Single-cell analysis of the amphioxus hepatic caecum and vertebrate liver reveals genetic mechanisms of vertebrate liver evolution.

The evolution of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving genetic factors behind it remain unknown. Here we study the evolutionary genetics of liver by comparing the amphioxus hepatic caecum and the vertebrate liver, as well as examining the functional transition within vertebrates. Using in vivo and in vitro experiments, single-cell/nucleus RNA-seq data and gene knockout experiments, we confirm that the amphioxus hepatic caecum and vertebrate liver are homologous organs and show that the emergence of ohnologues from two rounds of whole-genome duplications greatly contributed to the functional complexity of the vertebrate liver. Two ohnologues, kdr and flt4, play an important role in the development of liver sinusoidal endothelial cells. In addition, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with gene duplicates playing a crucial role. We reconstructed the genetic footprint of the transfer of haem detoxification from the liver to the spleen during vertebrate evolution. Together, these findings challenge the previous hypothesis that organ evolution is primarily driven by regulatory elements, underscoring the importance of gene duplicates in the emergence and diversification of a complex organ.

Deciphering the molecular nexus between Omicron infection and acute kidney injury: a bioinformatics approach.

Background: The ongoing global health crisis of COVID-19, and particularly the challenges posed by recurrent infections of the Omicron variant, have significantly strained healthcare systems worldwide. There is a growing body of evidence indicating an increased susceptibility to Omicron infection in patients suffering from Acute Kidney Injury (AKI). However, the intricate molecular interplay between AKI and Omicron variant of COVID-19 remains largely enigmatic. Methods: This study employed a comprehensive analysis of human RNA sequencing (RNA-seq) and microarray datasets to identify differentially expressed genes (DEGs) associated with Omicron infection in the context of AKI. We engaged in functional enrichment assessments, an examination of Protein-Protein Interaction (PPI) networks, and advanced network analysis to elucidate the cellular signaling pathways involved, identify critical hub genes, and determine the relevant controlling transcription factors and microRNAs. Additionally, we explored protein-drug interactions to highlight potential pharmacological interventions. Results: Our investigation revealed significant DEGs and cellular signaling pathways implicated in both Omicron infection and AKI. We identified pivotal hub genes, including EIF2AK2, PLSCR1, GBP1, TNFSF10, C1QB, and BST2, and their associated regulatory transcription factors and microRNAs. Notably, in the murine AKI model, there was a marked reduction in EIF2AK2 expression, in contrast to significant elevations in PLSCR1, C1QB, and BST2. EIF2AK2 exhibited an inverse relationship with the primary AKI mediator, Kim-1, whereas PLSCR1 and C1QB demonstrated strong positive correlations with it. Moreover, we identified potential therapeutic agents such as Suloctidil, Apocarotenal, 3'-Azido-3'-deoxythymidine, among others. Our findings also highlighted a correlation between the identified hub genes and diseases like myocardial ischemia, schizophrenia, and liver cirrhosis. To further validate the credibility of our data, we employed an independent validation dataset to verify the hub genes. Notably, the expression patterns of PLSCR1, GBP1, BST2, and C1QB were consistent with our research findings, reaffirming the reliability of our results. Conclusion: Our bioinformatics analysis has provided initial insights into the shared genetic landscape between Omicron COVID-19 infections and AKI, identifying potential therapeutic targets and drugs. This preliminary investigation lays the foundation for further research, with the hope of contributing to the development of innovative treatment strategies for these complex medical conditions.

A chromosome-level genome of the striated frogfish (Antennarius striatus).

The striated frogfish (Antennarius striatus), a member of the sub-order Antennarioidei within the order Lophiiformes, possesses remarkable adaptations. These include the ability to modulate body coloration for camouflage, utilize bioluminescent esca for predation, and employ elbow-like pectoral fins for terrestrial locomotion, making it a valuable model for studying bioluminescence, adaptive camouflage, fin-to-limb transition, and walking-like behaviors. To better study and contribute to the conservation of the striated frogfish, we obtained the micro-CT image of the pectoral fin bones and generated a high-quality, chromosome-level genome assembly using multiple sequencing technologies. The assembly spans 548.56 Mb with a contig N50 of 21.05 Mb, and 99.35% of the genome is anchored on 24 chromosomes, making it the most complete genome available within Lophiiformes. The genome annotation revealed 28.43% repetitive sequences and 23,945 protein-coding genes. This chromosome-level genome provides valuable genetic resources for frogfish conservation and offers insights into the genetic mechanisms underlying its unique phenotypic evolution. Furthermore, it establishes a foundation for future research on limb development and adaptive camouflage in this species.

Two-dimensional Cu-based materials for electrocatalytic carbon dioxide reduction.

Electrocatalytic CO2 reduction reaction (CO2RR) has emerged as a focal point in sustainable energy research, offering the potential for closed carbon cycle. Among numerous catalysts designed for CO2RR, two-dimensional (2D) Cu-based catalysts stand out for their remarkable performance in efficiently converting CO2 into high-value-added C1 and C2+ chemicals. Herein, we discuss the recent progress and challenges in the realm of CO2RR utilizing 2D Cu-based catalysts. The first section introduces various synthetic strategies, emphasizing the features and advantages of different techniques and proposing solutions to existing challenges. The second part outlines the reaction mechanism underlying the production of C1 and C2+ products on Cu-based catalysts, then summarizes applications of different types 2D Cu-based catalysts in CO2RR. Additionally, we evaluate the limitations of 2D Cu-based catalysts and propose improved strategies. Through this exploration of research advances and challenges, we hope to illuminate the path toward developing excellent CO2 electrocatalysts.

Chromosome-level genome assembly of hadal snailfish reveals mechanisms of deep-sea adaptation in vertebrates.

As the deepest vertebrate in the ocean, the hadal snailfish (Pseudoliparis swirei), which lives at a depth of 6,000-8,000 m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of trimethylamine N-oxide in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep-sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.

HnRNP A2/B1 as a potential anti-tumor target for triptolide based on a simplified thermal proteome profiling method using XGBoost.

BACKGROUND: Triptolide (TP) is a highly active natural medicinal ingredient with significant potential in anticancer. The strong cytotoxicity of this compound suggests that it may have a wide range of targets within cells. However, further target screening is required at this stage. Traditional drug target screening methods can be significantly optimized using artificial intelligence (AI). PURPOSE:  This study aimed to identify the direct protein targets and explain the multitarget action mechanism of the anti-tumor effect of TP with the help of AI. METHODS:  The CCK8, scratch test, and flow cytometry analysis were used to examine cell proliferation, migration, cell cycle, and apoptosis in tumor cells treated with TP in vitro. The anti-tumor effect of TP in vivo was evaluated by constructing a tumor model in nude mice. Furthermore, we established a simplified thermal proteome analysis (TPP) method based on XGBoost (X-TPP) to rapidly screen the direct targets of TP. RESULTS: We validated the effects of TP on protein targets through RNA immunoprecipitation and pathways by qPCR and Western blotting. TP significantly inhibited tumor cell proliferation and migration and promoted apoptosis in vitro. Continuous administration of TP to tumor mice can significantly suppress tumor tissue size. We verified that TP can affect the thermal stability of HnRNP A2/B1 and exert anti-tumor effects by inhibiting HnRNP A2/B1-PI3K-AKT pathway. Adding siRNA to silence HnRNP A2/B1 also significantly down-regulated expression of AKT and PI3K. CONCLUSION: The X-TPP method was used to show that TP regulates tumor cell activity through its potential interaction with HnRNP A2/B1.

A population of stem cells with strong regenerative potential discovered in deer antlers.

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene (PRRX1+ mesenchymal cells). We also identified a population of "antler blastema progenitor cells" (ABPCs) that developed from the PRRX1+ mesenchymal cells and directed the antler regeneration process. Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.

Pseudo-chromosome-length genome assembly for a deep-sea eel Ilyophis brunneus sheds light on the deep-sea adaptation.

High hydrostatic pressure, low temperature, and scarce food supply are the major factors that limit the survival of vertebrates in extreme deep-sea environments. Here, we constructed a high-quality genome of the deep-sea Muddy arrowtooth eel (MAE, Ilyophis brunneus, captured below a depth of 3,500 m) by using Illumina, PacBio, and Hi-C sequencing. We compare it against those of shallow-water eel and other outgroups to explore the genetic basis that underlies the adaptive evolution to deep-sea biomes. The MAE genome was estimated to be 1.47 Gb and assembled into 14 pseudo-chromosomes. Phylogenetic analyses indicated that MAE diverged from its closely related shallow-sea species, European eel, ∼111.9 Mya and experienced a rapid evolution. The genome evolutionary analyses primarily revealed the following: (i) under high hydrostatic pressure, the positively selected gene TUBGCP3 and the expanded family MLC1 may improve the cytoskeleton stability; ACOX1 may enhance the fluidity of cell membrane and maintain transport activity; the expansion of ABCC12 gene family may enhance the integrity of DNA; (ii) positively selected HARS likely maintain the transcription ability at low temperatures; and (iii) energy metabolism under a food-limited environment may be increased by expanded and positively selected genes in AMPK and mTOR signaling pathways.

The predictive value of neutrophil to lymphocyte ratio on 30-day outcomes in spontaneous intracerebral hemorrhage patients after surgical treatment: A retrospective analysis of 128 patients.

Objective: The purpose of this study was to explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on 30-day outcomes in patients with spontaneous intracerebral hemorrhage (ICH) after surgical treatment. Methods: This retrospective study utilized data from patients with ICH who underwent craniotomy or minimally invasive puncture and drainage (MIPD) between January 2015 and June 2021. The patients meeting the inclusion criteria were divided into two groups according to 30-day outcomes, namely, the favorable outcome group and the poor outcome group. Sex, age, time from onset to admission, vital signs at admission, admission Glasgow Coma Scale (GCS) score, diabetes mellitus, hypertension, hematoma volume, hematoma location, surgical approach, and NLR at different time points were all recorded and analyzed. Results: A total of 128 patients were finally enrolled in this study, including 32 and 96 patients in the favorable outcome group and the poor outcome group, respectively. During the course of ICH, the changing trend of NLR was to increase first and then decrease and peaked within 48 h after surgery. In the univariate analysis, systolic blood pressure, admission GCS score, hematoma volume, surgical approach, and NLR within 48 h after surgery were statistically significant. In the multivariable analysis, NLR within 48 h after surgery (odds ratio [OR] = 1.342, p < 0.001) was an independent risk factor of the 30-day outcomes in patients with ICH after surgical treatment. The receiver operating characteristic (ROC) analysis showed that the best predictive cut-off value for NLR within 48 h after surgery was 12.35 [sensitivity 82.9%, specificity 81.8%, and area under the curve (AUC) 0.877] and 14.46 (sensitivity 55.1%, specificity 87.5%, and area under the curve 0.731) for the MIPD group and the craniotomy group, respectively. Conclusions: In the process of ICH, the value of NLR was increased first and then decreased and peaked within 48 h after surgery. NLR within 48 h after surgery was an independent risk factor of the 30-day outcomes in patients with ICH. The peak NLR >12.35 or 14.46 in patients receiving MIPD or craniotomy reflected a poor prognosis, respectively.

Quantum Teleportation and Dense Coding in Multiple Bosonic Reservoirs.

The effect of a reservoir on quantum communication depends on its spectral density. The efficiency of quantum teleportation and dense coding is explored when each one of the channel qubits is coupled simultaneously to multiple bosonic reservoirs. It is shown that the non-Markovianity triggered by increasing the reservoir number can induce revivals of quantum advantages of the two protocols after their disappearance. However, the backflow of information to the system that signifies non-Markovianity does not always induce immediate revivals of the quantum advantages. There may be a delayed effect for some initial states, and only as the backflow of information accumulates to a certain extent can the revivals of quantum advantages be triggered.

Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish.

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.

Gender-Disparities in the in-Hospital Clinical Outcome Among Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

PURPOSE: The current study was to evaluate the gender-disparities in the in-hospital thrombotic and bleeding events among patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Patients with CKD undergoing PCI were retrospectively enrolled. Baseline characteristics, and thrombotic and bleeding events occurred during hospitalization were collected and compared by gender. RESULTS: Compared to males (n = 558), females (n = 402) were older and more likely to have diabetes mellitus (37.1% vs 29.7%). Females had a lower estimated glomerular filtration rate (eGFR; 51.2 ± 7.9 vs 54.6 ± 5.1 mL/min/1.73m2) and were more likely to undergo urgent PCI (66.7% vs 60.2%) and use glycoprotein IIb/IIIa inhibitor (15.4% vs 7.5%) at peri-PCI period. Compared to males, females had a higher rate of in-hospital mortality which was due to thrombotic events (9.0% vs 3.4%). Females also had a higher rate of moderate-to-severe hemorrhage (8.0% vs 3.2%). After multivariable adjustment, diabetes mellitus (odds ratio [OR] 1.15 and 95% confidence interval [CI] 1.07-1.29) and acute coronary syndrome (ACS) presentation (OR 1.53 and 95% CI 1.34-1.93) were associated with gender-disparities in composite thrombotic events. Ageing (OR 1.10 and 95% CI 1.02-1.33), diabetes mellitus (OR 1.21 and 95% CI 1.07-1.40) and glycoprotein IIb/IIIa inhibitor use (OR 1.13 and 95% CI 1.02-1.28) were associated with composite bleeding events. CONCLUSION: Females with CKD undergoing PCI had a higher risk of experiencing in-hospital thrombotic and bleeding events than males.

MiR-133a is a potential target for arterial calcification in patients with end-stage renal disease.

BACKGROUND: Arterial calcification is an important risk factor for patients with end-stage renal disease. Despite substantial research efforts, the detailed mechanisms of the process of arterial calcification in end-stage renal disease remain unclear. METHODS: miR-133a expression in radial artery samples was detected by FISH and Alizarin Red Staining. The expressions of miR-133a and RUNX2 in A7r5 cells with BMP2 induction were detected by qRT-PCR. In addition, qRT-PCR, Western blot, and ELISA assay were performed to detect changes in miR-133a levels in A7R5 cells after different treatments. RESULTS: Alizarin Red staining showed that red crystal deposition occurred in the tunica media. FISH analysis indicated that miR-133a was upregulated in the tunica media of the radial artery samples without calcification when compared with those with calcification. We also found that expression of RUNX2 in A7r5 cells increased at day 7 and day 14 after BMP2 induction and decreased miR-133a expression decreased at day 14. In addition, RUNX2 protein and OCN expression were upregulated in A7r5 cells during BMP2-induced calcification. When miR-133a expression was suppressed, cell calcification aggravated, which led to upregulation of RUNX2 and OCN. When miR-133a was overexpressed, calcification of cells was inhibited, resulting in downregulation of RUNX2 and OCN. CONCLUSION: The present study reveals that miR-133a could indirectly regulate cell calcification through the RUNX2 gene expression. Our findings provide insight into the potential use of miR-133a as a molecular target for diagnosing vascular calcification in end-stage renal disease.

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe.

The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.

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.

Interface Engineering of Co-LDH@MOF Heterojunction in Highly Stable and Efficient Oxygen Evolution Reaction.

The electrochemical splitting of water into hydrogen and oxygen is considered one of the most promising approaches to generate clean and sustainable energy. However, the low efficiency of the oxygen evolution reaction (OER) acts as a bottleneck in the water splitting process. Herein, interface engineering heterojunctions between ZIF-67 and layered double hydroxide (LDH) are designed to enhance the catalytic activity of the OER and the stability of Co-LDH. The interface is built by the oxygen (O) of Co-LDH and nitrogen (N) of the 2-methylimidazole ligand in ZIF-67, which modulates the local electronic structure of the catalytic active site. Density functional theory calculations demonstrate that the interfacial interaction can enhance the strength of the Co-Oout bond in Co-LDH, which makes it easier to break the H-Oout bond and results in a lower free energy change in the potential-determining step at the heterointerface in the OER process. Therefore, the Co-LDH@ZIF-67 exhibits superior OER activity with a low overpotential of 187 mV at a current density of 10 mA cm-2 and long-term electrochemical stability for more than 50 h. This finding provides a design direction for improving the catalytic activity of OER.

Propagating multi-channel four-wave mixing process in the modulated moving photonic band gap.

Three and four electromagnetically induced transparency windows generate the multi-channel four-wave mixing (FWM) process are observed in a four-level atomic system. The transmission of the probe field and the reflection of the FWM are investigated in the modulated moving photonic band gap structures which are caused by the coupling fields with a relative small detuning offset when scanning detuning frequency of the probe field and the dressing field, respectively. The experimental results show that the more channels spectrum signal of the FWM process can be modulated and the generated multi-channel can be further modulated by adding a dressing field. We have also explained theoretically these experimental results which may have applications in the design of photonic crystal and optical signal amplifiers.

Synergistic effects of anti-MRSA herbal extracts combined with antibiotics.

MRSA is a super drug-resistant bacterium. Developing new drug or therapeutic strategies against MRSA is urgently needed. Increasing evidence has shown that herbal extracts and antibiotics can have synergistic effects against MRSA. This review focuses on commonly used antibiotics combined with herbal extracts against MRSA and the corresponding mechanisms. Through systematic analysis, we found that herbal extracts combined with antibiotics, such as ß-lactams, quinolones, aminoglycosides, tetracyclines and glycopeptides, could greatly enhance the antibacterial effects of the antibiotics, reduce the dosage and toxic side effects, and reverse MRSA resistance. Therefore, we conclude that herbal extracts combined with antibiotics may be a promising strategy to combat MRSA. This review provides a novel idea for overcoming antibiotic resistance.

High-throughput screening suggests glutathione synthetase as an anti-tumor target of polydatin using human proteome chip.

Polydatin (PD) is a bio-active ingredient with known anti-tumor effects. However, its specific protein targets yet have not been systematically screened, and the molecular anti-tumor mechanism is still unclear. Here, proteomic-chip was efficiently used to screen potential targets of PD. First, we investigated through animal experiment and proteomics studies, and found that polydatin play an important role in tumor cells. Then, the red-green fluorescent of polydatin was compared comprehensively to screen its targets on chip, followed by bioinformatics analysis. Glutathione synthetase (GSS) was selected as candidate research target. After a series of molecular biological experiments GSS was confirmed a target protein for PD in vitro. Moreover, we also found that PD can significantly inhibit the activity of GSS in vitro and live cells. Our findings reveal that PD could be a selective small-molecule GSS enzyme activity inhibitor and GSS could be a potential therapeutic target in cancer.