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1.
Angew Chem Int Ed Engl ; 63(18): e202401773, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38429971

RESUMO

Organic electrochemical transistors (OECTs) rely on both efficient ionic doping/de-doping process and carrier transport in the mixed ionic-electronic channel under the modulation of gate bias. Moreover, channels that hold photopatterning capability are highly desired to minimize parasitic capacitance and simplify the fabrication process/cost. However, yielding photo-patternable channels with both precise/robust patterning capability and controllable ionic-electronic coupling is still challenging. Herein, double-end trifluoromethyl diazirines (DtFDA) with different chain lengths are introduced in the OECT channel to act as both photo-crosslinker and medium to regulate ionic-electronic transport. Specifically, high-resolution patterns with a minimum line width/gap of 2 µm are realized in p(g2T-T) or Homo-gDPP based channels by introducing DtFDA. Maximum transconductances of 68.6 mS and 81.6 mS, current on/off ratio of 106 and 107 (under a drain voltage of only ±0.1 V), are achieved in p- and n-type vertical OECTs (vOECTs), respectively, along with current densities exceeding 1 kA cm-2 and good cycling stability of more than 100,000 cycles (2000 seconds). This work provides a new and facile strategy for the fabrication of vOECT channels with high resolution and high performance via the introduction of a simple and efficient crosslinker.

2.
PLoS One ; 19(3): e0299805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512903

RESUMO

The automatic cutting of coal and rock surface morphology modeling based on the actual geological environment of coal mine underground excavation and mining is of great significance for improving the surface quality of coal and rock after cutting and enhancing the safety and stability of advanced support. To this end, using the principle of coordinate transformation, the kinematic trajectory of the cutting head of the tunneling machine is established, and the contour morphology of the cutting head under variable cutting technology is obtained. Then, based on the regenerative vibration theory of the cutting head, a dynamic model of the cutting head coal wall is established, and the coordinate relationship of the cutting head in the tunnel coordinate system under vibration induction is analyzed. Based on fractal theory and Z-MAP method, a simulation method for the surface morphology of coal and rock after cutting is proposed, which is driven by the cutting trajectory Under the coupling effect of cutting vibration induction and random fragmentation of coal and rock, simulation of the surface morphology of comprehensive excavation tunnels was conducted, and relevant experiments were conducted to verify the results. A 1:3 similarity experimental model of EBZ160 tunneling machine was used to build a cutting head coal and rock system cutting experimental platform for comparative experiments of cutting morphology. Furthermore, statistical methods were used to compare and evaluate the simulated roof with the actual roof. The results show that the relative errors between the maximum range of peaks and valleys, the peak skewness coefficient of height standard deviation, and the kurtosis coefficient of the actual roof are 1.3%, 24.5%, 16%, and 2.9%, respectively. Overall, this indicates that the surface morphology distribution characteristics of the simulated roof and the actual roof are similar, verifying the effectiveness of the modeling and simulation method proposed in this paper, and providing theoretical support for the design and optimization of advanced support in the future.


Assuntos
Carvão Mineral , Traumatismos Craniocerebrais , Humanos , Simulação por Computador , Meio Ambiente , Fractais
3.
Ann Med Surg (Lond) ; 86(2): 1152-1155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333290

RESUMO

Introduction and importance: Abdominal cocoon syndrome (ACS), as a rare cause of mechanical intestinal obstruction, can be divided into primary/idiopathic vs. secondary type. The primary ACS is often asymptomatic and only diagnosed in exploratory laparotomy. The major treatment of surgery can be challenging. Since the gut wall and peritoneum are densely adhered, gut perforation might occur during adhesiolysis. Thus, it is important to have an experienced surgeon to perform the surgery. Case presentation: The authors present a primary ACS case of a 50-year-old man. The patient demonstrated an unbearable upper abdominal pain upon admission. A computed tomography (CT) scan showed a severe bowel obstruction. An exploratory laparotomy was indicated, leading to the diagnosis of ACS, which was considered idiopathic after ruling out secondary factors. An adhesiolysis was performed successfully. Note that the entire intestine measured was only 2.1 m during the surgery. There was no post-surgical complication. The patient was recovered uneventfully. Clinical discussion: The aetiology of primary ACS is unknown. The incidence is comparatively low and considered equal between men and women. As a rare cause of gut obstruction, the suspicion of the diagnosis should be strengthened. Surgery including adhesiolysis and bowel resection remains the major treatment. If adhesiolysis fails, bowel resection will be inevitable. The knowledge and experience of surgeon will be tested. Conclusion: The aetiology of primary ACS should be further explored. And the differential diagnosis of bowel obstruction should cover ACS in order for the surgeon to be prepared before surgery.

4.
Int J Biol Macromol ; 263(Pt 1): 130271, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373570

RESUMO

Overuse of insecticides has accelerated the evolution of insecticide resistance and created serious environmental concerns worldwide, thus incentivizing development of alternative methods. Bacillus thuringiensis (Bt) is an insecticidal bacterium that has been developed as a biopesticide to successfully control multiple species of pests. It operates by secreting several insect toxins such as Cry1Ac. However, metabolic resistance based on ATP-binding cassette (ABC) transporters may play a crucial role in the development of metabolic resistance to Bt. Here, we characterized an ABCG gene from the agricultural pest Plutella xylostella (PxABCG3) and found that it was highly expressed in a Cry1Ac-resistant strain, up-regulated after Cry1Ac protoxin treatment. Binding miR-8510a-3p to the coding sequence (CDS) of PxABCG3 was then confirmed by a luciferase reporter assay and RNA immunoprecipitation. miR-8510a-3p agomir delivery markedly reduced PxABCG3 expression in vivo and consequently decreased the tolerance of P. xylostella to Cry1Ac, while reduction of miR-8510a-3p significantly increased PxABCG3 expression, accompanied by an increased tolerance to Cry1Ac. Our results suggest that miR-8510a-3p could potentially be used as a novel molecular target against P. xylostella or other lepidopterans, providing novel insights into developing effective and environmentally friendly pesticides.


Assuntos
Bacillus thuringiensis , Inseticidas , MicroRNAs , Mariposas , Animais , Mariposas/metabolismo , Larva/genética , Endotoxinas/genética , Endotoxinas/metabolismo , Toxinas de Bacillus thuringiensis/metabolismo , Bacillus thuringiensis/química , Inseticidas/farmacologia , Inseticidas/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/farmacologia , Proteínas Hemolisinas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
5.
Adv Mater ; : e2311424, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38325426

RESUMO

Apart from Li4 Ti5 O12 , there are few anode substitutes that can be used in commercial high-power lithium-ion batteries. Orthorhombic T-Nb2 O5 has recently been proven to be another substitute anode. However, monoclinic B-Nb2 O5 of same chemistry is essentially inert for lithium storage, but the underlying reasons are unclear. In order to activate the "inert" B-Nb2 O5 , herein, nanoporous pseudocrystals to achieve a larger specific capacity of 243 mAh g-1 than Li4 Ti5 O12 (theoretical capacity: 175 mAh g-1 ) are proposed. These pseudocrystals are rationally synthesized via a "shape-keep" topological microcorrosion process from LiNbO3 precursor. Compared to pristine B-Nb2 O5 , experimental investigations reveal that B-Nb2 O5- x delivers ≈3000 times higher electronic conductivity and tenfold enhanced Li+ diffusion coefficient. An ≈30% reduction of energy barrier for Li-ion migration is also confirmed by the theoretical calculations. The nanoporous B-Nb2 O5- x delivers unique ion/electron transport channels to proliferate the reversible and deeper lithiation, which activate the "inert" B-Nb2 O5 . The capacitive-like behavior is observed to endow B-Nb2 O5- x ultrafast lithium storage ability, harvesting 136 mAh g-1 at 100 C and 72 mAh g-1 even at 250 C, superior to Li4 Ti5 O12 . Pouch-type full cells exhibit the energy density of ≈251 Wh kg-1 and ultrahigh power density up to ≈35 kW kg-1 .

6.
Phys Chem Chem Phys ; 26(9): 7269-7275, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38193864

RESUMO

On the basis of variable-temperature single-crystal X-ray diffraction, rotational energy barrier analysis, variable-temperature/frequency dielectric response, and molecular dynamics simulations, here we report a new crystalline supramolecular rotor (CH3NH3)(18-crown-6)[CuCl3], in which the (H3C-NH3)+ ion functions as a smallest dual-wheel rotator showing bisected rotation dynamics, while the host 18-crown-6 macrocycle behaves as a stator that is not strictly stationary. This study also provides a helpful insight into the dynamics of ubiquitous -CH3/-NH3 groups confined in organic or organic-inorganic hybrid solids.

7.
J Colloid Interface Sci ; 660: 545-554, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266336

RESUMO

Thermal runaway is a hazardous risk, occurring more readily in high-energy-density lithium-ion batteries (LIBs), which leads to a rapid temperature rise and even combustion or explosion when using flammable electrolyte systems. Flame retardants (FRs), such as trimethyl phosphate (TMPa) and triethyl phosphate (TEP), are commonly utilized due to their effective flame suppression, low toxicity, and excellent thermal stability. However, the lack of in-depth understanding of the flame retardancy mechanism and solid electrolyte interphase (SEI) formation process has made the development of functional electrolytes difficult at present. In this study, we clarified the flame retardancy and interfacial reaction mechanisms of low-flammable TMPa localized high-concentration electrolytes (LHCE) using hybrid ab initio and reactive force field (HAIR) schemes. Long-term HAIR simulation reveals that phosphorous radicals produced by the decomposition of TMPa capture carbon radicals, encouraging their polymerization into low-flammable oligomers, while fluorine-containing solvents in the electrolyte capture hydrogen radicals and produce nonflammable hydrofluoric acid (HF). This synergistic flame retardancy mechanism provides essential atomic-level insights for the rational design of high-safety electrolytes in the future.

8.
Adv Sci (Weinh) ; 11(13): e2306248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38251411

RESUMO

Protein degradation techniques, such as proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self-assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof-of-concept study, vascular endothelial growth factor receptor (VEGFR)-binding peptides and mannose-6 phosphate (M6P) moieties into a self-assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin-2 (ANG-2) gene as cross-linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR-2 and ANG-2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age-related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.


Assuntos
Ácidos Nucleicos , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/genética , Regulação para Baixo , RNA Interferente Pequeno/genética , Hidrogéis
9.
Adv Mater ; 36(6): e2309637, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985136

RESUMO

Molybdenum disulfide (MoS2 ) with high theoretical capacity is viewed as a promising anode for sodium-ion batteries but suffers from inferior rate capability owing to the polaron-induced slow charge transfer. Herein, a polaron collapse strategy induced by electron-rich insertions is proposed to effectively solve the above issue. Specifically, 1D [MoS] chains are inserted into MoS2 to break the symmetry states of 2D layers and induce small-polaron collapse to gain fast charge transfer so that the as-obtained thermodynamically stable Mo2 S3 shows metallic behavior with 107 times larger electrical conductivity than that of MoS2 . Theoretical calculations demonstrate that Mo2 S3 owns highly delocalized anions, which substantially reduce the interactions of Na-S to efficiently accelerate Na+ diffusion, endowing Mo2 S3 lower energy barrier (0.38 vs 0.65 eV of MoS2 ). The novel Mo2 S3 anode exhibits a high capacity of 510 mAh g-1 at 0.5 C and a superior high-rate stability of 217 mAh g-1 at 40 C over 15 000 cycles. Further in situ and ex situ characterizations reveal the in-depth reversible redox chemistry in Mo2 S3 . The proposed polaron collapse strategy for intrinsically facilitating charge transfer can be conducive to electrode design for fast-charging batteries.

10.
Angew Chem Int Ed Engl ; 63(4): e202315282, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38032360

RESUMO

Recently, therapeutic cancer vaccines have emerged as promising candidates for cancer immunotherapy. Nevertheless, their efficacies are frequently impeded by challenges including inadequate antigen encapsulation, insufficient immune activation, and immunosuppressive tumor microenvironment. Herein, we report a three-in-one hydrogel assembled by nucleic acids (NAs) that can serve as a vaccine to in situ trigger strong immune response against cancer. Through site-specifically grafting the chemodrug, 7-ethyl-10-hydroxycamptothecin (also known as SN38), onto three component phosphorothioate (PS) DNA strands, a Y-shaped motif (Y-motif) with sticky ends is self-assembled, at one terminus of which an unmethylated cytosine-phosphate-guanine (CpG) segment is introduced as an immune agonist. Thereafter, programmed cell death ligand-1 (PD-L1) siRNA that performs as immune checkpoint inhibitor is designed as a crosslinker to assemble with the CpG- and SN38-containing Y-motif, resulting in the formation of final NA hydrogel vaccine. With three functional agents inside, the hydrogel can remarkably induce the immunogenic cell death to enhance the antigen presentation, promoting the dendritic cell maturation and effector T lymphocyte infiltration, as well as relieving the immunosuppressive tumor environment. When inoculated twice at tumor sites, the vaccine demonstrates a substantial antitumor effect in melanoma mouse model, proving its potential as a general platform for synergistic cancer immunotherapy.


Assuntos
Melanoma , Ácidos Nucleicos , Vacinas , Animais , Camundongos , Hidrogéis/metabolismo , Ácidos Nucleicos/metabolismo , Células Dendríticas/metabolismo , Imunoterapia , Vacinação , Microambiente Tumoral , Linhagem Celular Tumoral , Antígeno B7-H1/metabolismo
11.
Sci Rep ; 13(1): 19236, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935750

RESUMO

A new type of parallel operation unit for excavating and supporting anchors is proposed to address the issue of imbalanced excavation anchor ratio in coal mines. By equipping a straddle type anchoring drilling rig group, the synchronous parallel and fast operation mode for excavating and supporting anchors is achieved; Consider the problem of poor drilling stability of drill pipes in coal mines due to the coupling vibration between surrounding rock and anchoring equipment. Firstly, taking the multi drilling rig anchoring system as the research object, considering the influence of the equipment itself as an influencing factor on the vibration of the drill pipe, a dynamic model of the system is constructed using Lagrangian equations, and analytical solutions for the vibration displacement of each mass block are obtained; In order to more intuitively represent the vibration process of the drill pipe, Ansys is used to conduct modal analysis on the key components of the anchoring drilling rig system, and obtain the natural frequencies and vibration modes of each order of the key components; Using Adams to solve the rigid flexible coupling dynamic model of the anchoring drilling rig system, the vibration response laws of the drill pipe under different operating states were obtained. Secondly, Abaqus was used to simulate the drilling process of the drill pipe and obtain the vibration response law generated by the interaction between the drill pipe and the surrounding rock; The results indicate that the anchoring equipment has a greater impact on the vibration of the drill pipe, and the surrounding rock has a more stable impact on the vibration of the drill pipe. Due to the short body and large span structure of the anchoring system crossbeam expansion frame, the vibration response of the drill pipe is significantly greater than that of the retracted state of the drilling rig due to being in an unstable cantilever state when the drilling rig is extended. The theoretical reliability of the vibration response law of the drill pipe under different states has been further verified through drilling experiments of the anchoring system prototype. The relevant theories can provide a theoretical basis for the implementation of automatic anchoring technology in the anchoring system.

12.
Sci Rep ; 13(1): 18078, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872246

RESUMO

The cutting process of the cantilever tunneling machine mainly generates excitation through the cutting motor or the hydraulic cylinder driven by the hydraulic system. Regardless of the driving method, the frequency width of the excitation system is limited, difficult to control, and the excitation effect is poor. Therefore, in order to improve excavation efficiency, the excitation system parallel to the original cutting and rotating system is designed. Based on the excitation characteristics caused by alternating fluid flow, the core component of the excitation system, hydraulic exciter, is designed, and the dynamics and dynamic characteristics of the excitation system are analyzed. Based on AMESim software, analyze the impact of factors such as pump displacement, excitation frequency, and pipeline parameters on the operational performance of the electro-hydraulic vibration cutting system, and conduct experimental verification by building a cutting test bench. The experimental results show that as the inner diameter of the pipeline increases, the fluctuation at the acceleration turning point decreases in each cycle and approaches the peak faster. As the excitation frequency increases, the cutting acceleration of the electro-hydraulic excitation cutting system decreases first and then increases, verifying the accuracy of the simulation results. In the experiment, it was found that the acceleration transformation range of the cutting head of the excitation system is the smallest and most stable when the excitation frequency is 30 Hz. In order to verify that the excitation frequency of 30 Hz is the optimal frequency, further contact force tests were conducted on the cutting teeth. It was found that when the hydraulic excitation system adds a 30 Hz excitation frequency, the contact force on the cutting teeth is the smallest. It is more conducive to reducing the damage and wear of the cutting head, and the cutting effect of the cutting head is more obvious. The research results are beneficial for improving the cutting performance of the electro-hydraulic excitation cutting system, providing theoretical support for the selection of cutting parameters for excavation machinery and hydraulic excitation, and improving the existing theoretical system for active excitation cutting vibration analysis of excavation machines.

13.
Sci Rep ; 13(1): 16781, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798447

RESUMO

High-efficiency rock breaking technology is an important problem to be solved urgently in deep mining. The existing auxiliary rock breaking technology for coal mine excavation has problems such as polluting coal, high requirements for tool materials, and difficulty in subsequent washing. In this paper, an active excitation cutting system for rotary cylinder of cantilever roadheader based on alternating valve is proposed. According to the classical calculation formula of cutting load of roadheader, considering the stiffness-damping characteristics of cutting part and cutting cylinder, the simulation algorithm of cutting load is compiled based on MATLAB simulation analysis software. The excitation cutting experiments of different cutting depths are carried out on the cutting test bench, and compared with the simulation algorithm of cutting load. Taking the cutting load as the discriminant index, the influence of oil supply pressure and excitation frequency of rotary cylinder on the cutting load is analyzed based on the simulation algorithm of cutting load. The results show that the error between the simulation results and the experimental results of the active excitation state is less than 12%, and the two are in good agreement. Under the condition of 30 HZ, when the excitation amplitude is 8 Mpa, 10 Mpa, 12 Mpa, 14 Mpa, when the rotary cylinder excitation amplitude is 10 Mpa, the minimum is 131.42 KN. Compared with the rotary cylinder excitation amplitude under the condition of 10 Mpa, when the excitation frequency is 30 HZ, 35 HZ, 40 HZ, 45 HZ, when the excitation frequency is 40 HZ, the minimum is 83.08 KN, indicating that changing the excitation amplitude or oil supply pressure of the rotary cylinder is helpful to adjust the cutting performance.

14.
Am J Transl Res ; 15(8): 5276-5283, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692929

RESUMO

OBJECTIVE: To examine the efficacy of immune checkpoint inhibitors along with chemotherapy in non-small cell lung cancer (NSCLC) and the effect on adverse reactions and serum tumor markers. METHODS: Data of 112 NSCLC patients admitted to Geriatric respiratory department, Xi'an International Medical Center Hospital from February 2018 to March 2021 were analyzed retrospectively. Among them, 54 patients treated with concurrent chemotherapy were labeled as the control group (CG), and 58 patients treated with PD-1/PD-L1 inhibitors in addition to chemotherapy were the observation group (OG). The two groups were compared in terms of immune function indexes, therapeutic efficacy, incidence of adverse reactions, 1-year survival rate, serum tumor markers before and after treatment, and independent risk factors affecting patients' prognosis. RESULTS: Compared to the CG, the OG exhibited significantly better therapeutic efficacy. The levels of IgG, IgA and IgM 6 months after treatment were significantly higher in both groups than those before treatment, and the elevations in the OG were more evident than those in the CG, and the OG demonstrated markedly lower Recombinant Cytokeratin Fragment Antigen 21-1 (CYFRA21-1), Carcinoembryonic antigen (CEA) and Carbohydrate antigen 125 (CA125) levels after treatment than the CG did. Between the two groups, there was no significant difference identified in the incidence of adverse reactions, but the OG was observed to have much higher 1-year survival rate. The pathological stage, differentiation and treatment regimen were independent risk factors affecting patients' prognosis. CONCLUSION: For NSCLC patients, the adoption of PD-1/PD-L1 inhibitors following chemoradiotherapy shows potential in enhancing clinical efficacy, boosting patients' immune function, and improving long-term survival rates, with premising safety profile.

15.
J Phys Chem Lett ; 14(36): 8009-8015, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37651131

RESUMO

Free accessible confined space and loose interaction are crucial for most solid-state ionic motions. Here, by using a near-spherical anion and a disc-shaped ammonium as two distinct but rigid building blocks, we report a new ionic crystal, (HMIm)3[La(NO3)6] (HMIm = 1-methyl-1H-imidazol-3-ium), in which the different confined spaces of three (HMIm)+ ions are fine-tuned over a broad temperature range. This effect can be utilized to modulate the dipolar polarization across a wide temperature/frequency range. Additionally, small-scale substitution of (HMIm)+ by its isomer of almost identical shape/size affords molecular solid solutions, which can further tune the dipolar polarization by varying the doping ratio. It is revealed that the differences in dipole moment and hydrogen bond rather than that of shape/size lead to a distorted crystalline environment for these solid solutions. Overall, we provide an exceptional model for understanding and regulating the dipole motion of polar aromatic molecules/ions in a crystalline environment.

16.
Nat Chem ; 15(12): 1705-1714, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37653229

RESUMO

Molecules that covalently engage target proteins are widely used as activity-based probes and covalent drugs. The performance of these covalent inhibitors is, however, often compromised by the paradox of efficacy and risk, which demands a balance between reactivity and selectivity. The challenge is more evident when targeting protein-protein interactions owing to their low ligandability and undefined reactivity. Here we report sulfur(VI) fluoride exchange (SuFEx) in vitro selection, a general platform for high-throughput discovery of covalent inhibitors from trillions of SuFEx-modified oligonucleotides. With SuFEx in vitro selection, we identified covalent inhibitors that cross-link distinct residues of the SARS-CoV-2 spike protein at its protein-protein interaction interface with the human angiotensin-converting enzyme 2. A separate suite of covalent inhibitors was isolated for the human complement C5 protein. In both cases, we observed a clear disconnection between binding affinity and cross-linking reactivity, indicating that direct search for the aimed reactivity-as enabled by SuFEx in vitro selection-is vital for discovering covalent inhibitors of high selectivity and potency.


Assuntos
Fluoretos , Enxofre , Humanos , Fluoretos/farmacologia , Fluoretos/química , Enxofre/química , Glicoproteína da Espícula de Coronavírus , Proteínas
17.
Nanomaterials (Basel) ; 13(13)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37446520

RESUMO

In recent times, magnetic resonance imaging (MRI) has emerged as a highly promising modality for diagnosing severe diseases. Its exceptional spatiotemporal resolution and ease of use have established it as an indispensable clinical diagnostic tool. Nevertheless, there are instances where MRI encounters challenges related to low contrast, necessitating the use of contrast agents (CAs). Significant efforts have been made by scientists to enhance the precision of observing diseased body parts by leveraging the synergistic potential of MRI in conjunction with other imaging techniques and thereby modifying the CAs. In this work, our focus is on elucidating the rational designing approach of CAs and optimizing their compatibility for multimodal imaging and other intelligent applications. Additionally, we emphasize the importance of incorporating various artificial intelligence tools, such as machine learning and deep learning, to explore the future prospects of disease diagnosis using MRI. We also address the limitations associated with these techniques and propose reasonable remedies, with the aim of advancing MRI as a cutting-edge diagnostic tool for the future.

18.
World J Emerg Med ; 14(3): 179-185, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152526

RESUMO

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

19.
World J Gastroenterol ; 29(16): 2502-2514, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37179587

RESUMO

BACKGROUND: Bacteremia, which is a major cause of mortality in patients with acute cholangitis, induces hyperactive immune response and mitochondrial dysfunction. Presepsin is responsible for pathogen recognition by innate immunity. Acylcarnitines are established mitochondrial biomarkers. AIM: To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage. METHODS: Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018. Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry, respectively. RESULTS: The concentrations of presepsin, procalcitonin, short- and medium-chain acylcarnitines increased, while long-chain acylcarnitines decreased with the severity of acute cholangitis. The areas under the receiver operating characteristic curves (AUC) of presepsin for diagnosing moderate/severe and severe cholangitis (0.823 and 0.801, respectively) were greater than those of conventional markers. The combination of presepsin, direct bilirubin, alanine aminotransferase, temperature, and butyryl-L-carnitine showed good predictive ability for biliary drainage (AUC: 0.723). Presepsin, procalcitonin, acetyl-L-carnitine, hydroxydodecenoyl-L-carnitine, and temperature were independent predictors of bloodstream infection. After adjusting for severity classification, acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality (hazard ratio 14.396; P < 0.001) (AUC: 0.880). Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine. CONCLUSION: Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage. Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis. Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.


Assuntos
Colangite , Sepse , Humanos , Pró-Calcitonina , Acetilcarnitina , Biomarcadores , Sepse/diagnóstico , Carnitina , Colangite/diagnóstico , Colangite/complicações , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Drenagem , Proteína C-Reativa/análise
20.
J Am Chem Soc ; 145(12): 6853-6860, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36939742

RESUMO

Adsorptive separation of propylene (C3H6) from propane (C3H8), which could deal with energy-intensive cryogenic distillation technologies, remains challenging due to their similar physiochemical properties. Herein, we present a pure silica zeolite with ordered silanols (OSs), whose crystallographic structure was unraveled by the advanced three-dimensional electron diffraction (3D ED), displaying the highly efficient separation of propylene from propane under ambient conditions. The 3D ED technique enables us to investigate its 8-ring pore opening transformation from the round one to the elliptical one during the removal of organic structure-directing agents. Such unique elliptical 8-ring pore openings can exclude larger-size propane and only adsorb propylene. Its C3H6/C3H8 separation performance is also confirmed by column breakthrough experiments, showing a high dynamic adsorption capacity of 53.36 cm3 g-1 for C3H6 but negligible C3H8 under ambient conditions. The dynamic capacity for C3H6 is superior to that of the well-known pure silica DDR-type zeolite (31.07 cm3 g-1). The density functional theory calculation demonstrates that the adsorbed propylene is distributed in the heart-shaped cavity and has a weak interaction with the OSs.

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