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Zhang, M.

Publications and source records attributed to Zhang, M..

At least 361 records · Page 20Linked to original sources

Discovery of Alkenyl Oxindole as a Novel PROTAC Moiety for Targeted Protein Degradation via CRL4DCAF11 Recruitment

Alkenyl oxindoles have been characterized as autophagosome-tethering compounds (ATTECs), which can target mutant huntingtin protein (mHTT) for lysosomal degradation. In order to expand the application of alkenyl oxindoles for targeted protein degradation, we designed and synthesized a series of hetero-bifunctional compounds by conjugating different alkenyl oxindoles with the BRD4 inhibitor JQ1. Through structure-activity relationship study, we successfully developed JQ1-alkenyl oxindole conjugates that potently degrade BRD4. Unexpectedly, we found that these molecules degrade BRD4 through the ubiquitin-proteasome system, rather than the autophagy-lysosomal pathway. Using pooled CRISPR interference (CRISPRi) screening, we revealed that JQ1-alkenyl oxindole conjugates recruit the E3 ubiquitin ligase complex CRL4DCAF11 for substrate degradation. Furthermore, we validated the most potent hetero-bifunctional molecule HL435 as a promising drug-like lead compound to exert antitumor activity both in vitro and in vivo. Our research provides new employable PROTAC moieties for targeted protein degradation, providing new possibilities for drug discovery.

biochemistry↗

A self-adaptive and versatile tool for eliminating multiple undesirable variations from transcriptome

Accurate identification of true biological signals from diverse undesirable variations in large-scale transcriptomes is essential for downstream discoveries. Herein, we develop a universal deep neural network, called DeepAdapter, to eliminate various undesirable variations from transcriptomic data. The innovation of our approach lies in automatic learning of the corresponding denoising strategies to adapt to different situations. The data-driven strategies are flexible and highly attuned to the transcriptomic data that requires denoising, yielding significant improvement in reducing undesirable variation originating from batches, sequencing platforms, and bio-samples with varied purity beyond manually designed schemes. Comprehensive evaluations across multiple batches, different RNA measurement technologies and heterogeneous bio-samples demonstrate that DeepAdapter can robustly correct diverse undesirable variations and accurately preserve biological signals. Our findings indicate that DeepAdapter can act as a versatile tool for the comprehensive denoising of the large and heterogeneous transcriptome across a wide variety of application scenarios.

bioinformatics↗

SpiDa-MRI, behavioral and (f)MRI data of adults with fear of spiders

Neuroimaging has greatly improved our understanding of phobic mechanisms. To expand on these advancements, we present data on the heterogeneity of neural patterns in spider phobia combined with various psychological dimensions of spider phobia, using spider-relevant stimuli of various intensities. Specifically, we have created a database in which 49 spider-fearful individuals viewed 225 spider-relevant images in the fMRI scanner and performed behavioral avoidance tasks before and after the fMRI scan. For each participant, the database consists of the neuroimaging part, which includes an anatomical scan, 5 passive-viewing and 2 resting-state functional runs in both raw and pre-processed form along with associated quality control reports. Additionally, a behavioral section includes self-report questionnaires and avoidance tasks collected in pre- and post-sessions. The dataset is well suited for investigating neural mechanisms of phobias, brain-behavior correlations, and also contributes to the existing phobic neuroimaging datasets with spider-fearful samples. O_TBL View this table: org.highwire.dtl.DTLVardef@f76a39org.highwire.dtl.DTLVardef@15eeaa2org.highwire.dtl.DTLVardef@7e4f1borg.highwire.dtl.DTLVardef@7b78f1org.highwire.dtl.DTLVardef@413e78_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗

Cortico-spinal Mechanisms of Periphery Neuromodulation induced Analgesia

BackgroundTranscutaneous Electrical Nerve Stimulation (TENS) is widely used for pain management, yet how different parameters--Conventional (high frequency, low intensity) versus Acupuncture-Like (low frequency, high intensity)--modulate pain remains controversial. These modes produce variable analgesic effects, but their underlying brain-spinal mechanisms are unclear. Clarifying these pathways could refine TENS protocols, optimize clinical outcomes, and reduce opioid reliance, highlighting the need for more precise, non-pharmacological approaches to advanced pain care. MethodsThis single-blind, three-arm randomized trial recruited 95 healthy adults (18-30 years) and assigned them (1:1:1) to Conventional TENS, Acupuncture-Like TENS, or sham. Participants underwent a 30-minute TENS intervention on the left forearm (C5-C6 dermatome) with simultaneous brain-spinal fMRI before and after thermal nociceptive stimuli. The primary outcomes were changes in Numeric Rating Scale (NRS) pain scores and brain-spinal BOLD signals. Secondary outcomes included psycho-physiological interaction (PPI) and mediation analyses of periaqueductal gray (PAG) activity and brain- cord connectivity. FindingsBoth TENS modes significantly reduced pain but engaged distinct cortico-spinal pathways. Conventional TENS yielded local analgesia via dlPAG-driven spinal inhibition plus partial cortical involvement (PAG-vmPFC). By contrast, Acupuncture-Like TENS produced diffuse analgesia through vlPAG-linked top-down modulation reliant on spinal gating. Correlation and mediation analyses confirmed that Conventional TENS integrates spinal and cortical synergies, whereas Acupuncture-Like TENS is dominated by robust descending control. InterpretationDifferent TENS parameters yield distinct analgesic mechanisms. Conventional TENS couples direct spinal inhibition with partial cortical regulation, while Acupuncture-Like TENS relies heavily on top-down pathways passing through the spinal cord. Recognizing these unique descending networks can guide targeted TENS protocols for diverse pain conditions, optimizing clinical outcomes and reducing reliance on pharmacological approaches. FundingsThis work was supported by the National Key R&D Program of China (2022YFC3500603), the National Natural Science Foundation of China (32071061, 82072010, 82030121 and 32100861, 82330057), the Beijing Natural Science Foundation (IS23108, JQ22018).

neuroscience↗

Elucidating the Role of Primary and Secondary Sphere Zn2+ Ligands in the Cyanobacterial CO2 Uptake Complex NDH-14: The Essentiality of Arginine in Zinc Coordination and Catalysis

The uptake of inorganic carbon in cyanobacteria is facilitated by an energetically intensive CO2-concentrating mechanism (CCM). Specialized Type-1 NDH complexes function as a part of this mechanism to couple photosynthetic energy generated by redox reactions of the electron transport chain (ETC) to CO2 hydration. This active site of CO2 hydration incorporates an arginine side chain as a Zn ligand, diverging from the typical histidine and/or cysteine residues found in standard CAs. In this study, we focused on mutating three amino acids in the active site of the constitutively expressed NDH-14 CO2 hydration complex in Synechococcus sp. PCC7942: CupB-R91, which acts as a zinc ligand, and CupB-E95 and CupB-H89, both of which are in close interaction with the arginine ligand. These mutations aimed to explore how they affect the unusual metal ligation by CupB-R91 and potentially influence the unusual catalytic process. The most severe defects in activity among the targeted residues are due to a substitution of CupB-R91 and the ionically interacting E95 since both proved essential for the structural stability of the CupB protein. On the other hand, CupB-H89 mutations show a range of catalytic phenotypes indicating a role of this residue in the catalytic mechanism of CO2-hydration, but no evidence was obtained for aberrant carbonic anhydrase activity that would have indicated uncoupling of the CO2-hydration activity from proton pumping. The results are discussed in terms of possible alternative CO2 hydration mechanisms.

biochemistry↗

Energy Optimization Induces Predictive-coding Properties in a Multicompartment Spiking Neural Network Model

AO_SCPLOWBSTRACTC_SCPLOWPredictive coding is a prominent theoretical framework for understanding the hierarchical sensory processing in the brain, yet how it could be implemented in networks of cortical neurons is still unclear. While most existing works have taken a hand-wiring approach to creating microcircuits that match experimental results, recent work in applying an optimisation approach to rate-based artificial neural networks revealed that cortical connectivity might result from self-organisation given some fundamental computational principle, such as energy efficiency. As no corresponding approach has studied this in more plausible networks of spiking neurons, we here investigate whether predictive coding properties in a multi-compartment spiking neural network can emerge from energy optimisation. We find that a model trained with an energy objective in addition to a task-relevant objective is able to reconstruct internal representations given top-down expectation signals alone. Additionally, neurons in the energy-optimised model also show differential responses to expected versus unexpected stimuli, qualitatively similar to experimental evidence for predictive coding. These findings indicate that predictive-coding-like behaviour might be an emergent property of energy optimisation, providing a new perspective on how predictive coding could be achieved in the cortex.

neuroscience↗

The Role of Rhizosphere Microorganisms and CNPS Genes in Shaping Nutritional Traits of Capsicum

The rhizosphere microbiota plays crucial roles in biogeochemical cycling and primary production. However, there is a lack of research exploring the complex relationships between microbiota and their functional traits in pepper rhizospheres, as well as their impact on nutrient cycling processes. Here, we investigated the effects of pepper species on the rhizomicrobiota and functional genes (C/N/P/S) on nutrient absorptions and accumulations in pepper organs. The results revealed that Pepper YZ/BE had higher N content in all compartments, which could be attributed to the presence of enriched N-metabolic microbes (Gaiellales/Leifsonia) and higher expression of N availability-promoting genes (ureC/amoA2/nxrA/napA) in rhizospheres. Additionally, we utilized co-occurrence network analysis and partial least squares path modeling (PLS-PM) to understand the interactions among the variables. The bacterial network exhibited more associations than the fungal network, and the abundance of certain modules positively correlated with the expression of CNPS genes, which thus significantly influenced pepper nutrient content. The PLS-PM analysis demonstrated that taxa abundance in network modules, functional genes, and rhizospheric soil properties collectively explained 92% of the variance in pepper nutrient content. Overall, this study provides valuable experimental and theoretical insights into the effects of rhizosphere microorganisms and CNPS genes on the nutritional traits of Capsicum. HighlightThe rizho-bacterial community harbored more robust relationships than the fungal ones, which formed the functional clusters highly linking to the below- and aboveground nutrient properties of pepper species.

microbiology↗

PbrSYP71 regulates ER accumulation by interacting with actin during pollen tube growth in Pyrus

The uneven distribution of endoplasmic reticulum (ER) underlies the rapid polar growth of pollen tubes. However, the mechanism governing ER distribution remains elusive. In this study, we have identified a pollen tube-specific syntaxin protein, PbrSYP71. Our findings reveal that both overexpression and knocking down of PbrSYP71 inhibited pollen tube growth. Subcellular localization analysis demonstrates that PbrSYP71 anchors to the ER via its transmembrane structure. Overexpression of PbrSYP71 leads to clustered ER distribution in the pollen tube, while knocking down of PbrSYP71 abolishes the uneven ER distribution. Remarkably, transient overexpression of PbrSYP71{Delta}ABD, lacking the actin binding domain (ABD) of PbrSYP71, has no impact on ER distribution or pollen tube growth. Further investigation indicates that ABD is positioned on F-actin in the pollen tube and has a direct interaction with F-actin. PbrSYP71 assists the ER in moving towards the apex of pollen tube, with ABD displaying autonomous mobility. Our study elucidates that PbrSYP71 maintains uneven distribution of the ER by tethering ER to F-actin, facilitating ER movement towards the pollen tube apex for pear pollen tube elongation. These insights shed light on the mechanisms governing ER distribution in polarized cell growth.

cell biology↗

Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water

The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day-1) and TGEV (0.65 day-1); while in phosphate buffer, HCoV-OC43 (0.51 day-1) had a larger decay rate constant than MHV (0.28 day-1) and TGEV (0.24 day-1). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg-1 min-1 L, followed by MHV (81.33 mg-1 min-1 L) and HCoV-OC43 (59.42 mg-1 min-1 L). ImportanceThis study addresses an important knowledge gap on enveloped virus persistence and disinfection in water. Results have immediate practical applications for shaping evidence-based water policies, particularly in the development of disinfection strategies for pathogenic virus control.

microbiology↗

A Wireless Wearable Ecosystem for Social Network Analysis in Free-living Animals

Understanding the dynamics of animal social systems requires studying variation in contact and interaction, which is influenced by environmental conditions, resource availability, and predation risk, among other factors. Traditional (direct) observational methods have limitations, but advancements in sensor technologies and data analytics provide unprecedented opportunities to study these complex systems in naturalistic environments. Proximity logging and tracking devices, capturing movement, temperature, and social interactions, offer non-invasive means to quantify behavior and develop empirical models of animal social networks. However, challenges remain in integrating different data types, incorporating more sensor modalities, and addressing logistical constraints. To address these gaps, we developed a wireless wearable sensor system with novel features (called "Juxta"), including modular battery packs, memory management for combining data types, reconfigurable deployment modes, and a smartphone app for data collection. We present data from a pilot study on prairie voles (Microtus ochrogaster), which is a small mammal species that exhibits relatively complex social behavior. We demonstrate the potential for Juxta to increase our understanding of the social networks and behavior of free-living animals. Additionally, we propose a framework to guide future research in merging temporal, spatial, and event-driven data. By leveraging wireless technology, battery efficiency, and smart sensing modalities, our wearable ecosystem offers a scalable solution for real-time, high-resolution data capture and analysis in animal social network studies, opening new avenues for exploring complex social dynamics across species and environments.

animal behavior and cognition↗

Tcf12 controls dynamic calvarial bone growth and motor learning in mice

Heterozygous loss-of-function mutations of TCF12 and TWIST1 can each cause craniosynostosis and neurodevelopmental delay in humans. Twist1-Tcf12 interaction plays an important role in regulating suture development. Although the molecular and cellular mechanisms underlying craniosynostosis and neurocognitive dysfunctions in Twist1+/- mice have been studied, less information on the role of Tcf12 in these defects is available. To investigate the functional mechanism of Tcf12 in regulating skull and brain development, we analyzed the skull shape of Wnt1-Cre;Mesp1-Cre;Tcf12fl/fl mice and found that, despite mild coronal synostosis, their skull shape appears to be similar to that of controls. We also found evidence of impaired motor learning ability in Tcf12 mutant mice. Furthermore, loss of Tcf12 in neural crest lineage leads to upregulated Runx2 expression in the calvarial mesenchyme and posterior expansion of the frontal bone in Wnt1-Cre;Tcf12fl/fl mice. Mechanistically, we show that Lmx1b is a direct downstream target of Tcf12 for the regulation of osteogenic differentiation in the calvarial mesenchyme during embryonic development. Importantly, overexpression of Lmx1b inhibits osteogenic differentiation in the calvarial mesenchyme of Wnt1-Cre;Tcf12fl/fl mice, indicating Tcf12s regulation of Lmx1b expression is crucial for controlling osteogenesis during calvarial bone development. Our study suggests that Tcf12 expression in the brain is crucial for motor learning. Moreover, this study establishes a new molecular mechanism underlying regulation of calvarial bone formation. Author SummaryCraniosynostosis is characterized by premature fusion of cranial sutures and associated with abnormal skull growth, delayed brain development, and often impaired brain functions. Loss-of-function mutation of TCF12 can cause coronal synostosis and neurodevelopmental delay in humans. In developing mouse sutures, Tcf12 is essential for maintaining the boundary between sutural and osteogenic cells. However, roles of Tcf12 in skull formation and brain development have not been fully investigated. In this study, we show that loss of Tcf12 leads to brain abnormalities even in the absence of coronal synostosis and that frontal bone expansion results from upregulated osteogenic differentiation in the calvarial mesenchyme in mice. Furthermore, we identify Lmx1b as a downstream target of Tcf12 for the regulation of osteogenic differentiation in the calvarial mesenchyme during frontal bone development. Our findings highlight the role of Tcf12 in the development of calvarial bones and provide new insight into molecular mechanisms for regulation of calvarial bone formation.

developmental biology↗

Arf GTPase-activating protein ASAP1 specifically binds to 440-kD ankyrin-B

The 440-kD giant ankyrin-B (gAnkB) exclusively localizes to axons and is essential for axon development. However, proteins that specifically bind to gAnkB but not to other isoforms of ankyrins are poorly understood. Here, we discovered that an Arf GTPase-activating protein ASAP1 and ASAP2 specifically binds to a short and disordered sequence unique to gAnkB. Biochemical studies showed that the SH3 domain of ASAP1 binds to a 12-residue, positively charged peptide fragment from gAnkB. The high-resolution structure of the ASAP1-SH3 domain in complex with the gAnkB peptide revealed the mechanism underlying this non-canonical SH3 domain-mediated target recognition. Further structural and bioinformatic analysis revealed additional previously unknown ASAP1-SH3 binding partners including Clasp1 and Clasp2, both of which are well-known microtubule regulators. Among all known ASAP1-SH3 binders including those identified in the current study, gAnkB has the strongest affinity in binding to ASAP1. Our results suggest that ASAP1 may function together with gAnkB in regulating axonal cytoskeletons.

biophysics↗

Dynamic parallel transmit diffusion MRI at 7T

Diffusion MRI (dMRI) is inherently limited by SNR. Scanning at 7T increases intrinsic SNR but 7T MRI scans suffer from regions of signal dropout, especially in the temporal lobes and cerebellum. We applied dynamic parallel transmit (pTx) to allow whole-brain 7T dMRI and compared with circularly polarized (CP) pulses in 6 subjects. Subject-specific 2-spoke dynamic pTx pulses were designed offline for 8 slabs covering the brain. We used vendor-provided B0 and B1+ mapping. Spokes positions were set using the Fourier difference approach, and RF coefficients optimized with a Jacobi-matrix high-flip-angle optimizer. Diffusion data were analyzed with FSL. Comparing whole-brain averages for pTx against CP scans: mean flip angle error improved by 15% for excitation (2-spoke-VERSE 15.7{degrees} vs CP 18.4{degrees}, P=0.012) and improved by 14% for refocusing (2-spoke-VERSE 39.7{degrees} vs CP 46.2{degrees}, P=0.008). Computed spin-echo signal standard deviation improved by 14% (2-spoke-VERSE 0.185 vs 0.214 CP, P=0.025). Temporal SNR increased by 5.4% (2-spoke-VERSE 8.47 vs CP 8.04, P=0.004) especially in the inferior temporal lobes. Diffusion fitting uncertainty decreased by 6.2% for first fibres (2-spoke VERSE 0.0655 vs CP 0.0703, P<0.001) and 1.3% for second fibers (2-spoke VERSE 0.139 vs CP 0.141, P=0.01). In conclusion, dynamic parallel transmit improves the uniformity of 7T diffusion-weighted imaging. In future, less restrictive SAR limits for parallel transmit scans are expected to allow further improvements.

neuroscience↗

Decoding of resting-state using task-based multivariate pattern analysis supports the Incentive-Sensitization Theory in nicotine use disorder

BackgroundThe Incentive-Sensitization Theory postulates that addiction is primarily driven by the sensitization of the brains reward system to addictive substances, such as nicotine. According to this theory, exposure to such substances leads to an increase in wanting, while liking the experience remains relatively unchanged. Although this candidate mechanism has been well substantiated through animal brain research, its translational validity for humans has only been partially demonstrated so far, with evidence from human neuroscience data being very limited. MethodsFrom fMRI data of N=31 individuals with Nicotine Use Disorder, we created multivoxel patterns capable of capturing wanting and liking-related dimensions from a smoking cue-reactivity task. Using these patterns, we then designed a novel resting-state reading method to evaluate how much wanting or liking still persist as a neural trace after watching the cues. ResultsWe found that the persistence of wanting-related brain patterns at rest increases with longer smoking history but this was not the case for liking-related patterns. Interestingly, such behavior has not been observed for non-temporal measures of smoking intensity. ConclusionThis study provides basic human neuroscience evidence that the dissociation between liking and wanting escalates over time, further substantiating the Incentive-Sensitization Theory, at least for Nicotine Use Disorder. These results suggest that treatment approaches could be personalized to account for the variability in individuals neural adaptation to addiction by considering how individuals differ in the extent to which their incentive salience system is sensitized.

neuroscience↗

Amygdala habituation during exposure is associated with failure to reduce phobic symptoms

Exposure therapy is an established treatment for anxiety disorders but the mechanisms underpinning its effectiveness remain unclear. Two theories offer contrasting perspectives: the traditional habituation model posits that a form of stimulus desensitization is required during exposure, while the inhibitory learning model emphasizes the formation of new non-fearful associations. Crucially, while the former may manifest as amygdala habituation, the latter may not. To distinguish between the two models, this study uses functional magnetic resonance imaging to examine the amygdala responses of spider-fearful participants during fear exposure. We hypothesized that intervention success might align with stable or even increased amygdala activation - an indicator of active engagement and re-learning as proposed by the inhibitory learning model. Conversely, decreasing amygdala activity might not be a sign of reduced fear memory as proposed by the habituation model, but could signal mental detachment, leading to suboptimal treatment outcomes. Our results corroborated our hypotheses: individuals with escalating amygdala responses during exposure exhibited better clinical progress, while those showing amygdala habituation benefited less. Our results strengthen the case for the inhibitory learning model and highlight that therapy may not aim to diminish fear per se but rather to engage patients in active processing and association formation.

neuroscience↗

An Efficient and Safe Trans-complementation System of Mpox Virus Reproduces Authentic Viral Architecture and Infection

Since the Mpox virus (MPXV) outbreak in 2022, there have been 97,745 cases and 203 fatalities. This outbreak features increased transmission efficiency and a higher infection rate in the MSM population, with the underlying causes remaining unknown. The requirement of BSL-3 laboratories poses a barrier to MPXV research and antiviral development. Here, we report an efficient and safe trans-complementary system that produces a single-round infectious MPXV, preserving the viruss authentic architecture and enabling it to complete its life cycle in complementing cells. This deficient MPXV genome, lacking two essential genes crucial for late gene transcription and viral assembly, is restricted to a single-round infection in non-complementing cell lines. Notably, SCID mice inoculated with this deficient MPXV exhibited no detectable disease or viral load. This deficient MPXV platform has demonstrated its capacity to study innate immunity and cell death during infection in complementing cells. It can also be used for antibody neutralization assays and anti-MPXV drug evaluation. This trans-complementation platform, safe for use in low-biosafety laboratories, offers a valuable resource for MPXV research and countermeasure development.

microbiology↗

Prediction of Carbon Emissions in Guizhou Province-Based on Different Neural Network Models

Global warming caused by greenhouse gas emissions has become a major challenge facing people all over the world. The study of regional human activities and their impacts on carbon emissions is of great significance to achieve the ambitious goal of carbon neutrality and sustainable economic development. Guizhou Province is a typical karst area in China, and its energy consumption is mainly based on fossil fuels.Therefore, it is necessary to predict and analyze its carbon emissions. In this paper, BP neural network and extreme learning machine (ELM) model, which have the advantage of nonlinear processing, will be used to predict the carbon emissions of Guizhou Province from 2020 to 2040. Based on the energy consumption data of Guizhou Province, the carbon emissions of Guizhou Province are calculated by using the conversion method and the inventory compilation method. The data show that the carbon emissions of Guizhou Province show an "S" growth trend; In this paper, 12 influencing factors of carbon emissions are selected, and five influencing factors with larger correlation are screened out by using grey correlation analysis method, and the prediction model of carbon emissions in Guizhou Province is established and simulated, and the prediction performance of BP neural network, ELM and WOA-ELM are compared respectively. Compared with ELM model and BP neural network model, the prediction accuracy of WOA-ELM model is higher; Finally, three development scenarios of carbon emissions are set by scenario analysis, which are baseline scenario, high-speed scenario and low-carbon scenario. On this basis, the size and time of peak carbon emissions in Liaoning Province from 2020 to 2040 are predicted based on WOA-ELM model. The results show that the peak value of carbon dioxide in the low carbon scenario is up to 0.98 million tons 31294 in 2033, the peak value of carbon emissions in the high speed scenario is up to 0.37 million tons 30251 in 2036, and the peak value of carbon emissions in the baseline scenario is up to 0.61 million tons 26243 in 2038. Based on the peak time and prediction results of carbon emissions under the three scenarios, the main factors contributing to the reduction of carbon emissions in Guizhou Province are analyzed, and important data basis is provided for energy conservation and emission reduction in Guizhou Province.

ecology↗

A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence

The planarian Schmidtea mediterranea can regenerate its entire body from small tissue fragments and is studied as regeneration model species. The assembly and functional analysis of planarian genomes has proven challenging due its high A/T content (70% A/T), repetitive nature, and limited transferability of routine laboratory protocols due to their divergent biochemistry. Only few and often fragmented genome assemblies are currently available, and open challenges include the provision of well-annotated chromosome-scale reference assemblies of the model species and other planarians for a comparative genome evolution perspective. Here we report a haplotype-phased, chromosome-scale genome assembly and high-quality gene annotations of the sexual S2 strain of S. mediterranea and provide putative regulatory region annotations via optimized ATAC-seq and ChIP-seq protocols. To additionally leverage sequence conservation for regulatory element annotations, we generated chromosome-scale genome assemblies and chromatin accessibility data for the three closest relatives of S. mediterranea: S. polychroa, S. nova, and S. lugubris. We find substantial divergence in protein-coding sequences and regulatory regions, yet reveal remarkable conservation in ChIP-mark bearing open chromatin regions identified as promoters and enhancers in S. mediterranea. The resulting high-confidence set of evolutionary conserved enhancers and promoters provides a valuable resource for the analysis of gene regulatory circuits and their evolution within the taxon. In addition, our four chromosome-scale genome assemblies provide a first comparative perspective on planarian genome evolution. Our analyses reveal frequent retrotransposon-associated chromosomal inversions and inter-chromosomal translocations that lead to a degradation of synteny across the genus. Interestingly, we further find independent and near-complete losses of the ancestral metazoan synteny across Schmidtea and two other flatworm groups, indicating that platyhelminth genomes largely evolve without syntenic constraints. Our work provides valuable genome resources for the planarian research community and sets a foundation for the comparative genomics of planarians. We reveal a contrast between the fast structural evolution of planarian genomes and the conservation of their regulatory elements, suggesting a unique genome evolution in flatworms where gene positioning may not be essential.

genomics↗