Boundary of ecosystem services: Differentiating between ecosystem services and geosystem services is needed.

Geosystem services (GSs) and ecosystem services (ESs) are interconnected, both representing nature's contributions to people. Whether GSs are a subset of ESs depends on the definition of ESs. The answer would be "not necessarily" (i.e., some GSs are, while other GSs are not), if ESs are the benefits humans derive from ecological functions, processes, or characteristics. The boundary proposed by Chen et al. (2023) to differentiate ESs from other ecosystem-related benefits adopted this definition, and suggested that ESs are renewable and affected by biotic elements to occur. Gray et al. (2024) criticized this boundary for separating out bits of nature and ignoring the contributions of GSs and abiotic elements to ESs and human wellbeing. In fact, highlighting that ESs are affected by biotic elements to occur does not deny that ESs' occurrence is also affected by abiotic elements. However, ESs' dependence on abiotic elements cannot be a criterion to differentiate ESs from other benefits because abiotic elements are integral to geosystems, ecosystems, and many other natural and artificial systems, as well as to these systems' services. Conversely, while geosystems might persist without biotic elements, ecosystems cannot. Chen et al. (2023) only excluded those (not the whole) abiotic benefits, such as wind energy, that may occur independently of biotic elements, while allowing for integrating certain GSs into ESs. For example, geological structures can offer flood protection and water storage as GSs, which can also be classified as ESs when their qualities or quantities are affected by biotic elements. Differentiation between GSs and ESs should not be misinterpreted as splitting their interconnections or undervaluing or dividing nature. Instead, such differentiation and classification of nature's benefits serve to facilitate communication, management, education, research, and policy-making associated with nature's benefits, while also highlighting the richness and diversity of nature's benefits.

Exploring the complex trade-offs and synergies of global ecosystem services.

The trade-off and synergy relationship of ecosystem services is an important topic in the current assessment. The value of each service provided by the ecosystem is substantially affected by human activities, and conversely, its changes will also affect the relevant human decisions. Due to varying trade-offs among ecosystem services and synergies between them that can either increase or decrease, it is difficult to optimize multiple ecosystem services simultaneously, making it a huge challenge for ecosystem management. This study firstly develops a global Gross Ecosystem Product (GEP) accounting framework. It uses remote sensing data with a spatial resolution of 1 km to estimate the ecosystem services of forests, wetlands, grasslands, deserts, and farmlands in 179 major countries in 2018. The results show that the range of global GEP values is USD 112-197 trillion, with an average value of USD 155 trillion (the constant price), and the ratio of GEP to gross domestic product (GDP) is 1.85. The trade-offs and the synergies among different ecosystem services in each continent and income group have been further explored. We found a correspondence between the income levels and the synergy among ecosystem services within each nation. Among specific ecosystem services, there are strong synergies between oxygen release, climate regulation, and carbon sequestration services. A trade-off relationship has been observed between flood regulation and other services, such as water conservation and soil retention services in low-income countries. The results will help clarify the roles and the feedback mechanisms between different stakeholders and provide a scientific basis for optimizing ecosystem management and implementing ecological compensation schemes to enhance human well-being.

Pain and itch coding mechanisms of polymodal sensory neurons.

Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD+ neurons represent a major polymodal population and mediate both mechanical pain and nonhistaminergic itch. Here, we show that chemogenetic activation of MrgprD+ neurons elicited both pain- and itch-related behavior in a dose-dependent manner, revealing an unanticipated compatibility between pain and itch in polymodal neurons. While VGlut2-dependent glutamate release is required for both pain and itch transmission from MrgprD+ neurons, the neuropeptide neuromedin B (NMB) is selectively required for itch signaling. Electrophysiological recordings further demonstrated that glutamate synergizes with NMB to excite NMB-sensitive postsynaptic neurons. Ablation of these spinal neurons selectively abolished itch signals from MrgprD+ neurons, without affecting pain signals, suggesting a dedicated itch-processing central circuit. These findings reveal distinct neurotransmitters and neural circuit requirements for pain and itch signaling from MrgprD+ polymodal sensory neurons, providing new insights on coding and processing of pain and itch.

On-Surface Synthesis of Novel Kagome Lattices Coordinated via Four-Fold N-Ag Bonding.

The Kagome lattice structures based on metal-organic coordination have garnered widespread interest because of their topologically Dirac/flat bands and other exotic electronic structures. However, the experimental fabrication of large-area two-dimensional (2D) Kagome lattice structures of metal-organic frameworks (MOFs) via on-surface synthesis remains limited. Herein, we successfully construct two kinds of large-scale 2D Kagome-type lattices stabilized by 4-fold N-Ag coordination on the Ag(111) surface. With the aid of scanning tunneling microscopy (STM) and synchrotron radiation photoemission spectroscopy (SRPES), we clearly elucidate the reaction pathway and mechanism of fabrication of the two Kagome lattices. This work provides a novel platform for investigating related intriguing physical properties.

Boundary of ecosystem services: Guiding future development and application of the ecosystem service concepts.

Ecosystem Services (ESs) are either material or non-material benefits humans receive from ecosystems. Definitions, classifications, and typologies of ESs can vary to address different research and policy purposes. However, a boundary that distinguishes ESs from other ecosystem-related benefits (e.g., industrial products that consume raw materials, fossil fuels that used to be a part of ecosystems) is needed to avoid the risk of using ESs as an all-encompassing metaphor that captures any benefit. The boundary also maintains a common ground for communication and comparison of ESs across studies. To guide future development and application of the ES concepts, we suggest five criteria. ESs are (1) primary contributions of ecosystems, (2) flows assessed during a period or per time unit (not stock existing at a time point), (3) renewable (having the potential to be reproduced with a conceivable timeframe relevant to human use), (4) affected by biotic parts of ecosystems to occur. ESs include both biotic and some abiotic flows (e.g., water provisioning) but exclude abiotic flows (e.g., wind and solar energy) whose occurrence is unaffected by ecosystem functions, processes, or characteristics; and (5) inclusive to the benefits humans actually and potentially receive from ecosystems. These criteria link ESs with conservation of life-supporting and culturally important ecosystems, recognize use, option, and non-use values of ESs, and highlight ESs' sustainability.

Synthesis of a Porous [14]Annulene Graphene Nanoribbon and a Porous [30]Annulene Graphene Nanosheet on Metal Surfaces.

The electrical and mechanical properties of graphene-based materials can be tuned by the introduction of nanopores, which are sensitively related to the size, morphology, density, and location of nanopores. The synthesis of low-dimensional graphene nanostructures containing well-defined nonplanar nanopores has been challenging due to the intrinsic steric hindrance. Herein, we report the selective synthesis of one-dimensional (1D) graphene nanoribbons (GNRs) containing periodic nonplanar [14]annulene pores on Ag(111) and two-dimensional (2D) porous graphene nanosheet containing periodic nonplanar [30]annulene pores on Au(111), starting from a same precursor. The formation of distinct products on the two substrates originates from the different thermodynamics and kinetics of coupling reactions. The reaction mechanisms were confirmed by a series of control experiments, and the appropriate thermodynamic and kinetic parameters for optimizing the reaction pathways were proposed. In addition, the combined scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations revealed the electronic structures of porous graphene structures, demonstrating the impact of nonplanar pores on the π-conjugation of molecules.

Fluorescence recovery based on synergetic effect for ALP detection.

Alkaline phosphatase (ALP) is an important biomarker associated with diabetes, liver dysfunction, bone diseases, and breast cancer. Here we developed a method based on synergetic fluorescence recovery for the sensitive detection of ALP. Cadmium-zinc-selenium (CdZnSe) quantum dots (QDs) were prepared by one-pot water bath method without any complicated and rigorous conditions. CdZnSe QDs displayed high luminous efficiency, good stability, and good biocompatibility. KMnO4 and ascorbic acid phosphate (AAP) can dynamically quench the fluorescence of CdZnSe QDs. Ascorbic acid, produced by ALP-catalyzed hydrolysis of AAP, reacted with KMnO4, causing the synergetic fluorescence recovery of CdZnSe QDs. The synergetic recovery efficiency correlates well with the logarithmic ALP concentration in the range of 2.5-250 U/L with a detection limit of 0.21 U/L. In addition, good recoveries were obtained in the detection of ALP in human serum. This method provided a new research idea to improve the detection sensitivity and selectivity of ALP detection.

LLPSDB v2.0: an updated database of proteins undergoing liquid-liquid phase separation in vitro.

SUMMARY: Emerging evidences have suggested that liquid-liquid phase separation (LLPS) of proteins plays a vital role both in a wide range of biological processes and in related diseases. Whether a protein undergoes phase separation not only is determined by the chemical and physical properties of biomolecule themselves, but also is regulated by environmental conditions such as temperature, ionic strength, pH, as well as volume excluded by other macromolecules. A web accessible database LLPSDB was developed recently by our group, in which all the proteins involved in LLPS in vitro as well as corresponding experimental conditions were curated comprehensively from published literatures. With the rapid increase of investigations in biomolecular LLPS and growing popularity of LLPSDB, we updated the database, and developed a new version LLPSDB v2.0. In comparison of the previously released version, more than double contents of data are curated, and a new class 'Ambiguous system' is added. In addition, the web interface is improved, such as that users can search the database by selecting option 'phase separation status' alone or combined with other options. We anticipate that this updated database will serve as a more comprehensive and helpful resource for users. AVAILABILITY AND IMPLEMENTATION: LLPSDB v2.0 is freely available at: http://bio-comp.org.cn/llpsdbv2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem.

Sneezing is a vital respiratory reflex frequently associated with allergic rhinitis and viral respiratory infections. However, its neural circuit remains largely unknown. A sneeze-evoking region was discovered in both cat and human brainstems, corresponding anatomically to the central recipient zone of nasal sensory neurons. Therefore, we hypothesized that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing in this region. By screening major presynaptic neurotransmitters/neuropeptides released by nasal sensory neurons, we found that neuromedin B (NMB) peptide is essential for signaling sneezing. Ablation of NMB-sensitive postsynaptic neurons in the sneeze-evoking region or deficiency in NMB receptor abolished the sneezing reflex. Remarkably, NMB-sensitive neurons further project to the caudal ventral respiratory group (cVRG). Chemical activation of NMB-sensitive neurons elicits action potentials in cVRG neurons and leads to sneezing behavior. Our study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.

Methotrexate, a small molecular scaffold targeting Kv1.3 channel extracellular pore region.

Methotrexate (MTX) has been widely used for the treatment of many types of autoimmune diseases, such as rheumatoid arthritis, psoriasis and dermatomyositis. However, its pharmacological mechanism is still unclear completely. In this study, we found that MTX is a potent and selective inhibitor of the Kv1.3 channel, a class of potassium channels highly associated with autoimmune diseases. Electrophysiological experiments showed that MTX inhibited human Kv1.3 channel with an IC50 of 41.5 ± 24.9 nM, and 1 µM MTX inhibited 32.6 ± 1.3% and 25.6 ± 2.2% of human Kv1.1 and Kv1.2 channel currents, respectively. These data implied the unique selectivity of MTX towards the Kv1.3 channel. Excitingly, using channel activation and chimeric experiments, we found that MTX bound to the outer pore region of Kv1.3 channel. Mutagenesis experiments in the Kv.3 channel extracellular pore region further showed that the Dsp371, Thr373 and His399 residues of outer pore region of Kv1.3 channel played important roles in MTX inhibiting activities. In conclusion, MTX inhibited Kv1.3 channel by targeting extracellular pore region, which is different form all the report small molecules, such as PAP-1 and 4-AP, but similar with many natural animal toxin peptides, such as ChTX, ShK and BmKTX. To the best of our knowledge, MTX is the first small molecular scaffold targeting the Kv1.3 channel extracellular pore region, suggesting its potential applications for designing novel Kv1.3 lead drugs and treating Kv1.3 channel-associated autoimmune diseases.

Protein Databases Related to Liquid-Liquid Phase Separation.

Liquid-liquid phase separation (LLPS) of biomolecules, which underlies the formation of membraneless organelles (MLOs) or biomolecular condensates, has been investigated intensively in recent years. It contributes to the regulation of various physiological processes and related disease development. A rapidly increasing number of studies have recently focused on the biological functions, driving, and regulating mechanisms of LLPS in cells. Based on the mounting data generated in the investigations, six databases (LLPSDB, PhaSePro, PhaSepDB, DrLLPS, RNAgranuleDB, HUMAN CELL MAP) have been developed, which are designed directly based on LLPS studies or the component identification of MLOs. These resources are invaluable for a deeper understanding of the cellular function of biomolecular phase separation, as well as the development of phase-separating protein prediction and design. In this review, we compare the data contents, annotations, and organization of these databases, highlight their unique features, overlaps, and fundamental differences, and discuss their suitable applications.

Extensive solar light harvesting by integrating UPCL C-dots with Sn2Ta2O7/SnO2: Highly efficient photocatalytic degradation toward amoxicillin.

The carbon dots (C-dots) mediated Sn2Ta2O7/SnO2 heterostructures with spongy structure were successfully assembled by simple hydrothermal route. The photocatalytic removal efficiency of amoxicillin (AMX, 20 mg L-1) over C-dots/Sn2Ta2O7/SnO2 was estimated to reach up 88.3% within 120 min simulated solar light irradiating. Meanwhile, the HPLC-MS/MS analysis and density functional theory (DFT) computation were examined to clarify the photo-degradation pathway of AMX. The mechanism investigation proposed that with the modification of C-dots, the photocatalysts improves the utilization of solar energy by harvesting the long wavelength solar light due to their unique up-converted photoluminescence (UCPL). In addition, the porous spongy structure and plenty of tiny C-dots promote the ability of adsorption by enlarged specific surface area. Furthermore, the C-dots mediated Z-type heterojunction of Sn2Ta2O7/SnO2 facilitates the efficient separation and transfer of photo-induced carriers. Our work affords a promising approach for the design of the high-efficient photocatalysts to remedy poisonous antibiotics in aqueous environment.

The valuation of China's environmental degradation from 2004 to 2017.

This paper aims to evaluate the cost of environmental degradation by adopting the conventional environmental economic methodology in China from 2004 to 2017 and summarize the change in both the causes and costs of China's environmental degradation. Results from this study revealed the following: i. The environmental degradation cost in China increased from 511 billion yuan to 1,892 billion yuan from 2004 to 2017, and its share in the GDP decreased from 3.05% to 2.23%; ii. The environmental degradation cost growth rate was lower than the GDP growth rate. The environmental degradation cost growth rate decreased sharply, by dropping from 10% in 2014 to 2% in 2017. The environmental benefits of industrial transformation have emerged; iii. The provinces of Shandong, Hebei, Jiangsu, Henan, and Guangdong had the highest environmental degradation costs. The annual average growth rate of the environmental degradation costs in Jiangsu, Guangdong, and Zhejiang were lower than their growth rate of the GDP respectively; iv. Consideration of environmental degradation cost in decision-making could contribute to the high-quality development of China.

TRPV1 activity and substance P release are required for corneal cold nociception.

As a protective mechanism, the cornea is sensitive to noxious stimuli. Here, we show that in mice, a high proportion of corneal TRPM8+ cold-sensing fibers express the heat-sensitive TRPV1 channel. Despite its insensitivity to cold, TRPV1 enhances membrane potential changes and electrical firing of TRPM8+ neurons in response to cold stimulation. This elevated neuronal excitability leads to augmented ocular cold nociception in mice. In a model of dry eye disease, the expression of TRPV1 in TRPM8+ cold-sensing fibers is increased, and results in severe cold allodynia. Overexpression of TRPV1 in TRPM8+ sensory neurons leads to cold allodynia in both corneal and non-corneal tissues without affecting their thermal sensitivity. TRPV1-dependent neuronal sensitization facilitates the release of the neuropeptide substance P from TRPM8+ cold-sensing neurons to signal nociception in response to cold. Our study identifies a mechanism underlying corneal cold nociception and suggests a potential target for the treatment of ocular pain.

Conopeptides promote itch through human itch receptor hMgprX1.

Members of Mas related G-protein coupled receptors (Mrgpr) are known to mediate itch. To date, several compounds have been shown to activate these receptors, including chloroquine, a common antimalarial drug, and peptides of the RF-amide family. However, specific ligands for these receptors are still lacking and there is a need for novel compounds that can be used to modulate the receptors in order to understand the cellular and molecular mechanism in which they mediate itch. Some cone snail venoms were previously shown to induce itch in mice. Here, we show that the venom of Conus textile induces itch through activation of itch-sensing sensory neurons, marked by their sensitivity to chloroquine. Two RF-amide peptides, CNF-Tx1 and CNF-Tx2, were identified in a C. textile venom gland transcriptome. These belong to the conorfamide family of peptides which includes previously described peptides from the venoms of Conus victoriae (CNF-Vc1) and Conus spurius (CNF-Sr1 and CNF-Sr2). We show that CNF-Vc1 and CNF-Sr1 activate MrgprC11 whereas CNF-Vc1 and CNF-Tx2 activate the human MrgprX1 (hMrgprX1). The peptides CNF-Tx1 and CNF-Sr2 do not activate MrgprC11 or hMrgprX1. Intradermal injection of CNF-Vc1 and CNF-Tx2 into the cheek of a transgenic mouse expressing hMrgprX1 instead of endogenous mouse Mrgprs resulted in itch-related scratching thus demonstrating the in vivo activity of these peptides. Using truncated analogues of CNF-Vc1, we identified amino acids at positions 7-14 as important for activity against hMrgprX1. The conopeptides reported here are tools that can be used to advance our understanding of the cellular and molecular mechanism of itch mediated by Mrgprs.

Anatomical and functional dichotomy of ocular itch and pain.

Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most ocular pain arises from the cornea. However, the underlying mechanisms remain unknown. Using genetic axonal tracing approaches, we discover distinct sensory innervation patterns between the conjunctiva and cornea. Further genetic and functional analyses in rodent models show that a subset of conjunctival-selective sensory fibers marked by MrgprA3 expression, rather than corneal sensory fibers, mediates ocular itch. Importantly, the actions of both histamine and nonhistamine pruritogens converge onto this unique subset of conjunctiva sensory fibers and enable them to play a key role in mediating itch associated with allergic conjunctivitis. This is distinct from skin itch, in which discrete populations of sensory neurons cooperate to carry itch. Finally, we provide proof of concept that selective silencing of conjunctiva itch-sensing fibers by pruritogen-mediated entry of sodium channel blocker QX-314 is a feasible therapeutic strategy to treat ocular itch in mice. Itch-sensing fibers also innervate the human conjunctiva and allow pharmacological silencing using QX-314. Our results cast new light on the neural mechanisms of ocular itch and open a new avenue for developing therapeutic strategies.

St20, a new venomous animal derived natural peptide with immunosuppressive and anti-inflammatory activities.

Peptide toxins from venomous animals are natural resources with diverse biological functions and therapeutic potential towards human diseases. For venomous scorpions, many valuable peptide toxins have been discovered from Buthidae scorpions, but few works were done about non-buthidae scorpions. Here, we cloned and characterized the first disulfide-bridged toxin peptide St20 from the non-buthidae scorpion Scorpiops tibetanus. St20 has a putative 23-residue signal peptide, followed by a presumed 34-residue mature peptide including 8 cysteines. Sequence alignments and structural analysis suggested that St20 is a new member of α-KTx23 scorpion toxin subfamily with a conserved CSα/ß structural fold. Functional studies showed that St20 inhibited human T lymphocyte surface marker CD69 expression and cytokine IL-2 secretion. Beside this, St20 inhibited two important pro-inflammatory factors TNF-α and IFN-γ secretion in the activated human T lymphocyte. Animal experiments showed that the delayed-type hypersensitivity response in rat autoimmune disease model was ameliorated in the present of peptide toxin St20. Together, our results showed that St20 is the first disulfide-bridged toxin peptide from the non-buthidae scorpion Scorpiops tibetanus with immunosuppressive and anti-inflammatory activities, suggesting that toxins from non-buthidae scorpions might be a new source of peptide drug discovery towards human diseases.

Molecular basis for the toxin insensitivity of scorpion voltage-gated potassium channel MmKv1.

Scorpions are insensitive to their own venoms, which contain various neurotoxins specific for mammalian or insect ion channels, whose molecular mechanism remains unsolved. Using MmKv1, a potassium channel identified from the genome of the scorpion Mesobuthus martensii, channel kinetic experiments showed that MmKv1 was a classical voltage-gated potassium channel with a voltage-dependent fast activation and slow inactivation. Compared with the human Kv1.3 channel (hKv1.3), the MmKv1 channel exhibited a remarkable insensitivity to both scorpion venom and toxin. The chimaeric channels of MmKv1 and hKv1.3 revealed that both turret and filter regions of the MmKv1 channel were critical for the toxin insensitivity of MmKv1. Furthermore, mutagenesis of the chimaeric channel indicated that two basic residues (Arg(399) and Lys(403)) in the MmKv1 turret region and Arg(425) in the MmKv1 filter region significantly affected its toxin insensitivity. Moreover, when these three basic residues of MmKv1 were simultaneously substituted with the corresponding residues from hKv1.3, the MmKv1-R399T/K403S/R425H mutant channels exhibited similar sensitivity to both scorpion venom and toxin to hKv1.3, which revealed the determining role of these three basic residues in the toxin insensitivity of the MmKv1 channel. More strikingly, a similar triad sequence structure is present in all Shaker-like channels from venomous invertebrates, which suggested a possible convergent functional evolution of these channels to enable them to resist their own venoms. Together, these findings first illustrate the mechanism by which scorpions are insensitive to their own venoms at the ion channel receptor level and enrich our knowledge of the insensitivity of scorpions and other venomous animals to their own venoms.

Human beta-defensin 1, a new animal toxin-like blocker of potassium channel.

The discovery of human ß-defensin 2 (hBD2), as a Kv1.3 channel inhibitor with the unique molecular mechanism and novel immune modulatory function, suggests that human ß-defensins are a novel class of channel ligands. Here, the function and mechanism of the human ß-defensin 1 (hBD1) binding to potassium channels was investigated. Based on the structural similarity between hBD1 and Kv1.3 channel-sensitive hBD2, hBD1 was found to selectively inhibit human and mouse Kv1.3 channels with IC50 values of 11.8 ± 3.1 µM and 13.2 ± 4.0 µM, respectively. Different from hBD2 modifying Kv1.3 channel activation and increasing activation time constant, hBD1 did not affect the activation feature of both human and mouse Kv1.3 channels. In comparison with hBD2 simultaneously interacting with the extracellular S1-S2 linker and pore region of Kv1.3 channel, the chimeric channel and mutagenesis experiments showed that hBD1 only bound to the extracellular pore region of Kv1.3 channel instead of extracellular S1-S2 linker or S3-S4 linker. Together, these findings enhance knowledge of hBD1 as a new immune-related Kv1.3 channel blocker and highlight the major functional differences between hBD1 and hBD2 to explore in future research.