CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.

INTRODUCTION: Owing to the limited treatment options for hepatocellular carcinoma (HCC), interventions targeting pre-HCC stages have attracted increasing attention. In the pre-HCC stage, hepatic tumor-initiating cells (hTICs) proliferate abnormally and contribute to hepatocarcinogenesis. Numerous studies have investigated targeted senescence induction as an HCC intervention. However, it remains to be clarified whether senescence induction of hTICs could serve as a pre-HCC intervention. OBJECTIVES: This study was designed to investigate whether senescence induction of hTICs in the precancerous stage inhibit HCC initiation. METHODS AND RESULTS: HCC models developed from chronic liver injury (CLI) were established by using Fah-/- mice and N-Ras + AKT mice. PD-0332991, a selective CDK4/6 inhibitor that blocks the G1/S transition in proliferating cells, was used to induce senescence during the pre-HCC stage. Upon administration of PD-0332991, we observed a significant reduction in HCC incidence following selective senescence induction in hTICs, and an alleviation liver injury in the CLI-HCC models. PD-0332991 also induced senescence in vitro in cultured hTICs isolated from CLI-HCC models. Moreover, RNA sequencing (RNA-seq) analysis delineated that the "Cyclin D-CDK4/6-INK4-Rb" pathway was activated in both mouse and human liver samples during the pre-HCC stage, while PD-0332991 exhibited substantial inhibition of this pathway, thereby inducing cellular senescence in hTICs. Regarding the immune microenvironment, we demonstrated that senescent hTICs secrete key senescence-associated secretory phenotypic (SASP) factors, CXCL10 and CCL2, to activate and recruit macrophages, and contribute to immune surveillance. CONCLUSION: We found that hTICs can be targeted and induced into a senescent state during the pre-HCC stage. The SASP factors released by senescent hTICs further activate the immune response, facilitating the clearance of hTICs, and consequently suppressing HCC occurrence. We highlight the importance of pre-HCC interventions and propose that senescence-inducing drugs hold promise for preventing HCC initiation under CLI.

Simultaneous Modification of Al3+/F- Cosubstitution to Construct a Solid Framework for Na3V2(PO4)3 with High Thermal Stability and Near-Zero Strain Performance.

Challenges related to poor electronic conductivity and cycling stability have impeded the development and utilization of Na3V2(PO4)3 (NVP). Therefore, this study focuses on enhancing the performance of NVP by employing a sol-gel method to design various gradients of F/Al-doped and carbon nanotube (CNT)-enwrapped NVP materials. The introduction of F doping replacing PO4 tetrahedra reduces the occupied space, while F monomers can establish stronger bonds with VO6 octahedral pillars closer to O atoms. Additionally, Al doping introduces a new AlO6 octahedral structure at the V site, strengthening the 3D framework. The synergistic substitution of F and Al contributes to improving the stability of the framework, which enhances the Na+ migration channels and overall electrochemical performance. Furthermore, the coating of CNTs plays a crucial role in creating a favorable interface transition layer that facilitates efficient electron transport and enhances electronic conductivity. Comprehensively, the modified FAl-2 exhibits a high capacity of 115.8 mA h g-1 at 0.1C. It reveals 89.3 mA h g-1 at 60C and maintains 83.8 mA h g-1 after 2000 cycles, indicating a capacity retention rate of 93.84%. Electrochemical ex situ X-ray diffraction (XRD) demonstrates that FAl-2 behaves at relatively low values (0.328%-1.075%) of volume shrinkage during the whole charge/discharge process, indicating its near-zero strain property. The postcycled XRD and X-ray photoelectron spectroscopy further verify the significantly enhanced crystal structural stability of FAl-2. Moreover, FAl-2 possesses a higher thermal runaway temperature, indicating a superior thermal stability. The self-releasing heat trend observed in FAl-2 can offer valuable insights into the design of battery management systems.

The Generation and Characterization of Monoclonal Antibodies against the MPXV A29L Protein.

Mpox (formerly known as monkeypox) is a zoonotic disease caused by monkeypox virus (MPXV), a DNA virus belonging to the Orthopoxvirus genus, in the Poxviridae family. The disease constitutes a moderate risk to public health at the global level. The MPXV A29L protein plays a crucial role in coordinating virion assembly and facilitating important virus-host interactions. This study focused on the expression, purification, and recombinant protein synthesis of the A29L protein of MPXV using prokaryotic systems. Using hybridoma technology, we successfully generated the monoclonal antibodies (mAbs) 1E12 and 4B2, which specifically recognize the A29L protein. These mAbs were found to be suitable for use in indirect immunofluorescence assays (IFA), Western blotting, and immunoprecipitation (IP). Our investigation also revealed that mAbs 1E12 and 4B2 could detect the A27L protein, a homologous protein found in the vaccinia virus Western Reserve (VACV WR) strain, using IFA, Western blotting, and immunoprecipitation (IP). Using mAbs 1E12 and 4B2 as primary immunological probes, A27L protein expression was detected as early as 6 h postinfection with VACV WR, with increasing protein levels being observed throughout the infection. This study enhances our understanding of the protein structure and function of MPXV and contributes to the development of specific MPXV detection methods.

Efficacy of ketamine versus esketamine in the treatment of perioperative depression: A review.

Depression is a significant factor contributing to postoperative occurrences, and patients diagnosed with depression have a higher risk for postoperative complications. Studies on cardiovascular surgery extensively addresses this concern. Several studies report that people who undergo coronary artery bypass graft surgery have a 20% chance of developing postoperative depression. A retrospective analysis of medical records spanning 21 years, involving 817 patients, revealed that approximately 40% of individuals undergoing coronary artery bypass grafting (CABG) were at risk of perioperative depression. Patients endure prolonged suffering from illness because each attempt with standard antidepressants requires several weeks to be effective. In addition, multi-drug combination adjuvants or combination medication therapy may alleviate symptoms for some individuals, but they also increase the risk of side effects. Conventional antidepressants primarily modulate the monoamine system, whereas different therapies target the serotonin, norepinephrine, and dopamine systems. Esketamine is a fast-acting antidepressant with high efficacy. Esketamine is the S-enantiomer of ketamine, a derivative of phencyclidine developed in 1956. Esketamine exerts its effect by targeting the glutaminergic system the glutaminergic system. In this paper, we discuss the current depression treatment strategies with a focus on the pharmacology and mechanism of action of esketamine. In addition, studies reporting use of esketamine to treat perioperative depressive symptoms are reviwed, and the potential future applications of the drug are presented.

Grazing exclusion is more effective for vegetation restoration and nutrient transfer in the heavily degraded desert steppe.

BACKGROUND: Grazing exclusion is an efficient practice to restore degraded grassland ecosystems by eliminating external disturbances and improving ecosystems' self-healing capacities, which affects the ecological processes of soil-plant systems. Grassland degradation levels play a critical role in regulating these ecological processes. However, the effects of vegetation and soil states at different degradation stages on grassland ecosystem restoration are not fully understood. To better understand this, desert steppe at three levels of degradation (light, moderate, and heavy degradation) was fenced for 6 years in Inner Mongolia, China. Community characteristics were investigated, and nutrient concentrations of the soil (0-10 cm depth) and dominant plants were measured. RESULTS: We found that grazing exclusion increased shoots' carbon (C) concentrations, C/N, and C/P, but significantly decreased shoots' nitrogen (N) and phosphorus (P) concentrations for Stipa breviflora and Cleistogenes songorica. Interestingly, there were no significant differences in nutrient concentrations of these two species among the three degraded desert steppes after grazing exclusion. After grazing exclusion, annual accumulation rates of aboveground C, N, and P pools in the heavily degraded area were the highest, but the aboveground nutrient pools were the lowest among the three degraded grasslands. Similarly, the annual recovery rates of community height, cover, and aboveground biomass in the heavily degraded desert steppe were the highest among the three degraded steppes after grazing exclusion. These results indicate that grazing exclusion is more effective for vegetation restoration in the heavily degraded desert steppe. The soil total carbon, total nitrogen, total phosphorus, available nitrogen, and available phosphorus concentrations in the moderately and heavily degraded desert steppes were significantly decreased after six years of grazing exclusion, whereas these were no changes in the lightly degraded desert steppe. Structural equation model analysis showed that the grassland degradation level mainly altered the community aboveground biomass and aboveground nutrient pool, driving the decrease in soil nutrient concentrations and accelerating nutrient transfer from soil to plant community, especially in the heavily degraded grassland. CONCLUSIONS: Our study emphasizes the importance of grassland degradation level in ecosystem restoration and provides theoretical guidance for scientific formulation of containment policies.

Sc3+ substituted Na3V2(PO4)3 on N-doped porous carbon skeleton boosting high structural stability and superior electrochemical performance for full sodium ion batteries.

The poor structural stability and conductivity of Na3V2(PO4)3 (NVP) have been serious limitations to its development. In this paper, Sc3+ is selected to replace partial site of V3+ which can enhance its ability to bond with oxygen, forming the ScO6 octahedral unit, resulting in improved structural stability and better kinetic properties for the NVP system. Moreover, due to the larger ionic radius of Sc3+ compared to V3+, moderate Sc3+ substitution can support the crystal framework as pillar ions and expand the migration channels for de-intercalation of Na+, thus efficiently promoting ionic conductivity. The introduction of polyacrylonitrile (PAN) to provide an N-doped porous carbon substrate is another key aspect. The low-cost carbon resource of PAN can induce a beneficial nitrogen-doped carbon skeleton with defects, enhancing electronic conductivity at the interface to reduce the polarization phenomenon. The established pore structure can serve as a buffer for unit cell deformation caused by Na+ migration. Furthermore, the enlarged specific surface area provides more active sites for electrolyte infiltration, improving the material utilization rate. The after cycling X-ray Diffraction/scanning electron microscope (XRD/SEM) further confirms the stabilized porous carbon skeleton and improved crystal stability of Sc-3 material. Ex-situ XRD analysis shows that the crystal volume change in the Sc-3 cathode is relatively slight but reversible during the charge/discharge process, indicating that Sc3+ doping plays a crucial role in stabilizing the unit cell structure. The hybrid Sc/VO6 and PO4 units jointly build a strong bone structure to resist stress and weaken deformation. Accordingly, the optimized Sc-3 sample reveals an initial capacity of 115.9 mAh/g at 0.1C, with a capacity retention of 78.6 % after 2000 cycles at 30C. The Sc-3//CHC full battery can release a capacity of 191.3 mAh/g at 0.05C, accompanied by successful illumination, showcasing its promising practical applications.

Facile Al2O3 coating suppress dissolution of Mn2+ in Mn-substituted Na3V2(PO4)3 with outstanding electrochemical performance for full sodium ion batteries.

Na3V2(PO4)3 (NVP) encounters significant obstacles, including limited intrinsic electronic and ionic conductivities, which hinder its potential for commercial feasibility. Currently, the substitution of V3+ with Mn2+ is proposed to introduce favorable carriers, enhancing the electronic conductivity of the NVP system while providing structural support and stabilizing the NASICON framework. This substitution also widens the Na+ migration pathways, accelerating ion transport. Furthermore, to bolster stability, Al2O3 coating is applied to suppress the dissolution of transition metal Mn in the electrolyte. Notably, the Al2O3 coating serves a triple role in reducing HClO4 concentration in the electrolyte, inhibiting Mn dissolution, and functioning as the ion-conducting phase. Likewise, carbon nanotubes (CNTs) effectively hinder the agglomeration of active particles during high-temperature sintering, thereby optimizing the conductivity of NVP system. In addition, the excellent structural stability is investigated by in situ XRD measurement, effectively improving the volume collapse during Na+ de-embedding. Moreover, the Na3V5.92/3Mn0.04(PO4)3/C@CNTs@1wt.%Al2O3 (NVMP@CNTs@1wt.%Al2O3) possesses unique porous structure, promoting rapid Na+ transport and increasing the interface area between the electrolyte and the cathode material. Comprehensively, the NVMP@CNTs@1wt.%Al2O3 sample demonstrates a remarkable reversible specific capacity of 122.6 mAh/g at 0.1 C. Moreover, it maintains a capacity of 115.9 mAh/g at 1 C with a capacity retention of 90.2 mAh/g after 1000 cycles. Even at 30 C, it achieves a capacity of 87.9 mAh/g, with a capacity retention rate of 84.87 % after 6000 cycles. Moreover, the NVMP@CNTs@1wt.%Al2O3//CHC full cell can deliver a high reversible capacity of 205.5 mAh/g at 0.1 C, further indicating the superior application potential in commercial utilization.

Withdrawn: Percutaneous Multi-angle Thread Needle for Two- or Three-part Unstable Fractures of the Proximal Humerus in Older Population

Since the authors are not responding to the editor's request to fulfill the editorial requirement, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham editorial policy on article withdrawal can be found at https://benthamscience.com/journal/33/editorialpolicy BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication, the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Se-induced defective carbon nanotubes promoting superior kinetics and electrochemical performance in Na3V2(PO4)3 for half and full Na ion cells.

Na3V2(PO4)3 (NVP), with unique Na super ionic conductivity (NASICON) framework, has become an prospective cathode material. However, the low electronic conductivity and poor structural stability limit its further development. Currently, the optimized carbon nanotubes (CNTs) by selenium doping are utilized to modify NVP system for the first time. Notably, the introduction of selenium in CNTs promotes to generate more defects, resulting in abundant active sites for the de-intercalation of Na+ to achieve more pseudocapacitance. Moreover, the newly formative C-Se bonds possess much stronger bond energy than the original CC (586.6 KJ mol-1 vs 377.4 KJ mol-1) bonds. The structure arrangement of the original CNTs is significantly improved by the doped selenium element, indicating that an enhanced carbon skeleton could be obtained to sustain the structural stability of NVP system. Furthermore, the excess selenium can be doped into the bulk of NVP crystal to replace of partial oxygen. Due to the larger ionic of Se2- (1.98 Å vs 1.4 Å of O2-), the VSe6 group has larger framework, which provides a broadened pathway for Na+ migration to improve the kinetic characteristics. Accordingly, the modified NVP@CNTs:Se = 1:1 sample exhibits superior rate capability and cyclic performance. It reveals high capacities of 78.6 and 76.5 mAh/g at 20 and 60C, maintaining 65.4 and 53.8 mAh/g after 5000 and 7000 cycles with high capacity retention of 84.49 % and 70.32 %, respectively. The assembled NVP@CNTs:Se = 1:1//CHC full cell delivers a high value of 153.6 mAh/g, suggesting the optimized sample also behaves excellent application potentials.

Enhanced performance of Sn-doped Na3V2(PO4)3 with CNT integration for high-efficiency sodium-ion batteries.

The development of Na3V2(PO4)3 (NVP) has been severely hindered by low conductivity and unstable crystal structure. A simultaneously optimized strategy of Na-rich and Sn substitution is proposed for the first time. SnX-NVP@CNTs with different doping gradients are successfully prepared by the facile sol-gel method. Notably, more hole carriers can be generated by introducing Sn2+, thus improving its electron transport efficiency. In addition, since Sn2+ ions have a larger ion radius; when replacing V3+ ions at pillar positions, the lattice spacing can be enlarged to improve the structural stability of electrode materials. Meanwhile, it is beneficial to the movement of deep-level Na+ ions and improves the utilization rate of electrode materials. Moreover, to achieve charge compensation, it is necessary to introduce excess Na+ to the Sn-doped NVP system, which will increase the number of Na+ involved in the deintercalation process and improve its reversible capacity. Furthermore, the dense coating of CNTs can form an efficient conductive network structure, which improves the electron transport rate and inhibits the accumulation of active grains to accelerate Na+ diffusion. Under the synergistic adjustment of Sn2+ doping and CNTs enwrapping, the prepared Sn0.07-NVP@CNTs exhibit a high reversible capacity of 115.1 mAh/g at 0.1C, and the capacity retention rate reaches 89.35 % after 2000 cycles at 10C. Even after 10,000 cycles at 60C, its reversible capacity dropped from the initial 75.9 to 51.3 mAh/g, with a capacity loss of only 0.003 % per cycle. Besides, the Sn0.07-NVP@CNTs//CHC full battery releases a capacity of 139.9 mAh/g, highlighting its great potential for actual applications.

Chemical Evolution of Enzyme-Catalyzed Glycosylation.

ConspectusThe limited availability of structurally well-defined diverse glycans remains a major obstacle for deciphering biological functions as well as biomedical applications of carbohydrates. Despite tremendous progress that has been made in past decades, the synthesis of structurally well-defined complex glycans still represents one of the most challenging topics in synthetic chemistry. Chemical synthesis of glycans is a time-consuming and labor-intensive process that requires elaborate planning and skilled personnel. In contrast, glycosyltransferase-catalyzed enzymatic synthesis provides a more efficient, convenient, low-cost, and sustainable alternative to affording diverse and complex glycans. However, the existing methods are still insufficient to fulfill the increasing demand for specific synthetic glycan libraries necessary for functional glycomics research. This is mainly attributed to the inherent character of the glycan biosynthetic pathway. In nature, there are too many glycosyltransferases involved in the in vivo glycan synthesis, but only a small number of them are available for in vitro enzymatic synthesis. For instance, humans have over 200 glycosyltransferases, but only a few of them could be produced from the conventional bacterial expression system, and most of these membrane-associated enzymes could be overexpressed only in eukaryotic cells. Moreover, the glycan biosynthetic pathway is a nontemplate-driven process, which eventually ends up with heterogeneous glycan product mixtures. Therefore, it is not a practical solution for the in vitro enzymatic synthesis of complex glycans by simply copying the glycan biosynthetic pathway.In the past decade, we have tried to develop a simplified and transformable approach to the enzymatic modular assembly of a human glycan library. Despite the structural complexity of human glycans, the glycoinformatic analysis based on the known glycan structure database and the human glycosyltransferase database indicates that there are approximately 56 disaccharide patterns present in the human glycome and only 16 disaccharide linkages are required to account for over 80% of the total disaccharide fragments, while 35 disaccharide linkages are sufficient to cover over 95% of all disaccharide fragments of human glycome. Regardless of the substrate specificity, if one glycosyltransferase could be used for the synthesis of all of the same glycosidic linkages in human glycome, it will require only a few dozen glycosyltransferases for the assembly of entire human glycans. According to the glycobioinformatics analysis results, we rationally designed about two dozen enzyme modules for the synthesis of over 20 common glycosidic linkages in human glycome, in which each enzyme module contains a glycosyltransferase and a group of enzymes for the in situ generation of a nucleotide-activated sugar donor. By sequential glycosylation using orchestrated enzyme modules, we have completed the synthesis of over 200 structurally well-defined complex human glycans including blood group antigens, O-mannosyl glycans, human milk oligosaccharides, and others. To overcome the product microheterogeneity problem of enzymatic synthesis in the nontemplate-driven glycan biosynthetic pathway, we developed several substrate engineering strategies to control or manipulate the outcome of glycosyltransferase-catalyzed reactions for the precise synthesis of structurally well-defined isomeric complex glycans.

Simultaneous Mn and Cl doping on Na3V2(PO4)3 with high performance for full sodium-ion batteries.

Nowadays, the poor conductivity and unstable structure have become obstacles for the popularization of Na3V2(PO4)3 (NVP). In the current work, a dual-modified Mn0.1Cl0.3-NVP composite doped with Mn and Cl is prepared by a facile sol-gel method. When Mn2+ with a large ionic radius replaces small V3+, it can improve the stability of the NVP crystal structure. In addition, the replacement of V3+ by Mn2+ in a low valence state can generate redundant hole carriers, which is conducive to the rapid transport of electrons. The substitution of PO43- by Cl-, which is more electronegative, can reduce the impedance and facilitate the movement of Na+. Owing to the synergistic effect of Mn and Cl co-substitution, the structural stability of NVP was systematically enhanced, and the electron transfer and ion diffusion were effectively improved. Consequently, the optimized Mn0.1Cl0.3-NVP sample demonstrated superior electrochemical performance and kinetic properties. It exhibited a high reversible capacity of 109.2 mA h g-1 at 0.1C. Even at 15 and 30C, high discharge capacities of 70.3 mA h g-1 and 68.2 mA h g-1 were observed after 2000 cycles with capacity retention above 80%. Moreover, it delivered remarkable capacities of 77.1 and 73.4 mA h g-1 at 100 and 200C with retained capacity values of 50.3 and 47 mA h g-1, respectively, after 2000 cycles. Furthermore, the assembled Mn0.1Cl0.3-NVP//HC full cell delivered a high value of 94.7 mA h g-1 and lit LED bulbs, indicating its excellent application potential.

Comparison of plant diversity-carbon storage relationships along altitudinal gradients in temperate forests and shrublands.

Understanding the mechanisms underlying the relationship between biodiversity and ecosystem function (BEF) is critical for the implementation of productive and resilient ecosystem management. However, the differences in BEF relationships along altitudinal gradients between forests and shrublands are poorly understood, impeding the ability to manage terrestrial ecosystems and promote their carbon sinks. Using data from 37962 trees of 115 temperate forest and 134 shrubland plots of Taihang Mountains Priority Reserve, we analyzed the effects of species diversity, structural diversity, climate factors and soil moisture on carbon storage along altitudinal gradients in temperate forests and shrublands. We found that: (1) Structural diversity, rather than species diversity, mainly promoted carbon storage in forests. While species diversity had greater positive effect on carbon storage in shrublands. (2) Mean annual temperature (MAT) had a direct negative effect on forest carbon storage, and indirectly affected forest carbon storage by inhibiting structural diversity. In contrast, MAT promoted shrubland carbon storage directly and indirectly through the positive mediating effect of species diversity. (3) Increasing altitudinal gradients enhanced the structural diversity-carbon relationship in forests, but weakened the species diversity-carbon relationship in shrublands. Niche and architectural complementarity and different life strategies of forests and shrubs mainly explain these findings. These differential characteristics are critical for our comprehensive understanding of the BEF relationship and could help guide the differentiated management of forests and shrublands in reaction to environmental changes.

Comparison of stigmatizing views towards COVID-19 and mental disorders among adolescent and young adult students in China.

Objective: Infectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China. Methods: A total of 9,749 adolescents and young adults aged 15-24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views. Findings: The prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (ß = 0.025, p < 0.05), those without quarantine experience (ß = 0.035, p < 0.001), those with lower educational level (p < 0.001), those with lower family income (p < 0.01), and those with higher PTSD symptoms (ß = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income (p < 0.01), depression symptoms (ß = 0.056, p < 0.001), anxiety symptoms (ß = 0.051, p < 0.001), and mental health problems (ß = 0.027, p < 0.05). Conclusion: The stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions.

Safety and Efficacy of Tirofiban Bridging Therapy During a Hybrid Carotid Artery Stenting and Off-pump Coronary Artery Bypass Grafting Surgery: A Single-center Study.

PURPOSE: The optimal perioperative antithrombosis management for carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) hybrid surgeries remains unclear; however, a more aggressive antithrombotic therapy might be required after a hybrid CAS + CABG duo stent-related intimal injury or the use of protamine-neutralizing heparin. This study evaluated the safety and efficacy of tirofiban as a bridging therapy after a hybrid CAS + CABG surgery. METHODS: Between June 2018 and February 2022, a total of 45 patients undergoing a hybrid CAS + off-pump CABG surgery were divided into either the control group (standard dual antiplatelet therapy postsurgery, n = 27) or the tirofiban group (tirofiban bridging + dual antiplatelet therapy, n = 18). The 30-day outcome was compared between the 2 groups, and the primary end points included stroke, postoperative myocardial infarction, and death. FINDINGS: Two patients (7.41%) from the control group experienced a stroke. There was a trend toward a lower rate of composite end points, including stroke, postoperative myocardial infarction, and death, within the tirofiban group that did not reach statistical significance (0% vs 11.1%; P = 0.264). The need for a transfusion was similar between the 2 groups (33.33% vs 29.63%; P = 0.793). There were no major bleeding events in the 2 groups. IMPLICATIONS: Tirofiban bridging therapy was safe, with a trend toward reducing the risk of ischemic events after a hybrid CAS + off-pump CABG surgery. Tirofiban might be a feasible periprocedural bridging protocol in high-risk patients.

Short and long-term outcomes after off-pump coronary endarterectomy stratified by different target vessels.

BACKGROUND: The efficacy of off-pump coronary endarterectomy (CE) has been proven in patients with diffuse coronary artery disease (DCAD). However, the clinical benefits of of-pump CE stratified by different target vessels remain controversial. This retrospective study assessed the effect of the territory and number of CE on short- and long-term outcomes of DCAD. METHODS: From January 2012 to December 2014, 246 patients undergoing off-pump coronary artery bypass grafting (OPCABG) + CE were included. The patients were grouped by the territory and number of CE. The primary endpoints were postoperative acute myocardial infarction (PMI) and long-term major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Sixty-five patients (26.42%) were in the left anterior descending branch (LAD) group (CE on LAD), 134(54.47%) in the right coronary artery (RCA) group (CE on RCA), and 47(19.10%) in the multi-vessels group. PMI in the LAD group, RCA group, and multi-vessels group were 3.08%, 6.72%, and 14.89%, respectively (P = 0.08). Multi-vessels CE (OR = 9.042, 95%CI 2.198-37.193, P = 0.002), CE-plaque length ≥ 3 cm (OR = 6.247, 95%CI 2.162-18.052, P < 0.001), and type 2 diabetes mellitus (2DM) (OR = 4.072, 95%CI 1.598-10.374, P = 0.003) were independent risk factors of PMI. The long-term (mean 76 months) MACCE in the LAD group, RCA group, and multi-vessels group were 13.85%, 17.91%, and 10.64%, respectively (P = 0.552). Cox analysis indicated that PMI (HR = 7.113, 95%CI 3.129-16.171, P < 0.001) and Age ≥ 65 years (HR = 2.488, 95%CI 1.214-5.099, P = 0.013) increased the risk of long-term MACCE. CONCLUSIONS: Multi-vessel CE and CE-plaque length ≥ 3 cm significantly increased risk of PMI after OPCABG + CE, but the territory and number of CE did not affect long-term MACCE.

Nutrient reallocation between stem and leaf drives grazed grassland degradation in inner Mongolia, China.

BACKGROUND: Decline in height and aboveground biomass of the plant community are critical indicators of grassland ecosystem degradation. Nutrient reallocation induced by grazing occurs among different organs, which balances the trade-off between growth and defense. However, it is not yet clear how nutrient reallocation strategies affect plant community structure and functions in grazed grasslands. A grazing experiment was conducted in a typical steppe in Inner Mongolia, China. We investigated plant community characteristics and measured plant functional traits of dominant species (Leymus chinensis and Cleistogenes squarrosa) at individual and population levels. Carbon (C), nitrogen (N), phosphorus (P), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn) concentrations of stem and leaf in the two species were also determined. RESULTS: N, P, Cu, Fe, Mn, and Zn concentrations in leaves and stems of L. chinensis and C. squarrosa significantly increased with grazing intensity, and microelements (Cu, Fe, Mn, and Zn) were more sensitive to grazing. The nutrient slopes of macro- and microelements in leaves were significantly higher than those in stems under grazing, indicating that nutrient resources were preferentially allocated to leaves and enhanced the compensatory growth of leaves in the grazed grassland. With increasing grazing intensity, the aboveground biomass of stems and leaves in the two species significantly decreased, but leaf to stem ratio increased at the individual level, indicating that plants preferentially allocated biomass to leaves under grazing. The increase in leaf to stem ratio due to nutrient reallocation between the two organs significantly reduced height and aboveground biomass at population and community levels, driving grassland ecosystem degradation. CONCLUSION: Our study revealed the driving forces of community structure and function degradation in grazed grasslands from the perspective of nutrient resource allocation, and provided insights into plant adaptation strategies to grazing.

A Redox-Controlled Substrate Engineering Strategy for Site-Specific Enzymatic Fucosylation.

Fucosylation is one of the most common modifications of oligo-N-acetyllactosamine (oligo-LacNAc) glycans. However, none of known fucosyltransferases (FucTs) could install the α1,3-linked fucose to the oligo-LacNAc substrates in a site-specific manner. Here, we report a facile and general redox-controlled substrate engineering strategy for the site-specific α1,3-fucosylation of complex glycans containing multiple LacNAc units. This strategy takes advantage of an operationally simple oxidation enzyme module by using galactose oxidase (GOase) to convert the LacNAc unit into oxidized C6'-aldehyde LacNAc sequence, which is not a good substrate for recombinant α1,3-FucT from Helicobacter pylori strain 26695 (Hpα1,3FucT), enabling the site-specific α1,3-fucosylation at intact LacNAc sites. The general applicability and robustness of this strategy were demonstrated by the synthesis of a variety of structurally well-defined fucosides of linear and branched O- and N-linked glycans.

Constructing p-type substitution induced by Ca2+ in defective Na3V2-xCax(PO4)3/C wrapped with conductive CNTs for high-performance sodium-ion batteries.

Na3V2(PO4)3 (NVP), with a high tap density, is considered a prospective cathode material due to its low cost, ideal specific capacity and cycling stability. However, its low ionic/electronic conductivity has become the main factor hindering its development. In the current work, a dual modification strategy has been proposed to optimize NVP, which is successfully achieved via a facile sol-gel method. The addition of partial Ca2+ with low valence at the V3+ site produces favorable p-type substitution in the pristine NVP bulk, generating beneficial hole carriers in the electronic structure to accelerate the migration rate of Na+. Moreover, the doped Ca2+ with a larger ionic radius (1.03 Å vs. 0.64 Å of V3+) can have a pillar effect to support the cell structure, improving the structural stability of NVP. Meanwhile, the larger radius of Ca2+ contributes to the expansion of the lattice spacing, significantly facilitating the diffusion efficiency of Na+ to optimize the diffusion kinetics. Besides, the evenly coated carbon layers derived from the excess carbon resources combine with the enwrapped carbon nanotubes to construct a highly conductive network to enhance the transportation of electrons. Notably, the modified Ca0.04-NVP@CNTs electrode exhibits a high capacity of 117.4 mA h g-1 at 0.1 C, while that of NVP is only 69.4 mA h g-1. Moreover, it delivers an initial capacity of 110.1 mA h g-1 at 1 C and the mass loss rate per lap is only 0.01%. At 5 C, the initial capacity of Ca0.04-NVP@CNTs is 104.3 mA h g-1 while that of NVP is only 75.9 mA h g-1. Interestingly, it exhibits excellent cycling stability at 50 C; the initial capacity is 75.7 mA h g-1 and the capacity retention is around 99% after 4000 cycles.

Adventitial Collagen Cross-Linking by Glutaraldehyde Reinforcing Human Saphenous Vein - Implication for Coronary Artery Bypass Grafting.

INTRODUCTION: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. METHODS: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. RESULTS: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P<0.05). After adventitial cross-linking, the collagen I fibres of the vein remarkably presented with compact and nonporous arrangement. In the high-stretch region (stretch ratio 1.4-1.8), the Young's elastic modulus of stress-stretch ratio curve in cross-linked SVs was larger than that in native SVs (13.88 vs. 5.83, P<0.05). The cross-linked SVs had a lower extent of endothelial denudation without fibre fracture during high-pressure distension than native SVs. Comparing with the non-cross-linked SVs, the percentage of endothelial nitric oxide synthase staining length on the endothelium of cross-linked SVs was significantly preserved after high-pressure distension (85.2% vs. 64.7%, P<0.05). CONCLUSION: Adventitial collagen cross-linking by glutaraldehyde reinforced venous wall by increasing stiffness and decreasing extensibility of SVs and mitigated the endothelial damage under high-pressure distension.