and is of significant advantage to organisms in extending their niches. However, how vertebrates other than mammals or birds, especially teleosts, achieve endothermy has not previously been fully understood. In this study, we sequenced the genomes of two billfishes (swordfish and sailfish), members of a representative lineage of endothermic teleosts. Convergent amino acid replacements were observed in proteins related to heat production and the visual system in two endothermic teleost lineages, billfishes and tunas. The billfish-specific genetic innovations were found to be associated with heat exchange, thermoregulation, and the specialized morphology, including elongated bill, enlarged dorsal fin in sailfish and loss of the pelvic fin in swordfish.

Bruceine A protects against diabetic kidney disease via inhibiting galectin-1.

Bruceine A is a natural quassinoid compound extracted from the fruit of the Traditional Chinese Medicine Brucea javanica (L.) Merr. that has various types of various biological activities. However, whether the compound has a protective effect on diabetic kidney disease remains unknown. Galectin-1 is actively involved in a variety of chronic inflammation-relevant human diseases including diabetic kidney disease. Here, we identified Bruceine A as a kidney protective molecule against a model of diabetic kidney disease in db/db mice with potent anti-inflammatory activity both in vitro and in vivo. Mechanistically, by selectively binding to the conserved carbohydrate-recognition domain of galectin-1 and disrupting the interaction between galectin-1 and the receptor for activated protein C kinase 1, Bruceine A was found to inhibit galectin-1-mediated inflammatory signal transduction under high glucose stress in rat mesangial HBZY-1 cells. Thus, our findings reveal Bruceine A as an unidentified galectin-1 inhibitor affording significant protection against diabetic kidney disease and may provide novel pharmacological therapeutics for the disease.

High-efficiency cladding-pumped 4-core erbium-doped fiber with a pedestal for space division multiplexing amplification.

A cladding-pumped 4-core erbium-doped fiber (4C-EDF) with a pedestal structure has been firstly, to the best of our knowledge, proposed and fabricated for space division multiplexing (SDM) amplification. The numerical simulation shows that the index-raised pedestal around the fiber core can improve power conversion efficiency (PCE) by enhancing pump power usage. Compared with conventional 4C-EDF, the 4C-EDF with a pedestal has a gain improvement of 4.5 dB and a PCE enhancement of 91.8%, according to the experimental results (pedestal fiber: 9.55%, conventional fiber: 4.98%). For a 6 dBm total input signal power at L-band and a 7.8 W pump power at 976 nm, the pedestal 4C-EDF shows an average gain of 25 dB and an average noise figure (NF) of 6.5 dB over all cores in the wavelength range of 1570.41 nm to 1610.87 nm. The core-to-core gain variation is less than 2 dB.

Extended L-band few-mode Er/Yb Co-doped fiber amplifier with a cladding-pumped pseudo-two-stage configuration.

Spatial division multiplexing (SDM) is one of the most important technologies that may help to solve the future capacity crisis. However, to date, SDM optical amplification is still a challenge for its application. Herein, we numerically and experimentally demonstrated a few-mode Er/Yb co-doped fiber amplifier (FM-EYDFA) for extended L-band operation. A double cladding Er/Yb co-doped fiber was fabricated to expand the L-band bandwidth and a novel, to the best of our knowledge, cladding-pumped pseudo-two-stage amplification configuration was proposed to enhance the L-band gain. With an initial signal power of -16.8 dBm and an injected pump power of 8.8 W at 940 nm, the 20-dB gain range was covered to 1620 nm for two-mode groups of LP01 and LP11. Importantly, the average gain of 25 dB and average differential modal gain (DMG) of <1 dB were obtained in the wavelength range of 1570-1620 nm for all modes. Our results suggest that the cladding-pumped pseudo-two-stage amplifier based on Er/Yb co-doped fiber providing low DMG, and broad bandwidth has a great potential for increasing the future SDM capacity.

A physicochemical model of odor sampling.

We present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling. The outcome of these competing ligand-receptor interactions yields a pattern of receptor activation levels, thereafter mapped to glomerular presynaptic activation levels based on the convergence of sensory neuron axons. The metric of greatest interest is the mean discrimination sensitivity, a measure of how effectively the olfactory system at this level is able to recognize a small change in the physicochemical quality of a stimulus. This model presents several significant outcomes, both expected and surprising. First, adding additional receptors reliably improves the system's discrimination sensitivity. Second, in contrast, adding additional ligands to an odorscene initially can improve discrimination sensitivity, but eventually will reduce it as the number of ligands increases. Third, the presence of antagonistic ligand-receptor interactions produced clear benefits for sensory system performance, generating higher absolute discrimination sensitivities and increasing the numbers of competing ligands that could be present before discrimination sensitivity began to be impaired. Finally, the model correctly reflects and explains the modest reduction in odor discrimination sensitivity exhibited by transgenic mice in which the specificity of glomerular targeting by primary olfactory neurons is partially disrupted.

Extending the L-band amplification to 1623 nm using Er/Yb/P co-doped phosphosilicate fiber.

The gain bandwidth of the erbium-doped fiber amplifier limits the enhancement of the transmission capacity in optical fiber communication systems. This Letter reports an erbium-ytterbium co-doped phosphosilicate fiber, which is expected to increase transmission capacity by extending the L-band gain bandwidth to 1623 nm. The fiber was fabricated by modified chemical vapor deposition combined with solution doping technology. The mechanism of bandwidth-expansion by inhibiting the signal excited-state absorption was investigated. When the signal power and pump power were maintained at -3.7dBm and ∼720mW at 1480 nm, the 20 dB gain range was extended out to 1623 nm. Additionally, the noise figure at 1623 nm decreased to 6.01 dB, with 23 dBm saturated output power. The results show that the erbium-ytterbium co-doped phosphosilicate fiber has a great potential for extending L-band amplification.

Histone Lysine-to-Methionine Mutation as Anticancer Drug Target.

Histone modification stands for a vital genetic information form, which shows tight correlation with the modulation of normal physiological activities by genes. Abnormal regulation of histone methylation due to histone modification enzyme changes and histone mutations plays an important role in the development of cancer. Histone mutations, especially H3K27M and H3K36M, have been identified in various cancers such as pediatric DIPG (diffuse intrinsic pontine glioma) and chondroblastoma respectively. "K to M" mutation results overall downregulation of methylation on these lysine residues. Also, "K to M" mutant histones can inhibit the enzymatic activity of the responsible HMT (histone methyltransferase); for instance, SETD2 indicates H3K36 methylation, and Ezh2 represents H3K27 methylation. In-depth analysis of the mechanism of tumor formation triggered by the K to M mutation results in possible targeted therapies. This chapter is going to briefly introduce the mechanism of histone lysine-to-methionine mutation and review the recently identified targeted therapeutic strategies.

Covalent modification of Cys-239 in ß-tubulin by small molecules as a strategy to promote tubulin heterodimer degradation.

Clinical microtubule-targeting drugs are functionally divided into microtubule-destabilizing and microtubule-stabilizing agents. Drugs from both classes achieve microtubule inhibition by binding different sites on tubulin and inhibiting or promoting polymerization with no concomitant effects on the protein levels of tubulin heterodimers. Here, we have identified a series of small molecules with diverse structures potentially representing a third class of novel tubulin inhibitors that promote degradation by covalent binding to Cys-239 of ß-tubulin. The small molecules highlighted in this study include T0070907 (a peroxisome proliferator-activated receptor γ inhibitor), T007-1 (a T0070907 derivative), T138067, N,N'-ethylene-bis(iodoacetamide) (EBI), and allyl isothiocyanate (AITC). Label-free quantitative proteomic analysis revealed that T007-1 promotes tubulin degradation with high selectivity. Mass spectrometry findings showed covalent binding of both T0070907 and T007-01 to Cys-239 of ß-tubulin. Furthermore, T007-1 exerted a degradative effect on tubulin isoforms possessing Cys-239 (ß2, ß4, and ß5(ß)) but not those containing Ser-239 (ß3, ß6) or mutant ß-tubulin with a C239S substitution. Three small molecules (T138067, EBI, and AITC) also reported to bind covalently to Cys-239 of ß-tubulin similarly induced tubulin degradation. Our results strongly suggest that covalent modification of Cys-239 of ß-tubulin by small molecules could serve as a novel strategy to promote tubulin heterodimer degradation. We propose that these small molecules represent a third novel class of tubulin inhibitor agents that exert their effects through degradation activity.

The seasonal development dynamics of the yak hair cycle transcriptome.

BACKGROUND: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicles (HFs) cells during development are still unknown. Here, using time series data for transcriptome and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HFs development and cycling. RESULTS: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. According to clustering analysis, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters. In the anagen, genes involved in activating hair follicle growth are highly expressed, such as the WNT pathway, FGF pathway, and some genes related to hair follicle differentiation. In the catagen, genes that inhibit differentiation and promote hair follicle cell apoptosis are highly expressed, such as BMP4, and Wise. In the telogen, genes that inhibit hair follicle activity are highly expressed, such as DKK1 and BMP1. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones, such as SLF2, BOP1 and DPP8. They may play unique roles in hormonal regulation of events associated with the hair cycle. CONCLUSIONS: Our results revealed the expression pattern and molecular mechanisms of the seasonal hair cycle in the yak. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.