The Mechanism of Exogenous Salicylic Acid and 6-Benzylaminopurine Regulating the Elongation of Maize Mesocotyl.

The elongation of the mesocotyl plays an important role in the emergence of maize deep-sowing seeds. This study was designed to explore the function of exogenous salicylic acid (SA) and 6-benzylaminopurine (6-BA) in the growth of the maize mesocotyl and to examine its regulatory network. The results showed that the addition of 0.25 mmol/L exogenous SA promoted the elongation of maize mesocotyls under both 3 cm and 15 cm deep-sowing conditions. Conversely, the addition of 10 mg/L exogenous 6-BA inhibited the elongation of maize mesocotyls. Interestingly, the combined treatment of exogenous SA-6-BA also inhibited the elongation of maize mesocotyls. The longitudinal elongation of mesocotyl cells was the main reason affecting the elongation of maize mesocotyls. Transcriptome analysis showed that exogenous SA and 6-BA may interact in the hormone signaling regulatory network of mesocotyl elongation. The differential expression of genes related to auxin (IAA), jasmonic acid (JA), brassinosteroid (BR), cytokinin (CTK) and SA signaling pathways may be related to the regulation of exogenous SA and 6-BA on the growth of mesocotyls. In addition, five candidate genes that may regulate the length of mesocotyls were screened by Weighted Gene Co-Expression Network Analysis (WGCNA). These genes may be involved in the growth of maize mesocotyls through auxin-activated signaling pathways, transmembrane transport, methylation and redox processes. The results enhance our understanding of the plant hormone regulation of mesocotyl growth, which will help to further explore and identify the key genes affecting mesocotyl growth in plant hormone signaling regulatory networks.

Electroacupuncture facilitates vascular normalization by inhibiting Glyoxalase1 in endothelial cells to attenuate glycolysis and angiogenesis in triple-negative breast cancer.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke presents a global health challenge, necessitating an in-depth comprehension of its pathophysiology and therapeutic strategies. While reperfusion therapy salvages brain tissue, it also triggers detrimental cerebral ischemia-reperfusion injury (CIRI). In our investigation, we observed the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in an oxygen-glucose deprivation/reoxygenation (OGD/R) model using HT22 cells (P < 0.05). This activation contributed to oxidative stress (P < 0.05), enhanced autophagy (P < 0.05) and cell death (P < 0.05) during CIRI. Silencing NCOA4 effectively mitigated OGD/R-induced damage (P < 0.05). These findings suggested that targeting NCOA4-mediated ferritinophagy held promise for preventing and treating CIRI. Subsequently, we substantiated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway effectively regulated the NCOA4-mediated ferritinophagy, by applying the cGAS inhibitor RU.521 and performing NCOA4 overexpression (P < 0.05). Suppressing the cGAS-STING pathway efficiently curtailed ferritinophagy (P < 0.05), oxidative stress (P < 0.05), and cell damage (P < 0.05) of CIRI, while NCOA4 overexpression could alleviate this effect (P < 0.05). Finally, we elucidated the specific molecular mechanism underlying the protective effect of the iron chelator deferoxamine (DFO) on CIRI. Our findings revealed that DFO alleviated hypoxia-reoxygenation injury in HT22 cells through inhibiting NCOA4-mediated ferritinophagy and reducing ferrous ion levels (P < 0.05). However, the protective effects of DFO were counteracted by cGAS overexpression (P < 0.05). In summary, our results indicated that the activation of the cGAS-STING pathway intensified cerebral damage during CIRI by inducing NCOA4-mediated ferritinophagy. Administering the iron chelator DFO effectively attenuated NCOA4-induced ferritinophagy, thereby alleviating CIRI. Nevertheless, the role of the cGAS-STING pathway in CIRI regulation likely involves intricate mechanisms, necessitating further validation in subsequent investigations.

Effect of cytochrome P450 3A4 on tissue distribution of humantenmine, koumine, and gelsemine, three alkaloids from the toxic plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5 min after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20 min. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Cholinergic Neuromodulation of Prefrontal Attractor Dynamics Controls Performance in Spatial Working Memory.

The behavioral and neural effects of the endogenous release of acetylcholine following stimulation of the nucleus basalis (NB) of Meynert have been recently examined in two male monkeys (Qi et al., 2021). Counterintuitively, NB stimulation enhanced behavioral performance while broadening neural tuning in the prefrontal cortex (PFC). The mechanism by which a weaker mnemonic neural code could lead to better performance remains unclear. Here, we show that increased neural excitability in a simple continuous bump attractor model can induce broader neural tuning and decrease bump diffusion, provided neural rates are saturated. Increased memory precision in the model overrides memory accuracy, improving overall task performance. Moreover, we show that bump attractor dynamics can account for the nonuniform impact of neuromodulation on distractibility, depending on distractor distance from the target. Finally, we delve into the conditions under which bump attractor tuning and diffusion balance in biologically plausible heterogeneous network models. In these discrete bump attractor networks, we show that reducing spatial correlations or enhancing excitatory transmission can improve memory precision. Altogether, we provide a mechanistic understanding of how cholinergic neuromodulation controls spatial working memory through perturbed attractor dynamics in the PFC.

A system dynamics-based model for the evolution of environmental group events.

Based on the system dynamics theory, this paper establishes an environmental mass event evolution model and explores the evolution law of mass events caused by environmental problems. From a methodological point of view, the mixed-strategy evolutionary game principle and dynamic punishment measures are combined, and simulation analysis is carried out by Anylogic software, and the results show that there is no stable evolutionary equilibrium solution for the two sides of the game in the traditional asymmetric mixed-strategy game model, and after adjusting the game payoff matrix and incorporating the dynamic punishment strategy, stable evolutionary equilibrium solutions appear in the evolutionary game model, and the system begins to tend to be stabilized. The process and conclusions of the simulation experiment provide methodological reference and theoretical support for the analysis of the evolution of environmental mass events.

An ultra-soft conductive elastomer for multifunctional tactile sensors with high range and sensitivity.

Flexible tactile sensors have become important as essential tools for facilitating human and object interactions. However, the materials utilized for the electrodes of capacitive tactile sensors often cannot simultaneously exhibit high conductivity, low modulus, and strong adhesiveness. This limitation restricts their application on flexible interfaces and results in device failure due to mechanical mismatch. Herein, we report an ultra-low modulus, highly conductive, and adhesive elastomer and utilize it to fabricate a microstructure-coupled multifunctional flexible tactile sensor. We prepare a supramolecular conductive composite film (SCCF) as the electrode of the tactile sensor using a supramolecular deep eutectic solvent, polyvinyl alcohol (PVA) solution, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), and MXene suspension. We employ a polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) film containing 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM:TFSI) as the dielectric layer to fabricate capacitive sensors with an electrical double layer structure. Furthermore, we enhance the performance of the device by incorporating coupled pyramid and dome microstructures, which endow the sensor with multi-directional force detection. Our SCCF exhibits extremely high conductivity (reaching 710 S cm-1), ultra-low modulus (0.8 MPa), and excellent interface adhesion strength (>120 J m-2). Additionally, due to the outstanding conductivity and unique structure of the SCCF, it possesses remarkable electromagnetic shielding ability (>50 dB). Moreover, our device demonstrates a high sensitivity of up to 1756 kPa-1 and a wide working range reaching 400 kPa, combining these attributes with the requirements of an ultra-soft human-machine interface to ensure optimal contact between the sensor and interface materials. This innovative and flexible tactile sensor holds great promise and potential for addressing various and complex demands of human-machine interaction.

Cholinergic neuromodulation of prefrontal attractor dynamics controls performance in spatial working memory.

The behavioral and neural effects of the endogenous release of acetylcholine following stimulation of the Nucleus Basalis of Meynert (NB) have been recently examined (Qi et al. 2021). Counterintuitively, NB stimulation enhanced behavioral performance while broadening neural tuning in the prefrontal cortex (PFC). The mechanism by which a weaker mnemonic neural code could lead to better performance remains unclear. Here, we show that increased neural excitability in a simple continuous bump attractor model can induce broader neural tuning and decrease bump diffusion, provided neural rates are saturated. Increased memory precision in the model overrides memory accuracy, improving overall task performance. Moreover, we show that bump attractor dynamics can account for the nonuniform impact of neuromodulation on distractibility, depending on distractor distance from the target. Finally, we delve into the conditions under which bump attractor tuning and diffusion balance in biologically plausible heterogeneous network models. In these discrete bump attractor networks, we show that reducing spatial correlations or enhancing excitatory transmission can improve memory precision. Altogether, we provide a mechanistic understanding of how cholinergic neuromodulation controls spatial working memory through perturbed attractor dynamics in PFC.

Bioinspired electrically stable, optically tunable thermal management electronic skin via interfacial self-assembly.

The skin is the largest organ in the human body and serves vital functions such as sensation, thermal management, and protection. While electronic skin (E-skin) has made significant progress in sensory functions, achieving adaptive thermal management akin to human skin has remained a challenge. Drawing inspiration from squid skin, we have developed a hybrid electronic-photonic skin (hEP-skin) using an elastomer semi-embedded with aligned silver nanowires through interfacial self-assembly. With mechanically adjustable optical properties, the hEP-skin demonstrates adaptive thermal management abilities, warming in the range of +3.5°C for heat preservation and cooling in the range of -4.2°C for passive cooling. Furthermore, it exhibits an ultra-stable high electrical conductivity of âˆ¼4.5×104 S/cm, even under stretching, bending or torsional deformations over 10,000 cycles. As a proof of demonstration, the hEP-skin successfully integrates stretchable light-emitting electronic skin with adaptive thermal management photonic skin.

Cadmium Exposure Induces Apoptosis and Necrosis of Thyroid Cells via the Regulation of miR-494-3p/PTEN Axis.

Cadmium (Cd) exposure is a persistent pollution problem, necessitating caution in using cadmium-expelling complexing agents. Currently, there is no targeted therapy to treat Cd poisoning. The thyroid gland is a major endocrine organ that directly regulates thyroid hormones involved in various physiological processes and is a target organ for Cd accumulation. Herein, the effects of Cd exposure on swine thyroid glands were investigated. Six-week-old male pigs were randomly divided into the Cd and control groups. The control group was fed a normal diet containing 0 mg Cd/kg, while the Cd group was fed a diet containing 20 mg Cd/kg (CdCl2) for 40 days. The regulation mechanism of phosphatase and tensin homolog (PTEN) microRNA-494-3p (miR-494-3p) was evaluated to determine the toxic effects of Cd exposure on free radicals' cleaner. Notably, heat shock proteins (HSPs) were triggered as defense agents against Cd. Cd exposure increased the enzyme activity of superoxide dismutase1(SOD1) and SOD2, catalase (CAT), and glutathione (GSH), and the endoplasmic reticulum stress in thyroid cells. Histopathological staining, RT-qPCR, and Western Blot assays were further employed to detect possible apoptosis and necroptosis of thyroid cells induced by Cd exposure. The assays revealed increased thyroid inflammatory injury, fibrosis, and apoptosis caused by Cd exposure. This study demonstrates the role of microRNAs in regulating Cd toxicity in pig thyroid tissue and provides evidence of Cd's negative effects. It further provides an assessment of the toxicological impact of Cd as an environmental endocrine disruptor (ED) that threatens public health and safety, which forms a basis for the development of Cd poisoning treatment therapies.

A comprehensive assessment of external exposure to persistent halogenated organic pollutants for residents in an e-waste recycling site, South China.

Human skin wipes from 30 participants, air, dust, and food items were collected from a former electronic waste site in South China to provide a comprehensive understanding of residents' exposure to halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs). The total concentration of halogenated organic pollutants (HOPs) in the dust, air, food and skin wipes ranged 240-25000 ng/g, 130-2500 pg/m3, 0.08-590 ng/g wet weight, and 69-28000 ng/m2, respectively. Wild fish, vegetables, and air were dominated by PCBs, whereas dust, livestock, and poultry were dominated by HFRs. The HOP concentrations were several orders of magnitude higher in local foodstuffs than in market foodstuffs. The chemical composition on the forehead was remarkably different from that on the hand. The importance of different exposure routes depends on the residents' food choices, except decabromodiphenyl ethane (DBDPE). For residents who consumed a 100-foot diet (mainly egg) and local wild fish, diet ingestion overwhelmed other exposure routes, and PCBs were mainly contributed by fish and HFRs by egg. For residents who consumed market food, the dermal absorption of most PCB congeners and dust ingestion of highly brominated flame retardants were relatively prominent. Inhalation was found to be a crucial route for pentabromoethylbenzene (PBEB).

Training-Dependent Gradients of Timescales of Neural Dynamics in the Primate Prefrontal Cortex and Their Contributions to Working Memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, for example, from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales are inherent properties of neurons and/or depend on training in a specific task and if the latter, how their modulations contribute to task performance. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.

ALKBH5 Stabilized N6-Methyladenosine-Modified LOC4191 to Suppress E. coli-Induced Apoptosis.

E. coli is a ubiquitous pathogen that is responsible for over one million fatalities worldwide on an annual basis. In animals, E. coli can cause a variety of diseases, including mastitis in dairy cattle, which represents a potential public health hazard. However, the pathophysiology of E. coli remains unclear. We found that E. coli could induce global upregulation of m6A methylation and cause serious apoptosis in bovine mammary epithelial cells (MAC-T cells). Furthermore, numerous m6A-modified lncRNAs were identified through MeRIP-seq. Interestingly, we found that the expression of LOC4191 with hypomethylation increased in MAC-T cells upon E. coli-induced apoptosis. Knocking down LOC4191 promoted E. coli-induced apoptosis and ROS levels through the caspase 3-PARP pathway. Meanwhile, knocking down ALKBH5 resulted in the promotion of apoptosis through upregulated ROS and arrested the cell cycle in MAC-T cells. ALKBH5 silencing accelerated LOC4191 decay by upregulating its m6A modification level, and the process was recognized by hnRNP A1. Therefore, this indicates that ALKBH5 stabilizes m6A-modified LOC4191 to suppress E. coli-induced apoptosis. This report discusses an initial investigation into the mechanism of m6A-modified lncRNA in cells under E. coli-induced apoptosis and provides novel insights into infectious diseases.

Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis.

OBJECTIVE: Platelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial. This meta-analysis was carried out to evaluate the prognostic values of PLR in patients with BC treated with neoadjuvant chemotherapy (NACT). DESIGN: Meta-analysis. DATA SOURCES: Relevant literature published on the following databases: PubMed, Embase, Web of Science databases and the Cochrane Library. ELIGIBILITY CRITERIA: All studies involving patients with BC treated with NACT and peripheral blood pretreatment PLR recorded were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted and evaluated HR/OR and its 95% CI of survival outcomes, pathological complete response (pCR) rate and clinicopathological parameters. RESULTS: The last search was updated to 31 December 2022. A total of 22 studies with 5533 patients with BC treated with NACT were enrolled in the final meta-analysis. Our results demonstrate that elevated PLR value appears to correlate with low pCR rate (HR 0.77, 95% CI 0.67 to 0.88, p<0.001, I2=75.80%, Ph<0.001) and poor prognosis, including overall survival (OS) (HR 1.90, 95% CI 1.39 to 2.59, p<0.001; I2=7.40%, Ph=0.365) and disease-free survival (HR 1.97, 95% CI 1.56 to 2.50, p<0.001; I2=0.0%, Ph=0.460). Furthermore, PLR level was associated with age (OR 0.86, 95% CI 0.79 to 0.93, p<0.001, I2=40.60%, Ph=0.096), menopausal status (OR 0.83, 95% CI 0.76 to 0.90, p<0.001, I2=50.80%, Ph=0.087) and T stage (OR 1.05, 95% CI 1.00 to 1.11, p=0.035; I2=70.30%, Ph=0.005) of patients with BC. CONCLUSIONS: This meta-analysis demonstrated that high PLR was significantly related to the low pCR rate, poor OS and disease-free survival (DFS) of patients with BC treated with NACT. Therefore, PLR can be used as a potential predictor biomarker for the efficacy of NACT in BC.

Genetic and cultural adaptations underlie the establishment of dairy pastoralism in the Tibetan Plateau.

BACKGROUND: Domestication and introduction of dairy animals facilitated the permanent human occupation of the Tibetan Plateau. Yet the history of dairy pastoralism in the Tibetan Plateau remains poorly understood. Little is known how Tibetans adapted to milk and dairy products. RESULTS: We integrated archeological evidence and genetic analysis to show the picture that the dairy ruminants, together with dogs, were introduced from West Eurasia into the Tibetan Plateau since ~ 3600 years ago. The genetic admixture between the exotic and indigenous dogs enriched the candidate lactase persistence (LP) allele 10974A > G of West Eurasian origin in Tibetan dogs. In vitro experiments demonstrate that - 13838G > A functions as a LP allele in Tibetans. Unlike multiple LP alleles presenting selective signatures in West Eurasians and South Asians, the de novo origin of Tibetan-specific LP allele - 13838G > A with low frequency (~ 6-7%) and absence of selection corresponds - 13910C > T in pastoralists across eastern Eurasia steppe. CONCLUSIONS: Results depict a novel scenario of genetic and cultural adaptations to diet and expand current understanding of the establishment of dairy pastoralism in the Tibetan Plateau.

Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.

A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and ßGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted ßGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.

Optical heating-induced spectral tuning of supercontinuum generation in liquid core fibers using multiwall carbon nanotubes.

In this work, we demonstrate the optical heating modulation of soliton-based supercontinuum generation through the employment of multi-walled carbon nanotubes (MW-CNTs) acting as fast and efficient heat generators. By utilizing highly dispersion-sensitive liquid-core fibers in combination with MW-CNTs coated to the outer wall of the fiber, spectral tuning of dispersive waves with response times below one second via exploiting the strong thermo-optic response of the core liquid was achieved. Local illumination of the MW-CNTs coated fiber at selected points allowed modulation of the waveguide dispersion, thus controlling the soliton fission process. Experimentally, a spectral shift of the two dispersive waves towards the region of anomalous dispersion was observed at increasing temperatures. The presented tuning concept shows great potential in the context of nonlinear photonics, as complex and dynamically reconfigurable dispersion profiles can be generated by using structured light fields. This allows investigating nonlinear frequency conversion processes under unconventional conditions, and realizing nonlinear light sources that are reconfigurable quickly.

Antinociceptive effect of gelsenicine, principal toxic alkaloids of gelsemium, on prostaglandin E2-induced hyperalgesia in mice: Comparison with gelsemine and koumine.

Gelsemium elegans (G.elegans) is a plant of the Loganiaceae family, known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 µg/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyRα3 and Gephyrin. The PGE2 model group showed decreased expression levels of GlyRα3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE2-induced hyperalgesia by upregulating the expression of GlyRα3 and Gephyrin, which are key targets of the Gly receptor pathway.

Linking PAHs concentration, risk to PAHs source shift in soil and water in epikarst spring systems, Southwest China.

A systematic assessment of the variations in the ecological risk of PAHs and the key emission sources controlling the variations is of great importance to human health and aquatic organisms. PAH concentrations, composition, source, and ecological risk in soils and water in two different periods (2010-2011 and 2019) of three typical epikarst springs in Southwest China were investigated. Results showed that PAH concentrations in soil and water have an overall downward trend (a reduction of 57 % and 93 %, respectively) in the past 10 years, which is consistent with the downward trend in the relative contribution rate of raw coal production (a 66 % reduction). In terms of composition, the proportion of low-ring PAHs decreased, medium-ring and high-ring PAHs increased in the soil profile. The proportion of low-ring PAHs did not change obviously, the proportion of medium-ring PAHs increased, and the proportion of high-ring PAHs decreased in epikarst springs. The source of PAHs changed remarkably over time, the relative contribution of coal combustion to PAHs decreased from 38 % to 20 %, and the vehicle contribution of PAHs increased from 31 % to 44 % in soils. The relative contribution rate of unburned oil and coke oven and biomass combustion change is less. Furthermore, the ecological risk of PAHs in the soils was reduced from moderate risk 2 to moderate risk 1, the risk in epikarst spring was reduced from high risk to moderate risk 2 after 10 years. This study demonstrates that substituting petroleum and coal with green energies can reduce PAH concentrations and risk.

Training-dependent gradients of timescales of neural dynamics in the primate prefrontal cortex and their contributions to working memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, e.g., from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales depend on training in a specific task and/or are an inherent property of neurons, and whether more fine-grained hierarchies of timescales exist within specific cortical regions. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition. Significance statement: Recent studies have demonstrated that neural responses exhibit dynamics with different timescales that follow a certain order or hierarchy across cortical areas. While the hierarchy of timescales is consistent across different tasks, it is unknown if these timescales emerge only after training or if they represent inherent properties of neurons. To answer this question, we estimated multiple timescales in neural response across five subregions of the monkeys' lateral prefrontal cortex before and after training on a working-memory task. Our results provide evidence for fine-grained gradients related to certain neural dynamics. Moreover, we show that these timescales depend on and can be modulated by training in a cognitive task, and contribute to encoding of task-relevant information at single-cell and population levels.