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1.
ACS Appl Mater Interfaces ; 16(32): 42491-42501, 2024 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-39099453

RÉSUMÉ

Two-dimensional (2D) van der Waals heterostructures that embody the electronic characteristics of each constituent material have found extensive applications. Alloy engineering further enables the modulation of the electronic properties in these structures. Consequently, we envisage the construction and modulation of composition-dependent antiambipolar transistors (AATs) using van der Waals heterostructures and alloy engineering to advance multivalued inverters. In this work, we calculate the electron structures of SnSe2(1-x)S2x alloys and determine the energy band alignment between SnSe2(1-x)S2x and 2H-MoTe2. We present a series of vertical AATs based on the SnSe2(1-x)S2x/MoTe2 type-III van der Waals heterostructure. These transistors exhibit composition-dependent antiambipolar characteristics through the van der Waals heterostructure, except for the SnSe2/MoTe2 transistor. The peak current (Ipeak) decreases from 43 nA (x = 0.25) to 0.8 nA (x = 1) at Vds = -2 V, while the peak-to-valley current ratio (PVR) increases from 4.5 (x = 0.25) to 6.7 × 103 (x = 1) with a work window ranging from 30 to 47 V. Ultimately, we successfully apply several specific SnSe2(1-x)S2x/MoTe2 devices in binary and ternary logic inverters. Our results underscore the efficacy of alloy engineering in modulating the characteristics of AATs, offering a promising strategy for the development of multivalued logic devices.

2.
ACS Appl Mater Interfaces ; 16(29): 38231-38242, 2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39001805

RÉSUMÉ

The attractive physical properties of two-dimensional (2D) semiconductors in group IVA-VIA have been fully revealed in recent years. Combining them with 2D ambipolar materials to construct van der Waals heterojunctions (vdWHs) can offer tremendous opportunities for designing multifunctional electronic and optoelectronic devices, such as logic switching circuits, half-wave rectifiers, and broad-spectrum photodetectors. Here, an optimized SnSe0.75S0.25 is grown to design a SnSe0.75S0.25/MoTe2 vdWH for logic operation and wide-spectrum photodetection. Benefiting from the excellent gate modulation under the appropriate sulfur substitution and type-II band alignment, the device exhibits reconfigurable antiambipolar and ambipolar transfer behaviors at positive and negative source-drain voltage (Vds), enabling stable XNOR logic operation. It also features a gate-modulated positive and negative rectifying behavior with rectification ratios of 265:1 and 1:196, confirming its potential as half-wave logic rectifiers. Besides, the device can respond from visible to infrared wavelength up to 1400 nm. Under 635 nm illumination, the maximum responsivity of 1.16 A/W and response time of 657/500 µs are achieved at the Vds of -2 V. Furthermore, due to the strong in-plane anisotropic structure of SnSe0.75S0.25-alloyed nanosheet and narrow bandgap of 2H-MoTe2, it shows a broadband polarization-sensitive function with impressive photocurrent anisotropic ratios of 15.6 (635 nm), 7.0 (808 nm), and 3.7 (1310 nm). The direction along the maximum photocurrent can be reconfigurable depending on the wavelengths. These results indicate that our designed alloyed SnSe0.75S0.25/MoTe2 vdWH has reconfigurable logic operation and broadband photodetection capabilities in 2D multifunctional integrated circuits.

3.
Microorganisms ; 12(6)2024 Jun 06.
Article de Anglais | MEDLINE | ID: mdl-38930543

RÉSUMÉ

Acanthamoeba, a widely distributed free-living amoeba found in various environments, is an opportunistic pathogen responsible for causing Acanthamoeba keratitis, a condition that may lead to blindness. However, identifying the pathogenicity of Acanthamoeba is challenging due to its complex life cycle, ability to adapt to different environments, variable virulence factors, and intricate interactions with the host immune system. Additionally, the development of an effective model for studying Acanthamoeba pathogenicity is limited, hindering a comprehensive understanding of the mechanisms underlying its virulence and host interactions. The aim of this study was to develop an ex vivo model for Acanthamoeba infection using porcine eyeballs and to evaluate the pathogenicity of the Acanthamoeba isolates. Based on slit lamp and biopsy analysis, the developed ex vivo model is capable of successfully infecting Acanthamoeba within 3 days. Histopathological staining revealed that clinical isolates of Acanthamoeba exhibited greater corneal stroma destruction and invasion in this model than environmental isolates. Our results highlight the importance of an ex vivo porcine eye model in elucidating the pathogenesis of Acanthamoeba infection and its potential implications for understanding and managing Acanthamoeba-related ocular diseases.

4.
ACS Appl Mater Interfaces ; 16(26): 33740-33751, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38907704

RÉSUMÉ

A two-dimensional (2D) broken-gap (type-III) p-n heterojunction has a unique charge transport mechanism because of nonoverlapping energy bands. In light of this, type-III band alignment can be used in tunneling field-effect transistors (TFETs) and Esaki diodes with tunable operation and low consumption by highlighting the advantages of tunneling mechanisms. In recent years, 2D tunneling photodiodes have gradually attracted attention for novel optoelectronic performance with a combination of strong light-matter interaction and tunable band alignment. However, an in-depth understanding of the tunneling mechanisms should be further investigated, especially for developing electronic and optoelectronic applications. Here, we report a type-III tunneling photodiode based on a 2D multilayered p-GeS/n+-SnSe2 heterostructure, which is first fabricated by the mechanical exfoliation and dry transfer method. Through the Simmons approximation, its various tunneling transport mechanisms dependent on bias and light are demonstrated as the origin of excellent bidirectional photoresponse performance. Moreover, compared to the traditional p-n photodiode, the device enables bidirectional photoresponse capability, including maximum responsivity values of 43 and 8.7 A/W at Vds = 1 and -1 V, respectively, with distinctive photoactive regions from the scanning photocurrent mapping. Noticeably, benefiting from the in-plane anisotropic structure of GeS, the device exhibits an enhanced photocurrent anisotropic ratio of 9, driven by the broader depletion region at Vds = -3 V under 635 nm irradiation. Above all, the results suggest that our designed architecture can be potentially applied to CMOS imaging sensors and polarization-sensitive photodetectors.

5.
Int J Parasitol Drugs Drug Resist ; 25: 100550, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38821038

RÉSUMÉ

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.


Sujet(s)
Acanthamoeba castellanii , Biguanides , Ouabaïne , Biguanides/pharmacologie , Acanthamoeba castellanii/effets des médicaments et des substances chimiques , Ouabaïne/pharmacologie , Kératite à Acanthamoeba/parasitologie , Kératite à Acanthamoeba/traitement médicamenteux , Antienzymes/pharmacologie , Humains , Synergie des médicaments , Adenosine triphosphatases/antagonistes et inhibiteurs , Adenosine triphosphatases/effets des médicaments et des substances chimiques , Désinfectants/pharmacologie , Sodium-Potassium-Exchanging ATPase/antagonistes et inhibiteurs
6.
J Orthop Surg (Hong Kong) ; 32(2): 10225536241257169, 2024.
Article de Anglais | MEDLINE | ID: mdl-38769768

RÉSUMÉ

Background: The purpose of this study was to investigate the effect of 3D-printed technology to repair glenoid bone defect on shoulder joint stability. Methods: The shoulder joints of 25 male cadavers were tested. The 3D-printed glenoid pad was designed and fabricated. The specimens were divided into 5 groups. Group A: no bone defect and the structure of the glenoid labrum and joint capsule was intact; Group B: Anterior inferior bone defect of the shoulder glenoid; Group C: a pad with a width of 2 mm was installed; Group D: a pad with a width of 4 mm was installed; Group E: a pad with a width of 6 mm was installed. This study measured the distance the humeral head moved forward at the time of glenohumeral dislocation and the maximum load required to dislocate the shoulder. Results: The shoulder joint stability and humerus displacement was significantly lower in groups B and C compared with group A (p < .05). Compared with group A, the stability of the shoulder joint of group D was significantly improved (p < .05). However, there was no significant difference in humerus displacement between groups D and A (p > .05). In addition, compared with group A, shoulder joint stability was significantly increased and humerus displacement was significantly decreased in group E (p < .05). Conclusion: The 3D-printed technology can be used to make the shoulder glenoid pad to perfectly restore the geometric shape of the shoulder glenoid articular surface. Moreover, the 3D-printed pad is 2 mm larger than the normal glenoid width to restore the initial stability of the shoulder joint.


Sujet(s)
Alliages , Cadavre , Impression tridimensionnelle , Articulation glénohumérale , Titane , Humains , Mâle , Articulation glénohumérale/chirurgie , Articulation glénohumérale/physiopathologie , Phénomènes biomécaniques , Instabilité articulaire/chirurgie , Instabilité articulaire/physiopathologie , Cavité glénoïde/chirurgie , Conception de prothèse
7.
J Orthop Translat ; 45: 168-177, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38549808

RÉSUMÉ

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract).

8.
ACS Nano ; 18(8): 6702-6717, 2024 Feb 27.
Article de Anglais | MEDLINE | ID: mdl-38359389

RÉSUMÉ

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.


Sujet(s)
Vaccins anticancéreux , Nanoparticules , Tumeurs , Humains , , Antigènes néoplasiques , Immunothérapie , Cellules dendritiques
9.
J Exp Clin Cancer Res ; 43(1): 56, 2024 Feb 26.
Article de Anglais | MEDLINE | ID: mdl-38403634

RÉSUMÉ

BACKGROUND: Ovarian cancer (OC) is a prevalent malignancy in the female reproductive system, and developing effective targeted therapies for this disease remains challenging. The aim of this study was to use clinically-relevant OC models to evaluate the therapeutic effectiveness of RC48, an antibody-drug conjugate (ADC) targeting HER2, either alone or in combination with the VEGFR inhibitor Cediranib Maleate (CM), for the treatment of advanced OC. METHODS: OC tumor specimens and cell lines were analyzed to determine HER2 and VEGFR expression by Western blot, immunocytochemistry and immunofluorescence. Moreover, the OC cell lines, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were treated with RC48 and/or CM and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for OC both in vitro and in vivo. Additionally, RNA-Seq was performed to investigate the critical mechanism underlying the combination therapy of RC48 and CM. RESULTS: Our results demonstrated that RC48 alone effectively targeted and inhibited the growth of HER2-positive OC tumors in both cell lines and PDX models. Furthermore, the combination of RC48 and CM synergistically induced tumor regression in human OC cell lines, as well as CDX and PDX models. Mechanistically, we observed that the combination treatment inhibited the growth of OC cells involved inducing apoptosis and suppressing cell motility. RNA-seq analysis provided further mechanistic insights and revealed that co-administration of RC48 and CM downregulated multiple cancer-related pathways, including the AKT/mTOR pathway, cell cycle, and cell proliferation. Notably, our data further confirmed that the PI3K-AKT pathway played a key role in the inhibition of proliferation triggered by combinational treatment of RC48 and CM in OC cells. CONCLUSIONS: These findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC.


Sujet(s)
Tumeurs de l'ovaire , Protéines proto-oncogènes c-akt , Humains , Femelle , Protéines proto-oncogènes c-akt/métabolisme , Phosphatidylinositol 3-kinases/métabolisme , Carcinome épithélial de l'ovaire , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/génétique , Tumeurs de l'ovaire/métabolisme , Prolifération cellulaire , Lignée cellulaire tumorale
10.
Adv Sci (Weinh) ; 11(18): e2303752, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38311573

RÉSUMÉ

Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP-derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC-markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP-outer subset. Cell lineage tracing further evidence that a small number of Ctsk-expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2-cre-mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.


Sujet(s)
Nucleus pulposus , Cellules souches , Transcriptome , Animaux , Souris , Nucleus pulposus/métabolisme , Nucleus pulposus/cytologie , Cellules souches/métabolisme , Transcriptome/génétique , Différenciation cellulaire/génétique , Dégénérescence de disque intervertébral/génétique , Dégénérescence de disque intervertébral/métabolisme , Analyse de profil d'expression de gènes/méthodes , Modèles animaux de maladie humaine
11.
BMC Musculoskelet Disord ; 25(1): 29, 2024 Jan 02.
Article de Anglais | MEDLINE | ID: mdl-38166887

RÉSUMÉ

BACKGROUND: To evaluate the outcome of shoulder arthroscopy-assisted implantation of three-dimensional (3D)-printed titanium pads for recurrent shoulder dislocation with glenoid bone defects. METHODS: From June 2019 to May 2020, the clinical efficacy of 3D printed titanium pad implantation assisted by shoulder arthroscopy, for the treatment of recurrent shoulder dislocations with shoulder glenoid defects was retrospectively analyzed. The American Shoulder and Elbow Surgeons (ASES) shoulder, Rowe, and Constant scores were recorded before surgery and at 3 months, 6 months, 1 year, and 2 years after surgery. 3D computed tomography (CT) and magnetic resonance imaging were used to evaluate the location of the glenoid pad, bone ingrowth, joint degeneration, and osteochondral damage. RESULTS: The mean age of the 12 patients was 21.4 (19-24) years and the mean follow-up time was 27.6 (24-35) months. The Visual Analog Scale score significantly improved from 5.67 ± 1.98 preoperatively to 0.83 ± 0.58 postoperatively (p = 0.012). The postoperative ASES score was significantly increased to 87.91 ± 3.47 compared with preoperative ASES score (46.79 ± 6.45) (p < 0.01). Rowe and Constant scores also improved from 22.5 ± 12.34 and 56.58 ± 7.59 preoperatively to 90.83 ± 4.69 and 90.17 ± 1.89 at 2 years postoperatively, respectively. CT performed 2 years after surgery showed that the pad perfectly replenished the bone-defective part of the shoulder glenoid and restored the articular surface curvature of the shoulder glenoid in the anterior-posterior direction, and the bone around the central riser of the pad was tightly united. Magnetic resonance imaging 2 years after surgery showed that the humeral head osteochondral bone was intact, and there was no obvious osteochondral damage. CONCLUSIONS: 3D printed titanium pads are a reliable, safe, and effective surgical procedure for treating recurrent shoulder dislocations with glenoid bone defects.


Sujet(s)
Instabilité articulaire , Luxation de l'épaule , Articulation glénohumérale , Humains , Jeune adulte , Adulte , Luxation de l'épaule/imagerie diagnostique , Luxation de l'épaule/chirurgie , Articulation glénohumérale/imagerie diagnostique , Articulation glénohumérale/chirurgie , Titane , Études de suivi , Études rétrospectives , Instabilité articulaire/chirurgie , Arthroscopie/méthodes , Impression tridimensionnelle , Récidive
13.
Opt Lett ; 48(23): 6108-6111, 2023 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-38039203

RÉSUMÉ

Polarization-sensitive photodetectors in the ultraviolet (UV) region have been favored for their great meaning in the field of military and civilian. UV photodetectors based on GaN have aroused much attention due to high photocurrent and high sensitivity. However, the dependence on external power sources and the limited sensitivity to polarized UV light significantly impede the practical application of these photodetectors in UV-polarized photodetection. Herein, a polarization-sensitive UV photodetector based on ReSe2/GaN mixed-dimensional van der Waals (vdWs) heterojunction is proposed. Owing to the high-quality junction and type-II band alignment, the responsivity and specific detectivity reach values of 870 mA/W and 6.8 × 1011 Jones, under 325 nm illumination, respectively. Furthermore, thanks to the strong in-plane anisotropy of ReSe2, the device is highly sensitive to polarized UV light with a photocurrent anisotropic ratio up to 6.67. The findings are expected to bring new opportunities for the development of highly sensitive, high-speed and energy-efficient polarization-sensitive photodetectors.

14.
Sci Rep ; 13(1): 18717, 2023 10 31.
Article de Anglais | MEDLINE | ID: mdl-37907647

RÉSUMÉ

Pueraria lobata is a typical medicinal and edible plant with great market value and demand, thus exploring the relationship between soil environmental factors and the yield and quality of Pueraria lobata is of great significance for its high-value cultivation. In this study, using the Guige 1 variety (Pueraria montana var. Thomsonii) selected by our research group as the material to compare the effects of five soil types, endophytes in three parts of Pueraria lobata and two fertilizers on its yield and quality. The results showed that the comprehensive evaluation effect of five soil types on the yield and quality of Guige 1 was as follow: red-yellow mixed soil (RYMS) > black loam soil (BLS) > sandy loam soil (SLS) > sandy loam soil waterlogging (SLSW) > yellow soil compaction soil (YSCS); the descending order of endophyte types and quantities is in BLS > RYMS > SLS > YSC > SLSW; applying General Compound Fertilizers (GCF) in RYMS is more suitable for the rapid expansion of Guige 1 than Organic-Slow-Release-Fertilizers (OSRF). The high potassium content in RYMS and high effective phosphorus content in BLS are positively correlated with the content of starch and isoflavone in Pueraria lobata. The conclusion is that the high potassium and available phosphorus content in RYMS and BLS, as well as the rich types and quantities of endophytic bacteria, are positively correlated with the yield and quality of Pueraria lobata. The research results have important guiding significance for the high-value cultivation of Pueraria lobata.


Sujet(s)
Isoflavones , Pueraria , Sol , Engrais , Phosphore , Potassium , Racines de plante
15.
J Am Chem Soc ; 145(51): 28085-28095, 2023 Dec 27.
Article de Anglais | MEDLINE | ID: mdl-38032206

RÉSUMÉ

The creation of full stereoisomers of an organic compound comprising multiple contiguous stereocenters with simultaneous control over both relative and absolute configurations remains a significant challenge in synthetic chemistry. Using a cooperative catalysis strategy, we established an N-heterocyclic carbene/nickel-catalyzed enantio- and diastereodivergent propargylation reaction to access 3,3'-disubstituted oxindoles, enabling the incorporation of internal alkyne functionality and the introduction of a single quaternary or vicinal quaternary/tertiary stereogenic center. By selecting the appropriate combination of catalyst chirality, all four potential stereoisomers of α-quaternary propargylated oxindoles were synthesized in a predictable and precise way with remarkable yields, diastereoselectivities, and enantioselectivities from identical starting materials. The synthetic utility of this method was demonstrated in the concise asymmetric total synthesis of (-)-debromoflustramine B and (-)-C(ß-Me)-debromoflustramine B.

16.
Nat Commun ; 14(1): 6749, 2023 Oct 24.
Article de Anglais | MEDLINE | ID: mdl-37875470

RÉSUMÉ

Quaternary amino acids are one of the essential building blocks and precursors of medicinally important compounds. Various synthetic strategies towards their synthesis have been reported. On the other hand, developing core-structure-oriented cross-dehydrogenative coupling (CDC) reactions, is a largely unsolved problem. Herein, we describe a copper-catalyzed regiodivergent electrochemical CDC reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives for the efficient assembly of complex scaffolds with excellent stereocontrol. The electrochemical anodic oxidation process with slow releasing of quinones serves as an internal syringe pump and provides high levels of reaction efficiency and enantiomeric control. The utility of this strategy is highlighted through the synthetic utility in the asymmetric total synthesis of (-)-fumimycin.

17.
Front Oncol ; 13: 1103357, 2023.
Article de Anglais | MEDLINE | ID: mdl-37564940

RÉSUMÉ

Objective: To investigate the effect of primary debulking surgery (PDS), NACT followed by interval debulking surgery (NACT-IDS), and chemotherapy alone on the prognosis of FIGO stage IV epithelial ovarian cancer (EOC) with different metastatic patterns. Methods: We retrospectively analyzed 133 cases of FIGO stage IV EOC with pleural effusion (stage IVA), parenchymal metastases (stage IVB), or extra-abdominal lymph node metastases (stage IVB) at our Hospital between January 2014 and July 2021. Results: Among 133 cases with stage IV disease, 16.5% (n=22) presented with pleural effusion, 46.6% (n=62) with parenchymal metastases, and 36.9% (n=49) with extra-abdominal lymph node metastases. Regardless of the metastatic patterns, the 90.2% (n=120) of cases who underwent PDS/NACT-IDS exhibited a significantly superior overall survival (OS) compared to the 9.8% cases (n=13) who received chemotherapy alone (32 vs 17 months, p=0.000). The cohort was further stratified into 58 cases (48.3%) with R0, 41 cases (34.2%) with R1, and 21 cases (17.5%) with R2. The median OS of cases with R0 was significantly better than that of cases with R1/R2 (74 vs 27 months, p=0.000). There was no significant difference in median OS between PDS and NACT-IDS (43 vs 31 months, p=0.676), as well as between FIGO IVA and IVB (35 vs 31 months, p=0.582). Additionally, the metastatic patterns and the number of neoadjuvant chemotherapy cycles (≤4 or >4) did not demonstrate any prognostic significance for median OS (p=0.820 and 33 vs 26 months, p=0.280, respectively). Conclusion: Regardless of FIGO IVA and IVB stages or metastatic patterns, patients diagnosed with stage IV EOC may benefit from cytoreductive surgery with abdominal R0, compared with chemotherapy alone.

18.
PLoS Negl Trop Dis ; 17(8): e0011541, 2023 08.
Article de Anglais | MEDLINE | ID: mdl-37566587

RÉSUMÉ

BACKGROUND: Acanthamoeba and Klebsiella pneumoniae are both environmental commensals. Recently, clinical harm caused by hypermucoviscous K. pneumoniae has been observed. However, the interaction between these microbes and the origin of hypermucoviscous K. pneumoniae have not been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the bacterial capsule is enlarged when co-cultured with Acanthamoeba using India ink staining, and this effect depends on the number of parasites present. This interaction results in an enhancement of capsular polysaccharide production in the subsequent generations of K. pneumoniae, even without co-culturing with Acanthamoeba. The hypermucoviscosity of the capsule was examined using the sedimentation assay and string test. We also screened other K. pneumoniae serotypes, including K1, K2, K5, and K20, for interaction with Acanthamoeba using India ink staining, and found the same interaction effect. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the interaction between Acanthamoeba and K. pneumoniae could lead to harmful consequences in public health and nosocomial disease control, particularly hypermucoviscous K. pneumoniae infections.


Sujet(s)
Acanthamoeba , Infections à Klebsiella , Humains , Klebsiella pneumoniae , Infections à Klebsiella/microbiologie , Sérogroupe
19.
J Oleo Sci ; 72(9): 869-879, 2023.
Article de Anglais | MEDLINE | ID: mdl-37648464

RÉSUMÉ

The essential oil, extracted from the Hmong medicine Blumea balsamifera (L.) DC. (BBO), is a purely natural wound repair agent. Its application has, however, been restricted due to its low solubility and high volatility properties. In this study, we have developed a nanoemulsion formulation to improve the characteristics of BBO. The particle size of the nanoemulsion was normally distributed, and 71% of its range was concentrated between 10-100 nm, with an average particle size of 62.8 nm and an encapsulation rate of 98%. After 7 days of application, the wound healing rate of the BBO nanoemulsion (BBO-NE) group was 1.5 times higher than that of the normal BBO group. Along with histological observations, nanoemulsion formulation has been demonstrated to significantly improve the efficacy of BBO for wound repair. In addition, inflammation-related TLR4, CD14 and IRAK-1 gene transcript levels were significantly reduced after the administration of BBO-NE compared to the BBO group, with downregulation of 47.8%, 35.7% and 57.8%, respectively, while the secretion of pro-inflammatory factors IL-6 and TNF-α was also significantly reduced by 83.8% and 32.7%, respectively, in the nanoformulation administration (BBO-NE) group compared to the BBO group. In contrast, the anti-inflammatory factor IL-10 was significantly increased by 4.2-fold. It was further found that the drug penetration per unit area increased significantly 6.30% to 19.5% at different time points after the application of the BBO-NE compared to the BBO. In conclusion, nano-formulation enhanced the drug penetration of the BBO, reduced inflammatory factors, increased the level of anti-inflammatory factors, and promoted collagen deposition, thereby accelerating wound repair.


Sujet(s)
Asteraceae , Huile essentielle , Huile essentielle/pharmacologie , Facteur de nécrose tumorale alpha , Cicatrisation de plaie , Animaux
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