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1.
Cell ; 142(1): 52-64, 2010 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-20603014

RESUMEN

Cancer is influenced by its microenvironment, yet broader, environmental effects also play a role but remain poorly defined. We report here that mice living in an enriched housing environment show reduced tumor growth and increased remission. We found this effect in melanoma and colon cancer models, and that it was not caused by physical activity alone. Serum from animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and its genetic overexpression reduced tumor burden, whereas BDNF knockdown blocked the effect of EE. Mechanistically, we show that hypothalamic BDNF downregulated leptin production in adipocytes via sympathoneural beta-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Neoplasias del Colon/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Melanoma/metabolismo , Transducción de Señal , Medio Social , Adipocitos/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Neoplasias del Colon/genética , Neoplasias del Colon/fisiopatología , Genes APC , Vivienda para Animales , Hipotálamo/citología , Inmunocompetencia , Melanoma/genética , Melanoma/fisiopatología , Ratones , Ratones Endogámicos C57BL , Procesos Neoplásicos , Distribución Aleatoria , Receptores Adrenérgicos beta/metabolismo
2.
J Am Chem Soc ; 146(1): 782-790, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38165084

RESUMEN

The synthesis of single-crystal, one-dimensional (1D) polymers is of great importance but a formidable challenge. Herein, we report the synthesis of single-crystal 1D ladder polymers in solution by dynamic covalent chemistry. The three-dimensional electron diffraction technique was used to rigorously solve the structure of the crystalline polymers, unveiling that each polymer chain is connected by double covalent bridges and all polymer chains are packed in a staggered and interlaced manner by π-π stacking and hydrogen bonding interactions, making the crystalline polymers highly robust in both thermal and chemical stability. The synthesized single-crystal polymers possess permanent micropores and can efficiently remove CO2 from the C2H2/CO2 mixture to obtain high-purity C2H2, validated by dynamic breakthrough experiments. This work demonstrates the first example of constructing single-crystal 1D porous ladder polymers with double covalent bridges in solution for efficient C2H2/CO2 separation.

3.
J Am Chem Soc ; 146(23): 16194-16202, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38832699

RESUMEN

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

4.
J Am Chem Soc ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904843

RESUMEN

Flexible metal-organic materials (FMOMs) with stepped isotherms can offer enhanced working capacity in storage applications such as adsorbed natural gas (ANG) storage. Unfortunately, whereas >1000 FMOMs are known, only a handful exhibit methane uptake of >150 cm3/cm3 at 65 atm and 298 K, conditions relevant to ANG. Here, we report a double-walled 2-fold interpenetrated diamondoid (dia) network, X-dia-6-Ni, [Ni2L4(µ-H2O)]n, comprising a new azo linker ligand, L- (L- = (E)-3-(pyridin-4-yldiazenyl)benzoate) and 8-connected dinuclear molecular building blocks. X-dia-6-Ni exhibited gas (CO2, N2, CH4) and liquid (C8 hydrocarbons)-induced reversible transformations between its activated narrow-pore ß phase and γ, a large-pore phase with ca. 33% increase in unit cell volume. Single-crystal X-ray diffraction (SCXRD) studies of the as-synthesized phase α, ß, and γ revealed that structural transformations were enabled by twisting of the azo moiety and/or deformation of the MBB. Further insight into these transformations was gained from variable temperature powder XRD and in situ variable pressure powder XRD. Low-temperature N2 and CO2 sorption revealed stepped Type F-II isotherms with saturation uptakes of 422 and 401 cm3/g, respectively. X-dia-6-Ni exhibited uptake of 200 cm3/cm3 (65 atm, 298 K) and a high CH4 working capacity of 166 cm3/cm3 (5-65 bar, 298 K, 33 cycles), the third highest value yet reported for an FMOM and the highest value for an FMOM with a Type F-II isotherm.

5.
Exp Dermatol ; 33(1): e14969, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37967213

RESUMEN

Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/ß-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/ß-catenin signalling pathway and could be a potential treatment target for hair loss diseases.


Asunto(s)
Folículo Piloso , beta Catenina , Ratones , Animales , Folículo Piloso/metabolismo , beta Catenina/metabolismo , Ratones Desnudos , Biglicano/metabolismo , Ratones Endogámicos C57BL , Vía de Señalización Wnt/genética , Alopecia/metabolismo , Regeneración/fisiología , Proliferación Celular
6.
Int J Mol Sci ; 25(6)2024 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-38542377

RESUMEN

5-Fluorouracil (5-FU) stands as one of the most widely prescribed chemotherapeutics. Despite over 60 years of study, a systematic synopsis of how 5-FU binds to proteins has been lacking. Investigating the specific binding patterns of 5-FU to proteins is essential for identifying additional interacting proteins and comprehending their medical implications. In this review, an analysis of the 5-FU binding environment was conducted based on available complex structures. From the earliest complex structure in 2001 to the present, two groups of residues emerged upon 5-FU binding, classified as P- and R-type residues. These high-frequency interactive residues with 5-FU include positively charged residues Arg and Lys (P type) and ring residues Phe, Tyr, Trp, and His (R type). Due to their high occurrence, 5-FU binding modes were simplistically classified into three types, based on interactive residues (within <4 Å) with 5-FU: Type 1 (P-R type), Type 2 (P type), and Type 3 (R type). In summary, among 14 selected complex structures, 8 conform to Type 1, 2 conform to Type 2, and 4 conform to Type 3. Residues with high interaction frequencies involving the N1, N3, O4, and F5 atoms of 5-FU were also examined. Collectively, these interaction analyses offer a structural perspective on the specific binding patterns of 5-FU within protein pockets and contribute to the construction of a structural interactome delineating the associations of the anticancer drug 5-FU.


Asunto(s)
Antineoplásicos , Fluorouracilo , Fluorouracilo/metabolismo , Proteínas
7.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38892307

RESUMEN

Carnivorous pitcher plants from the genus Nepenthes are renowned for their ethnobotanical uses. This research explores the therapeutic potential of Nepenthes miranda leaf extract against nonstructural protein 9 (Nsp9) of SARS-CoV-2 and in treating human non-small cell lung carcinoma (NSCLC) cell lines. Nsp9, essential for SARS-CoV-2 RNA replication, was expressed and purified, and its interaction with ssDNA was assessed. Initial tests with myricetin and oridonin, known for targeting ssDNA-binding proteins and Nsp9, respectively, did not inhibit the ssDNA-binding activity of Nsp9. Subsequent screenings of various N. miranda extracts identified those using acetone, methanol, and ethanol as particularly effective in disrupting Nsp9's ssDNA-binding activity, as evidenced by electrophoretic mobility shift assays. Molecular docking studies highlighted stigmast-5-en-3-ol and lupenone, major components in the leaf extract of N. miranda, as potential inhibitors. The cytotoxic properties of N. miranda leaf extract were examined across NSCLC lines H1975, A549, and H838, focusing on cell survival, apoptosis, and migration. Results showed a dose-dependent cytotoxic effect in the following order: H1975 > A549 > H838 cells, indicating specificity. Enhanced anticancer effects were observed when the extract was combined with afatinib, suggesting synergistic interactions. Flow cytometry indicated that N. miranda leaf extract could induce G2 cell cycle arrest in H1975 cells, potentially inhibiting cancer cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 19 most abundant compounds in the leaf extract of N. miranda. These outcomes underscore the dual utility of N. miranda leaf extract in potentially managing SARS-CoV-2 infection through Nsp9 inhibition and offering anticancer benefits against lung carcinoma. These results significantly broaden the potential medical applications of N. miranda leaf extract, suggesting its use not only in traditional remedies but also as a prospective treatment for pulmonary diseases. Overall, our findings position the leaf extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and antiviral therapies, warranting further investigation into its molecular mechanisms and potential clinical applications.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Simulación del Acoplamiento Molecular , Extractos Vegetales , Hojas de la Planta , SARS-CoV-2 , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Hojas de la Planta/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Línea Celular Tumoral , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/antagonistas & inhibidores , Células A549 , Tratamiento Farmacológico de COVID-19 , COVID-19/virología , COVID-19/metabolismo , Apoptosis/efectos de los fármacos , Antivirales/farmacología , Antivirales/química
8.
J Am Chem Soc ; 145(39): 21483-21490, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37736678

RESUMEN

One-step adsorptive purification of ethylene (C2H4) from a ternary mixture of acetylene (C2H2), C2H4, and ethane (C2H6) by a single material is of great importance but challenging in the petrochemical industry. Herein, a chemically robust olefin-linked covalent organic framework (COF), NKCOF-62, is designed and synthesized by a melt polymerization method employing tetramethylpyrazine and terephthalaldehyde as cheap monomers. This method avoids most of the disadvantages of classical solvothermal methods, which enable the cost-effective kilogram fabrication of olefin-linked COFs in one pot. Furthermore, NKCOF-62 shows remarkably selective adsorption of C2H2 and C2H6 over C2H4 thanks to its unique pore environments and suitable pore size. Breakthrough experiments demonstrate that polymer-grade C2H4 can be directly obtained from C2H2/C2H6/C2H4 (1/1/1) ternary mixtures through a single separation process. Notably, NKCOF-62 is the first demonstration of the potential to use COFs for C2H2/C2H6/C2H4 separation, which provides a blueprint for the design and construction of robust COFs for industrial gas separations.

9.
J Am Chem Soc ; 145(11): 6507-6515, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36908113

RESUMEN

Developing strategies to enhance the structural robustness of covalent organic frameworks (COFs) is of great importance. Here, we rationally design and synthesize a class of cross-linked COFs (CCOFs), in which the two-dimensional (2D) COF layers are anchored and connected by polyethylene glycol (PEG) or alkyl chains through covalent bonds. The bottom-up fabrication of these CCOFs is achieved by the condensation of cross-linked aldehyde monomers and tritopic amino monomers. All the synthesized CCOFs possess high crystallinity and porosity, and enhanced structural robustness surpassing the typical 2D COFs, which means that they cannot be exfoliated under ultrasonication and grinding due to the cross-linking effect. Furthermore, the cross-linked patterns of PEG units are uncovered by experimental results and Monte Carlo molecular dynamics simulations. It is found that all CCOFs are dominated by vertical cross-layer (interlayer) connections (clearly observed in high-resolution transmission electron microscopy images), allowing them to form quasi-three-dimensional (quasi-3D) structures. This work bridges the gap between 2D COFs and 3D COFs and provides an efficient way to improve the interlayered stability of COFs.

10.
Small ; 19(32): e2303684, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37191288

RESUMEN

Controllable modulation of the stacking modes of 2D (two-dimensional) materials can significantly influence their properties and functionalities but remains a formidable synthetic challenge. Here, an effective strategy is proposed to control the layer stacking of imide-linked 2D covalent organic frameworks (COFs) by altering the synthetic methods. Specifically, a modulator-assisted method can afford a COF with rare ABC stacking without the need for any additives, while solvothermal synthesis leads to AA stacking. The variation of interlayer stacking significantly influences their chemical and physical properties, including morphology, porosity, and gas adsorption performance. The resultant COF with ABC stacking shows much higher C2 H2 capacity and selectivity over CO2 and C2 H4 than the COF with AA stacking, which is not demonstrated in the COF field yet. Furthermore, the outstanding practical separation ability of ABC stacking COF is confirmed by breakthrough experiments of C2 H2 /CO2 (50/50, v/v) and C2 H2 /C2 H4 (1/99, v/v), which can selectively remove C2 H2 with good recyclability. This work provides a new direction to produce COFs with controllable interlayer stacking modes.

11.
Ann Surg Oncol ; 30(5): 2942-2953, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36352297

RESUMEN

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Nomogramas , Pronóstico , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Gástricas/patología , Recurrencia Local de Neoplasia/patología
12.
Respir Res ; 24(1): 54, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36803383

RESUMEN

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.


Asunto(s)
COVID-19 , Tuberculosis Pulmonar , Tuberculosis , Humanos , Incidencia , Pandemias/prevención & control , COVID-19/epidemiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tuberculosis/epidemiología
13.
BMC Cancer ; 23(1): 1198, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057830

RESUMEN

BACKGROUND: Due to the high drug resistance of hepatocellular carcinoma (HCC), sorafenib has limited efficacy in the treatment of advanced HCC. Cancer-associated fibroblasts (CAFs) play an important regulatory role in the induction of chemoresistance. This study aimed to clarify the mechanism underlying CAF-mediated resistance to sorafenib in HCC. METHODS: Immunohistochemistry and immunofluorescence showed that the activation of CAFs was enhanced in HCC tissues. CAFs and paracancerous normal fibroblasts (NFs) were isolated from the cancer and paracancerous tissues of HCC, respectively. Cell cloning assays, ELISAs, and flow cytometry were used to detect whether CAFs induced sorafenib resistance in HCC cells via CXCL12. Western blotting and qPCR showed that CXCL12 induces sorafenib resistance in HCC cells by upregulating FOLR1. We investigated whether FOLR1 was the target molecule of CAFs regulating sorafenib resistance in HCC cells by querying gene expression data for human HCC specimens from the GEO database. RESULTS: High levels of activated CAFs were present in HCC tissues but not in paracancerous tissues. CAFs decreased the sensitivity of HCC cells to sorafenib. We found that CAFs secrete CXCL12, which upregulates FOLR1 in HCC cells to induce sorafenib resistance. CONCLUSIONS: CAFs induce sorafenib resistance in HCC cells through CXCL12/FOLR1.


Asunto(s)
Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Fibroblastos/metabolismo , Resistencia a Antineoplásicos , Proliferación Celular , Receptor 1 de Folato/metabolismo , Receptor 1 de Folato/uso terapéutico , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo
14.
Sensors (Basel) ; 23(8)2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37112304

RESUMEN

Nuts are the cornerstone of human industrial construction, especially A-grade nuts that can only be used in power plants, precision instruments, aircraft, and rockets. However, the traditional nuts inspection method is to manually operate the measuring instrument for conducting an inspection, so the quality of the A-grade nut cannot be guaranteed. In this work, a machine vision-based inspection system was proposed, which performs a real-time geometric inspection of the nuts before and after tapping on the production line. In order to automatically screen out A-Grade nuts on the production line, there are 7 inspections within this proposed nut inspection system. The measurements of parallel, opposite side length, straightness, radius, roundness, concentricity, and eccentricity were proposed. To shorten the overall detection time regarding nut production, the program needed to be accurate and uncomplicated. By modifying the Hough line and Hough circle, the algorithm became faster and more suitable for nut detection. The optimized Hough line and Hough circle can be used for all measures in the testing process.

15.
Sensors (Basel) ; 23(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37766059

RESUMEN

Currently, the majority of industrial metal processing involves the use of taps for cutting. However, existing tap machines require relocation to specialized inspection stations and only assess the condition of the cutting edges for defects. They do not evaluate the quality of the cutting angles and the amount of removed material. Machine vision, a key component of smart manufacturing, is commonly used for visual inspection. Taps are employed for processing various materials. Traditional tap replacement relies on the technician's accumulated empirical experience to determine the service life of the tap. Therefore, we propose the use of visual inspection of the tap's external features to determine whether replacement or regrinding is needed. We examined the bearing surface of the tap and utilized single images to identify the cutting angle, clearance angle, and cone angles. By inspecting the side of the tap, we calculated the wear of each cusp. This inspection process can facilitate the development of a tap life system, allowing for the estimation of the durability and wear of taps and nuts made of different materials. Statistical analysis can be employed to predict the lifespan of taps in production lines. Experimental error is 16 µm. Wear from tapping 60 times is equivalent to 8 s of electric grinding. We have introduced a parameter, thread removal quantity, which has not been proposed by anyone else.

16.
Molecules ; 28(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36677881

RESUMEN

Allantoinase (ALLase; EC 3.5.2.5) possesses a binuclear metal center in which two metal ions are bridged by a posttranslationally carbamylated lysine. ALLase acts as a key enzyme for the biogenesis and degradation of ureides by catalyzing the conversion of allantoin into allantoate. Biochemically, ALLase belongs to the cyclic amidohydrolase family, which also includes dihydropyrimidinase, dihydroorotase, hydantoinase (HYDase), and imidase. Previously, the crystal structure of ALLase from Escherichia coli K-12 (EcALLase-K12) was reported; however, the two active site loops crucial for substrate binding were not determined. This situation would limit further docking and protein engineering experiments. Here, we solved the crystal structure of E. coli BL21 ALLase (EcALLase-BL21) at a resolution of 2.07 Å (PDB ID 8HFD) to obtain more information for structural analyses. The structure has a classic TIM barrel fold. As compared with the previous work, the two missed active site loops in EcALLase-K12 were clearly determined in our structure of EcALLase-BL21. EcALLase-BL21 shared active site similarity with HYDase, an important biocatalyst for industrial production of semisynthetic penicillin and cephalosporins. Based on this structural comparison, we discussed the functional role of the two active site loops in EcALLase-BL21 to better understand the substrate/inhibitor binding mechanism for further biotechnological and pharmaceutical applications.


Asunto(s)
Escherichia coli K12 , Escherichia coli , Escherichia coli/metabolismo , Dominio Catalítico , Amidohidrolasas/química , Catálisis , Cristalografía por Rayos X , Sitios de Unión
17.
Acta Chir Belg ; 123(6): 666-672, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36322503

RESUMEN

BACKGROUND: The reconstruction of microsurgery emphasizes the low morbidity of donor sites. The arterialized venous flaps (AVFs) are tissue flaps harvested without conventional vascular pedicles. However, reports of high necrosis rates and poor understanding of physiology hindered the application of many surgeons in clinical practice. Recently, experimental and clinical studies have demonstrated the feasibility and relative reliability of various AVF techniques. This study aims to report the clinical results of the arterialized venous free flaps in reconstructing soft tissue defects of limbs and propose methods to improve flap perfusion, extending the indications for using the flaps based on the authors' clinical experiences. METHODS: We retrospectively reviewed the records of 16 patients that underwent arterialized venous free flaps for limb wound reconstruction from January 2019 to June 2021. Following the venous network on the calf's tibial side, large venous flaps can be designed. RESULTS: Of the 16 cases, 14 (87.50%) cases (including 8 cases significantly congested with tension blisters) showed complete survival, and 2 (12.5%) cases, which had only one vein performed anastomosis of the efferent vein according to the vascularity of the recipient bed, showed partial necrosis. In all cases, no infection or other specific complications occurred in the donor areas. CONCLUSION: The rate of congestion and necrosis of arterialized venous flaps is still challenging, but it will be suitable for large soft tissue defects of limbs in the future.


Asunto(s)
Traumatismos de los Dedos , Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Traumatismos de los Dedos/cirugía , Resultado del Tratamiento , Traumatismos de los Tejidos Blandos/cirugía , Colgajos Tisulares Libres/irrigación sanguínea , Colgajos Tisulares Libres/cirugía , Extremidades/cirugía , Necrosis/cirugía
18.
Angew Chem Int Ed Engl ; 62(6): e202217240, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36478518

RESUMEN

Developing new materials for anhydrous proton conduction under high-temperature conditions is significant and challenging. Herein, we create a series of highly crystalline covalent organic frameworks (COFs) via a pore engineering approach. We simultaneously engineer the pore geometry (generating concave dodecagonal nanopores) and pore surface (installing multiple functional groups such as -C=N-, -OH, -N=N- and -CF3 ) to improve the utilization efficiency and host-guest interaction of proton carriers, hence benefiting the enhancement of anhydrous proton conduction. Upon loading with H3 PO4 , COFs can realize a proton conductivity of 2.33×10-2  S cm-1 under anhydrous conditions, among the highest values of all COF materials. These materials demonstrate good stability and maintain high proton conductivity over a wide temperature range (80-160 °C). This work paves a new way for designing COFs for anhydrous proton conduction applications, which shows great potential as high-temperature proton exchange membranes.

19.
J Am Chem Soc ; 144(38): 17351-17358, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36121772

RESUMEN

Catalytic branch-selective hydrofunctionalization of feedstock α-olefins to form enantioenriched chiral compounds is a particularly attractive yet challenging transformation in asymmetric catalysis. Herein we report an iridium-catalyzed asymmetric hydroalkenylation of α-olefins through directed C-H cleavage of enamides. This atom-economical addition process is highly branch-selective and enantioselective, delivering trisubstituted alkenes with an allylic stereocenter. DFT calculations reveal the origin of regio- and enantioselectivity.


Asunto(s)
Alquenos , Iridio , Catálisis , Estereoisomerismo
20.
J Am Chem Soc ; 144(12): 5643-5652, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35313103

RESUMEN

Developing cost-/energy-efficient separation techniques for purifying ethylene from an ethylene/ethane mixture is highly important but very challenging in the industrial process. Herein, using a bottom-up [8 + 2] construction approach, we rationally designed and synthesized three three-dimensional covalent organic frameworks (COFs) with 8-connected bcu networks, which can selectively remove ethane from an ethylene/ethane mixture with high efficiency. These COF materials, which are fabricated by the condensation reaction of a customer-designed octatopic aldehyde monomer with linear diamino linkers, possess high crystallinity, good structural robustness, and high porosity. Attributed to the well-organized micro-sized pores with a nonpolar/inert pore environment, these COFs display high ethane adsorption capacity and good selectivity over ethylene, making them among the best ethane-selective adsorbents for ethylene purification. Their excellent ethylene/ethane separation performance is validated by dynamic breakthrough experiments with high-purity ethylene (>99.99%) produced through a single adsorption process. The separation performance surpasses all reported C2H6-selective COFs and even some benchmark metal-organic frameworks. This work provides important guidance for the design of new adsorbents for value-added gas purification.

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