Maximizing carbon sequestration potential in Chinese forests through optimal management.

Forest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1-3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement.

Pyrococcus furiosus argonaute combined with loop-mediated isothermal amplification for rapid, ultrasensitive, and visual detection of fowl adenovirus serotype 4.

Since 2015, an outbreak of an infectious disease in broilers caused by fowl adenovirus serotype 4 (FAdV-4) has occurred in China, resulting in substantial economic losses. Rapid, accurate, and specific detection are significant in the prevention and control of FAdV-4. In this study, an FAdV-4 detection method combining loop-mediated isothermal amplification (LAMP) and Pyrococcus furiosus Argonaute (PfAgo) was established. Specific primers, guide DNAs (gDNAs), and molecular beacons were designed to target a conserved region of the FAdV-4 hexon gene. After optimizing the reaction conditions, the minimum detection of this assay could reach 5 copies. It only amplified FAdV-4, and there was no cross-reactivity with other pathogens. The assay took about only 50 min, and the results could be visualized with the naked eye under ultraviolet or blue light, getting rid of specialized instruments. This novel LAMP-PfAgo assay was validated by using 20 clinical samples and the results were identical to gold-standard real-time polymerase chain reaction method. In summary, the LAMP-PfAgo assay established in the paper provides a rapid, reliable, convenient, ultra-sensitive and highly specific tool for the on-site detection and clinical diagnosis of FAdV-4.

Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors.

The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Novel magnetic porous organic polymer containing amino and triazine bifunctional groups for efficient adsorption of nitroimidazoles.

In this paper, a novel magnetic hyper-crosslinked polymer with amino and triazine bifunctional groups (M-NH2-THCP) was developed. M-NH2-THCP has strong nitroimidazoles (NDZs) enrichment effect, and therefore it was used as an adsorbent to extract five NDZs from lake water, catfish and shrimp meat prior to HPLC. Polar interaction, π-π stacking interaction, hydrogen bond and Lewis acid-base interaction were attested to be the major adsorption mechanism. The method has a good linearity in the range of 0.1-100 ng mL-1 for lake water, 10-400 ng g-1 for catfish and shrimp muscle with R2 > 0.9964. The limits of detection of NDZs were 0.03-0.04 ng mL-1 for lake water, 1.0-2.0 ng g-1 for catfish and 2.0-2.5 ng g-1 for shrimp, which is superior to most reported method. The method recoveries were 87.6-119 %, and relative standard deviations were less than 8.7 %. M-NH2-THCP holds great application potential in pollutants enrichment, separation and removal.

Ursonic acid attenuates spermatogenesis in oligozoospermia mice through inhibiting ferroptosis.

Ursonic acid (UNA) is a natural pentacyclic triterpene found in some medicinal plants and foods. The reproductive protective effect of UNA was evaluated in a mouse model of oligozoospermia induced by busulfan (BUS) at 30 mg/kg b.w.. The mice were initially divided into groups with UNA concentrations of 10, 30, 50, 100 mg/kg. Subsequently, based on sperm parameters, the optimal concentration of 50 mg/kg was identified. As a control, an additional group was supplemented with ursolic acid at a concentration of 50 mg/kg. The results indicated that BUS caused the loss of spermatogenic cells in testis, the decrease of sperm in epididymis, the disorder of testicular cytoskeleton, the decrease of serum sex hormones such as testosterone which induced an increase in feedback of androgen receptor and other testosterone-related proteins, the increase of malondialdehyde and reactive oxygen species levels and the increase of ferroptosis in testis while UNA successfully reversed these injuries. High-throughput sequencing revealed that UNA administration significantly upregulated the expression of genes associated with spermatogenesis, such as Tnp1, Tnp2, Prm1, among others. These proteins are crucial in the histone to protamine transition during sperm chromatin remodeling. Network pharmacology analysis reveals a close association between UNA and proteins related to the transformation of histones to protamine. Molecular docking studies reveal that UNA can interact with the ferroptosis-inhibiting gene SLC7A11, thereby modulating ferroptosis. Taken together, UNA alleviated BUS-induced oligozoospermia by regulating hormone secretion, mitigating oxidative stress and promoting recovery of spermatogenesis by inhibiting the ferroptosis.

Fabrication of chitin based hydrophilic hyper-crosslinked porous polymer for efficiently removing bisphenol A from water.

Water pollution caused by bisphenol A (BPA) has become the world problem. Designing and preparing cost-effective and biodegradable sorbents for the effectively adsorptive removal of bisphenol A from wastewater is of immense significance. Herein, a natural polysaccharide (chitin) was used as raw materials to be grafted with styrene (GS), then crosslinked with α,α'-dichloro-p-xylene (DCX) to form the hyper-crosslinked polymer (labeled as CGS@DCX). The CGS@DCX showed high adsorptive affinity for bisphenol A, with adsorption capacity of 441 mg g-1. Various studies gave an insight into the adsorption process, demonstrating that the highly efficient adsorption of BPA by the CGS@DCX is mainly based on the π-π stacking, hydrogen-bond interaction, polar interaction and pore adsorption. Moreover, the CGS@DCX had high chemical stability, good reusability (9 cycles) and fast adsorption kinetics (10 min) for adsorption of BPA. This work provides a promising strategy for the design and synthesis of novel yet eco-friendly sorbents to solve environmental problems.

Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400.

Sodium-calcium exchanger proteins influence calcium homeostasis in many cell types and participate in a wide range of physiological and pathological processes. Here, we elucidate the cryo-EM structure of the human Na+/Ca2+ exchanger NCX1.3 in the presence of a specific inhibitor, SEA0400. Conserved ion-coordinating residues are exposed on the cytoplasmic face of NCX1.3, indicating that the observed structure is stabilized in an inward-facing conformation. We show how regulatory calcium-binding domains (CBDs) assemble with the ion-translocation transmembrane domain (TMD). The exchanger-inhibitory peptide (XIP) is trapped within a groove between the TMD and CBD2 and predicted to clash with gating helices TMs1/6 at the outward-facing state, thus hindering conformational transition and promoting inactivation of the transporter. A bound SEA0400 molecule stiffens helix TM2ab and affects conformational rearrangements of TM2ab that are associated with the ion-exchange reaction, thus allosterically attenuating Ca2+-uptake activity of NCX1.3.

Hydrochar-Supported NiFe2O4Nanosheets with a Tailored Microstructure for Enhanced CO2Photoreduction to Syngas.

Constructing high-efficiency composite photocatalysts with enhanced charge transfer and a rapid surface catalytic reaction has recently received significant attention. Herein, a hydrochar-mediated NiFe2O4 nanosheet (C/NFO) composite was rationally constructed by a simple hydrothermal method. Intimate interface contacts and chemical interactions between hydrochar and NFO were formed. The prepared C/NFO samples exhibited remarkable visible-light-driven catalytic CO2 reduction properties under mild reaction conditions with Ru(bpy)32+ sensitization. As the optimized sample, 16%-C/NFO achieved a 4-fold enhancement of CO production (17.49 µmol/h) compared with that of pure NFO. The C/NFO samples demonstrated good activity and structural stability in the CO2 photoreduction system. The carbon source of CO derived from CO2 was verified through isotopic labeling experiments using 13CO2. In situ photoluminescence and electrochemical characterizations confirmed the role of electron transfer intermediates of C/NFO. The synergistic effect of the nanosheet-like structure of NFO, combined with the surface functional groups of hydrochar, facilitated an exceptionally high rate of charge transfer and exposed abundant active adsorption sites for CO2, thereby promoting the efficient separation of photogenerated charge carriers and enhancing photocatalytic activity for CO2 reduction. This study presents a promising strategy for the rational design of hydrochar coupled with transition metal compound catalysts for efficient CO2 photoreduction.

A chitin-based magnetic hyper-cross-linked polymer for highly efficient enrichment of neonicotinoids in lemon juice and tomatoes.

A chitin-based magnetic hyper-cross-linked polymer (labeled as Ch-MHCP) has been successfully synthesized and utilized for highly-effective solid-phase extraction of neonicotinoid insecticides (NEOs). The extraction capability of Ch-MHCP for four common NEOs is higher than that of four commercial sorbents including octadecyl-silane C18, oasis hydrophilic/lipophilic balanced sorbent, oasis mixed anion sorbent and poly-phenylacetic mixed anion sorbent. The large number of hydroxyl and amide groups as well as benzene rings in Ch-MHCP allow the H-bond and π-π* interaction to be the principal adsorption mechanism of Ch-MHCP for NEOs. Besides, polar interaction was also involved in the adsorption process. In combination of Ch-MHCP based extraction technique with high-performance liquid chromatography, a novel analytical method for sensitive detection of NEOs in lemon juice and tomatoes has been established. At optimal conditions, wide linear ranges were obtained to be 0.20-100 ng mL-1 for lemon juice and 0.80-1000 ng g-1 for tomatoes. The detection limits were 0.06-0.12 ng mL-1 for lemon juice and 0.24-0.60 ng g-1 for tomatoes. This work not only provides a powerful tool for simultaneously detecting four NEOs in lemon juice and tomatoes, but also offers a new insight into the preparation of bio-based magnetic sorbents for adsorption/removal of pollutants.

Rapid Raman spectroscopic identification of three homoisoflavanones in polygonatum odoratum based on twice chromatography derivatization.

The aim of this study was to establish a new method for the determination of homoisoflavanones (Ⅲ, Ⅳ, V) in polygonatum odoratum(POD) by combination of thin layer chromatography (TLC) and chemical derivative resonance Raman spectroscopy (RRS). The twice chromatography method of TLC was used to improve the specificity of the component to be tested; the method of the relative Rf was used to reduce the use of the reference substance of the component to be tested; the chemical derivatization method was used to improve the signal intensity of Raman spectrum for the component to be tested in POD, so as to obtain a trace amount fingerprint structure information of the measured component. The method exhibits robust specificity, high sensitivity, and reliable stability, there by offering a novel reference approach for the identification and evaluation of homoisoflavanones (Ⅲ, Ⅳ, V) in POD.

Synthesis of phosphate-functionalized magnetic porous organic polymer: A sorbent for sensitive determination of neonicotinoid insecticides in water and lemon juice.

There is an urgent need to prepare advanced functional materials for extraction and enrichment of trace organic pollutants from different samples. In this work, two novel phosphate-functionalized porous organic polymers (DBP-POP and DPP-POP) were synthesized for the first time. Compared with phosphate-free counterpart, both phosphate-functionalized POPs showed excellent adsorption performance for the neonicotinoids due to the hydrogen bonding, π-π interaction and hydrophobic interaction. For ease of separating the sorbent from solution, magnetic DBP-POP (M-DBP-POP) was further prepared as sorbent to extract neonicotinoids from environmental water and lemon juice samples prior to their determination by high performance liquid chromatography-ultraviolet detection. Under optimal conditions, the detection limits (S/N = 3) of the method were 0.01-0.08 ng mL-1 for water and 0.03-0.10 ng mL-1 for lemon juice. The recoveries were in the range of 80.0% to 113.0% with relative standard deviation less than 10.6%. This work demonstrated the feasibility of phosphate-functionalized POPs for adsorption applications.

Architecture and autoinhibitory mechanism of the plasma membrane Na+/H+ antiporter SOS1 in Arabidopsis.

Salt-overly-sensitive 1 (SOS1) is a unique electroneutral Na+/H+ antiporter at the plasma membrane of higher plants and plays a central role in resisting salt stress. SOS1 is kept in a resting state with basal activity and activated upon phosphorylation. Here, we report the structures of SOS1. SOS1 forms a homodimer, with each monomer composed of transmembrane and intracellular domains. We find that SOS1 is locked in an occluded state by shifting of the lateral-gate TM5b toward the dimerization domain, thus shielding the Na+/H+ binding site. We speculate that the dimerization of the intracellular domain is crucial to stabilize the transporter in this specific conformation. Moreover, two discrete fragments and a residue W1013 are important to prevent the transition of SOS1 to an alternative conformational state, as validated by functional complementation assays. Our study enriches understanding of the alternate access model of eukaryotic Na+/H+ exchangers.

The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVE: There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers. METHODS: The study consisted of single ascending doses part (part 1: 25-600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile. RESULTS: In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (Tmax) of 1.50 to 3.00 h. The geometric median half-life (t1/2) of SHR2285 varied from 8.74 to 12.1 h across 25-600 mg single dose. Total systemic exposure of metabolite SHR164471 was approximately 1.77- to 3.61-fold that of the parent drug. The plasma concentration of SHR2285 and SHR164471 reached steady state by the morning of Day 7, with low accumulation ratio (0.956-1.20 and 1.18-1.56, respectively). The increase in pharmacokinetic exposure of SHR2285 and SHR164471 was less than dose proportional. Food has minimal effect on the pharmacokinetics of SHR2285 and SHR164471. SHR2285 produced an exposure-dependent prolongation of activated partial thromboplastin time (APTT) and a decrease in FXI activity. The maximum FXI activity inhibition rate (geometric mean) at steady state was 73.27%, 85.58%, 87.77% and 86.27% for 100-400 mg, respectively. CONCLUSIONS: SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile. CLINICALTRIALS: gov Identifier NCT04472819; registered on July 15, 2020.

Molecular Design of Porous Organic Polymer-Derived Carbonaceous Electrocatalysts for Pinpointing Active Sites in Oxygen Reduction Reaction.

The widespread application of fuel cells is hampered by the sluggish kinetics of the oxygen reduction reaction (ORR), which traditionally necessitates the use of high-cost platinum group metal catalysts. The indispensability of these metal catalysts stems from their ability to overcome kinetic barriers, but their high cost and scarcity necessitate alternative strategies. In this context, porous organic polymers (POPs), which are built up from the molecular level, are emerging as promising precursors to produce carbonaceous catalysts owning to their cost-effectiveness, high electrical conductivity, abundant active sites and extensive surface area accessibility. To enhance the intrinsic ORR activity and optimize the performance of these electrocatalysts, recognizing, designing, and increasing the density of active sites are identified as three crucial steps. These steps, which form the core of our review, serve to elucidate the link between the material structure design and ORR performance evaluation, thereby providing valuable insights for ongoing research in the field. Leveraging the precision of polymer skeletons based on molecular units, POP-derived carbonaceous catalysts provide an excellent platform for in-depth exploration of the role and working mechanism for the specific active site during the ORR process. In this review, the recent advances pertaining to the synthesis techniques and electrochemical functions of various types of active sites, pinpointed from POPs, are systematically summarized, including heteroatoms, surficial substituents and edge/defects. Notably, the structure-property relationship, between these active sites and ORR performance, are discussed and emphasized, which creates guidelines to shed light on the design of high-performance ORR electrocatalysts.

Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3.

High-voltage-activated R-type CaV2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we determine the high-resolution cryo-electron microscopy (cryo-EM) structure of human CaV2.3 in complex with the α2δ1 and ß1 subunits. The VSDII is stabilized in the resting state. Electrophysiological experiments elucidate that the VSDII is not required for channel activation, whereas the other VSDs are essential for channel opening. The intracellular gate is blocked by the W-helix. A pre-W-helix adjacent to the W-helix can significantly regulate closed-state inactivation (CSI) by modulating the association and dissociation of the W-helix with the gate. Electrostatic interactions formed between the negatively charged domain on S6II, which is exclusively conserved in the CaV2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5II helix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of CaV2 channels.

How does China's stock market react to supply chain disruptions from COVID-19?

As a once-in-a-century global pandemic, COVID-19 severely hit the global economy and disrupted the worldwide supply chain. Based on 505 Chinese firms, we use the event study method to explore the effect of COVID-19 on the financial performance of firms. The findings show that COVID-19 has an immediate impact on Chinese firms. Hubei firms experience stronger effects than non-Hubei firms. Supply chain disruptions effects from COVID-19 are observed. Transportation industry is hit more severely than retail industry. Insurance companies experience a strong adverse effect. On the other hand, both medical and competitor firms experience significantly positive spillover effects.

The effect of thermodynamic changes in the cooling of saline soils on the corrosion system of carbon steels.

In this experiment, Q235 and X80 carbon steels, which are widely used in oil and gas pipelines and ancillary facilities, were selected to study the changes in the corrosion behaviour and mechanism of carbon steels in the process of natural saline soil cooling to a freezing state through electrochemical testing. The equivalent circuit model of carbon steel before and after the freezing phase transformation in the soil was determined. Based on the corrosion kinetic parameters and soil thermodynamic changes, the influencing factors of steel corrosion during the cooling process were systematically analysed. It was found that temperature mainly affected carbon steel corrosion by changing the properties of the solution. The main factors affecting the corrosion behaviour of the carbon steel were the thermal motion of molecules, ions, and electrons in solution, oxygen dissolution and diffusion, ion adsorption, diffusion mass transfer, and unfrozen water content change during the cooling process.

SHR2285, the first selectively oral FXIa inhibitor in China: Safety, tolerability, pharmacokinetics and pharmacodynamics combined with aspirin, clopidogrel or ticagrelor.

Purpose: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR2285, the first oral coagulation factor XIa (FXIa) inhibitor developed in China in combination with aspirin, clopidogrel or ticagrelor in healthy subjects. Methods: This study was a single-center, randomized, double-blind, placebo-controlled (only SHR2285) design (NCT04945616). A total of 52 healthy subjects, 29 male and 23 female, were completed in this study. The subjects were divided into three groups: A, B and C, 16 subjects in group A [aspirin + clopidogrel + placebo or SHR2285 200 mg bid (1:3, 4 received placebo and 12 received SHR2285)] 16 subjects in group B [aspirin + clopidogrel + placebo or SHR2285 300 mg bid (1:3, 3 received placebo and 13 received SHR2285)] and 20 subjects in group C (aspirin + ticagrelor + placebo or SHR2285 300 mg bid (2:3, 8 received placebo and 12 received SHR2285)), respectively. All groups were administered orally for six consecutive days. Safety, tolerability, pharmacokinetics and pharmacodynamics parameters were assessed. Results: 1) SHR2285 was well tolerated, and all adverse events were mild. There was no evidence of an increased risk of bleeding. 2) After 6 days of twice-daily administration, SHR2285 could reach a steady state. The mean half-life of SHR2285 in group A, group B and group C was 13.9 h, 14.5 h and 13.8 h, respectively. 3) SHR2285 markedly inhibited FXI activity and prolonged activated partial thromboplastin time (APTT). In group A, group B and group C, the mean maximum inhibition rate of FXI activity was 84.8%, 89.3% and 92.2% and the mean maximum prolongation of APTT was 2.08-fold, 2.36-fold and 2.26-fold, respectively. Conclusion: These data suggest that SHR2285, a potential oral FXIa inhibitor, is expected to become a novel, safe and effective anticoagulant when combined with aspirin, clopidogrel or ticagrelor.

Structural basis of ligand binding modes of human EAAT2.

In the central nervous system (CNS), excitatory amino acid transporters (EAATs) mediate the uptake of excitatory neurotransmitter glutamate and maintain its low concentrations in the synaptic cleft for avoiding neuronal cytotoxicity. Dysfunction of EAATs can lead to many psychiatric diseases. Here we report cryo-EM structures of human EAAT2 in an inward-facing conformation, in the presence of substrate glutamate or selective inhibitor WAY-213613. The glutamate is coordinated by extensive hydrogen bonds and further stabilized by HP2. The inhibitor WAY-213613 occupies a similar binding pocket to that of the substrate glutamate. Upon association with the WAY-213613, the HP2 undergoes a substantial conformational change, and in turn stabilizes the inhibitor binding by forming hydrophobic interactions. Electrophysiological experiments elucidate that the unique S441 plays pivotal roles in the binding of hEAAT2 with glutamate or WAY-213613, and the I464-L467-V468 cluster acts as a key structural determinant for the selective inhibition of this transporter by WAY-213613.