Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that ...enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.
A highly enantioselective free carbene insertion into the N−H bond of amines has been achieved. Newly designed high‐pKa Brønsted acid catalysts, chiral spiro phosphamides, were found to be key and promote the proton transfer of the ylide intermediates and control the enantioselectivity of the reaction. The reaction provides a new approach to amino acid derivatives.
•TAMs are involved in tumor progression via multiple mechanisms.•TAMs serve as angiogenesis promoting cells in cancer.•TAMs play vital roles in tumor metastasis.•TAMs are the promising candidate in ...cancer therapy.
Tumor associated macrophages (TAMs) are the most frequent immune cells within tumor microenvironment (TME). There is growing evidence that TAMs are involved in tumor progression via multiple mechanisms. TAMs create an immunosuppressive TME by producing growth factors, chemokines, and cytokines which modulate recruitment of immune cells and inhibit anti-tumor responses. They also serve as angiogenesis promoting cells by production of pro-angiogenic factors and matrix metalloproteinases (MMPs) and vascular constructing which guarantee supplying oxygen and nutrients to solid tumor cells. Furthermore, TAMs play important functions in tumor metastasis through contributing to invasion, extravasation, survival, intravasation, and colonization of tumor cells. In this review, we summarized macrophage classification, TAMs polarization, and mechanisms underlying TAM-promoting angiogenesis and metastasis.
We have developed a one-step method to synthesize carbon quantum dots (CQDPAs) from biogenic polyamines (PAs) as an antibacterial agent for topical treatment of bacterial keratitis (BK). CQDs ...synthesized by direct pyrolysis of spermidine (Spd) powder through a simple dry heating treatment exhibit a solubility and yield much higher than those from putrescine and spermine. We demonstrate that CQDs obtained from Spds (CQDSpds) possess effective antibacterial activities against non-multidrug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica serovar Enteritidis bacteria and also against the multidrug-resistant bacteria, methicillin-resistant S. aureus. The minimal inhibitory concentration (MIC) of CQDSpds is ∼2500-fold lower than that of spermidine alone, demonstrating their strong antibacterial capabilities. Investigation of the possible mechanisms behind the antibacterial activities of the as-synthesized CQDSpds indicates that the super-cationic CQDSpds with small size (diameter ca. 6 nm) and highly positive charge (ζ-potential ca. +45 mV) cause severe disruption of the bacterial membrane. In vitro cytotoxicity, hemolysis, hemagglutination, genotoxicity, and oxidative stress and in vivo morphologic and physiologic cornea change evaluations show the good biocompatibility of CQDSpds. Furthermore, topical ocular administration of CQDSpds can induce the opening of the tight junction of corneal epithelial cells, thereby leading to great antibacterial treatment of S. aureus-induced BK in rabbits. Our results suggest that CQDSpds are a promising antibacterial candidate for clinical applications in treating eye-related bacterial infections and even persistent bacteria-induced infections.
This study reports a two‐step method to synthesize spermidine‐capped fluorescent carbon quantum dots (Spd–CQDs) and their potential application as an antibacterial agent. Fluorescent carbon quantum ...dots (CQDs) are synthesized by pyrolysis of ammonium citrate in the solid state and then modified with spermidine by a simple heating treatment without a coupling agent. Spermidine, a naturally occurring polyamine, binds with DNA, lipids, and proteins involved in many important processes within organisms such as DNA stability, and cell growth, proliferation, and death. The antimicrobial activity of the as‐synthesized Spd–CQDs (size ≈4.6 nm) has been tested against non‐multidrug‐resistant E. coli, S. aureus, B. subtilis, and P. aeruginosa bacteria and also multidrug‐resistant bacteria, methicillin‐resistant S. aureus (MRSA). The minimal inhibitory concentration value of Spd–CQDs is much lower (>25 000‐fold) than that of spermidine, indicating their promising antibacterial characteristics. The mechanism of antibacterial activity is investigated, and the results indicate that Spd–CQDs cause significant damage to the bacterial membrane. In vitro cytotoxicity and hemolysis analyses reveal the high biocompatibility of Spd–CQDs. To demonstrate its practical application, in vitro MRSA‐infected wound healing studies in rats have been conducted, which show faster healing, better epithelialization, and formation of collagen fibers when Spd–CQDs are used as a dressing material.
Spermidine, a biogenic polyamine, when self‐assembled on carbon quantum dots (CQDs), exhibits >25 000‐fold improvement in its antimicrobial activity against multidrug resistant bacteria. Antibacterial wound‐healing assays reveal that the spermidine‐modified CQDs are an effective dressing nanomaterial for treatment of bacterial infections.
Objectives
Non‐syndromic cleft lip with or without palate is one of the most common birth malformations. TP63 and GREM1 were recently reported to be associated with NSCL/P. However, there were few ...studies focused on their associations in non‐syndromic cleft lip only (NSCLO).
Design
Initial screening and replication in large cohorts were used to locate the susceptible SNPs of TP63 and GREM1. Firstly, variations were screened among 192 NSCLO cases by the Sanger sequencing. Then, we selected five associated SNPs in initial screening phase and replicated among 1,006 NSCLO cases and 1,823 normal controls.
Results
Initial chi‐square test showed that rs7653848, rs7624324, rs6790167, and rs1345186 in TP63 and rs2280738 in GREM1 achieved statistical significance (p < .05); the subsequent replication analysis showed that rs1345186 was specifically significant in right‐side cleft lip (RCL; p = .017, OR = 1.33, and 95% CI: 1.05–1.69).
Conclusion
This study firstly used the subphenotype of cleft lip samples to verify the association between TP63 and GREM1, which indicated that TP63 is a promising susceptible gene for RCL in Chinese population. And further confirmed the different etiology in the right‐sided cleft lip, left‐sided cleft lip, and bilateral cleft lip of NSCLO. This will give new reference for the future research and genetic counseling.
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•One-step pyrolysis of spermine and dopamine to prepare the antibacterial carbon quantum dots (CQDs).•The CQDs exhibit much strong antibacterial activity (>100-fold) relative to ...dopamine or spermine alone.•The CQDs possess superior adhesion to the contact lenses.•Contact lens coated with CQDs effectively alleviate S. aureus-induced bacterial keratitis.
We demonstrate the synthesis of antibacterial carbon quantum dots (CQDs) through a one-step pyrolysis of biogenic polyamine (PA) and dopamine (DA) mixture. SPM/DA-CQDs synthesized from DA combined with spermine (SPM) exhibit effective antibacterial activity and high adhesion properties on glass and surfaces of polymeric contact lens material. The antimicrobial activity of SPM/DA-CQDs is primarily due to their ability to disrupt the bacterial membrane, and they possess wide spectrum antimicrobial activity against Gram-negative bacteria (Escherichia coli, Salmonella enterica serovar Enteritidis, and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and its multidrug-resistant strain, methicillin-resistant S. aureus). The minimal inhibitory concentration (MIC) of SPM/DA-CQDs against the tested bacteria was >17-fold and >7-fold lower than those of CQDs prepared solely from spermine and dopamine, respectively. The great biocompatibility of our SPM/DA-CQDs is revealed from the in vitro cytotoxicity and hemolysis assays and in vivo evaluation of morphological and physiological changes of rabbit corneas. We further prepared SPM/DA-CQDs-coated coverslips and contact lenses, which display excellent stability and antibiofilm properties. Moreover, in vivo tests show that SPM/DA-CQDs suppress bacterial keratitis (BK) formation in a corneal-injured rabbit model. Our results indicate that SPM/DA-CQDs have great potential as a coating material for inhibition of biofilm formation on contact lenses, and broadly to protect medical devices from contamination.
How the plasma membrane senses external heat-stress signals to communicate with chloroplasts to orchestrate thermotolerance remains elusive. We identified a quantitative trait locus,
Thermo-tolerance ...3
(
TT3
), consisting of two genes,
TT3.1
and
TT3.2
, that interact together to enhance rice thermotolerance and reduce grain-yield losses caused by heat stress. Upon heat stress, plasma membrane–localized E3 ligase TT3.1 translocates to the endosomes, on which TT3.1 ubiquitinates chloroplast precursor protein TT3.2 for vacuolar degradation, implying that TT3.1 might serve as a potential thermosensor. Lesser accumulated, mature TT3.2 proteins in chloroplasts are essential for protecting thylakoids from heat stress. Our findings not only reveal a
TT3.1-TT3.2
genetic module at one locus that transduces heat signals from plasma membrane to chloroplasts but also provide the strategy for breeding highly thermotolerant crops.
Heat tolerance in rice
Too much heat can damage a plant’s chloroplasts, driving yield down when temperatures exceed a crop’s normal tolerance. Zhang
et al
. identified a locus with two genes that together enhance rice thermotolerance. The ubiquitin ligase activity of Thermo-tolerance 3.1 (TT3.1) drove degradation of TT3.2, a chloroplast precursor protein that can trigger chloroplast damage in the context of heat stress. Together, these protein products respond to heat and control the damage. —PJH
A tag team of protein degradation protects rice plants from excess heat.
Oxaliplatin (OXA) is a third-generation platinum compound with clinical activity in multiple solid tumors. Due to the repetition of chemotherapy cycle, OXA-induced chronic neuropathy presenting as ...paresthesia and pain. This study explored the neuropathy of chemotherapy pain and investigated the analgesic effect of 2-bromopalmitate (2-BP) on the pain behavior of OXA-induced rats. The chemotherapy pain rat model was established by the five consecutive administration of OXA (intraperitoneal, 4 mg/kg). After the establishment of OXA-induced rats, the pain behavior test, inflammatory signal analysis and mitochondrial function measurement were conducted. OXA-induced rats exhibited mechanical allodynia and spinal inflammatory infiltration. Our fluorescence and western blot analysis revealed spinal astrocytes were activated in OXA rats with up-regulation of astrocytic markers. In addition, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome mediated inflammatory signal cascade was also activated. Inflammation was triggered by dysfunctional mitochondria which represented by increase in cyclooxygenase-2 (COX-2) level and manganese superoxide dismutase (Mn-SOD) activity. Intrathecally injection of 2-BP significantly attenuated dynamin-related protein 1 (Drp1) mediated mitochondrial fission, recovered mitochondrial function, suppressed NLRP3 inflammasome cascade, and consequently decreased mechanical pain sensitivity. For cell research, 2-BP treatment significantly reversed tumor necrosis factor-α (TNF-α) induced mitochondria membrane potential deficiency and high reactive oxygen species (ROS) level. These findings indicate 2-BP decreases spinal inflammation and relieves OXA-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a mechanosensitive ion channel protein that is evolutionarily conserved and multifunctional. It plays an important role as an oncogenic ...mediator in several malignant tumors. It mediates the proliferation, migration, and invasion of a variety of cancer cells through various mechanisms. Multiple studies have shown that the expression of Piezo1 is related to the clinical characteristics of senescence and cancer patients, making Piezo1 useful as a new biomarker for the diagnosis and prognosis of a variety of human cancers. Manipulating the expression or function of Piezo1 is a potential therapeutic strategy for different diseases. Piezo1 may be a promising tumor biomarker and therapeutic target. Here we review the biological function, mechanism of action, and potential clinical significance of Piezo1 in oncogenesis and progression.
•This paper reviews the recent literature on piezo1.•According to the classification of disease and mechanism, the role of piezo1 on cancer field was summarized.•It is concluded that piezo1 is a biomarker of human cancer and may become a potential target for cancer diagnosis and treatment.•This review is valuable to all who are engaged in this field.
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