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1.
Opt Lett ; 46(19): 4722-4725, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598183

RESUMO

We investigate the modal properties of a beam carrying orbital angular momentum (OAM) generated by a circular array (ring) of multiple micro-ring emitters (rings) analytically and via simulation. In such a "ring-of-rings" structure, N emitters generate N optical vortex beams with the same OAM-order l0 at the same wavelength. The output beam is a coherent combination of the N vortex beams located at different azimuthal positions, having the same radial displacement. We derive an analytical expression for the output optical field and calculate the OAM-order power spectrum of the generated beam. The analytical expression and simulation results show that (1) the OAM spectrum of the output beam composes equidistant OAM spectral components, symmetrically surrounding l0 with a spacing equal to N; (2) the envelope of the OAM spectrum broadens with an increased radius of the circular array or the value of l0; and (3) the OAM components of the generated beam could be tuned either by changing the value of l0, corresponding to different spectrum envelopes, or by adding different linear phase delays to the micro-ring emitters, which does not affect the envelope of the OAM spectrum.

2.
Opt Lett ; 46(19): 4765-4768, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598194

RESUMO

We experimentally generate an orbital-angular-momentum (OAM) beam with a tunable mode order over a range of wavelengths utilizing an integrated broadband pixel-array OAM emitter. The emitter is composed of a 3-to-4 coupler, four phase controllers, and a mode convertor. An optical input is split into four waveguides by the coupler. Subsequently, the four waveguide fields are coherently combined and transformed into a free-space OAM beam by the mode convertor. By tuning the phase delay Δφ between the four waveguides using the integrated phase controllers, the OAM order of the generated beam could be changed. Our results show that (a) a single OAM beam with a tunable OAM order (ℓ=-1 or ℓ=+1) is generated with the intermodal power coupling of <-11dB, and (b) in a wavelength range of 6.4 nm, a free-space link of a single 50 Gbaud quadrature-phase-shift-keying (QPSK) channel carried by the tunable OAM beam is achieved with a bit error rate below the forward-error-correction threshold. As proof of concept, a 400 Gbit/s OAM-multiplexed and WDM QPSK link is demonstrated with a ∼1-dB OSNR penalty compared with a single-beam link.

3.
J Pharm Sci ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34547305

RESUMO

Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (ZEGFR) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR+ A431 tumor cells in vitro and in vivo. The LS-DDP coupled with ZEGFR (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro, AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 µg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 µg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of ZEGFR. In vivo, the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with ZEGFR enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR+ tumors.

4.
Nat Commun ; 12(1): 5522, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535671

RESUMO

Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N6-methyladenosine (m6A) methylation) is unclear. Here we report decreased expression of the m6A "writer" METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is m6A modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity renders NK cells hyporesponsive to IL-15, which is associated with suppressed activation of the AKT and MAPK signaling pathway in METTL3-deficient NK cells. These findings show that m6A methylation safeguards the homeostasis and tumor immunosurveillance function of NK cells.


Assuntos
Adenosina/análogos & derivados , Células Matadoras Naturais/imunologia , Metiltransferases/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , RNA/metabolismo , Adenosina/metabolismo , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Deleção de Genes , Homeostase , Interleucina-15/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Metilação , Metiltransferases/deficiência , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Microambiente Tumoral
5.
Hepatology ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510508

RESUMO

BACKGROUD AND AIMS: Liver type 1 innate lymphoid cells (ILC1s), also known as liver-resident natural killer (NK) cells, comprise a high proportion of total hepatic ILCs. However, factors regulating their maintenance and function remain unclear. APPROACH AND RESULTS: In this study, we found high expression of RORα in liver-resident NK (LrNK) cells/ILC1s. Mice with conditional ablation of Rora in LrNK cells/ILC1s and conventional NK (cNK) cells had decreased LrNK cells/ILC1s but normal numbers of cNK cells. RORα-deficient LrNK cells/ILC1s displayed increased apoptosis and significantly altered transcriptional profile. Using a murine model of colorectal cancer liver metastasis, we found that RORα conditional deficiency resulted in more aggressive liver tumor progression and impaired effector molecule expression in LrNK cells/ILC1s. Consequently, treatment with the RORα agonist efficiently limited liver metastases and promoted effector molecule expression of LrNK cells/ILC1s. CONCLUSION: Together, our study unveils a previously undefined role of RORα in LrNK cell/ILC1 maintenance and function, providing insights into the harnessing of LrNK cell/ILC1 activity in the treatment of liver cancer.

6.
Cell Death Dis ; 12(9): 799, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404767

RESUMO

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.

7.
Stem Cell Res ; 56: 102514, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34464855

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease caused by environmental and genetic factors. The identified PD genes include SNCA, LRRK2, Parkin, DJ-1, PINK1, and ATP13A2. Mutations in the glucocerebrosidase (GBA) gene were reported to be associated with PD in different ethnic populations. Here we generated a novel induced pluripotent stem cell (iPSC) line LCPHi001-A from a PD patient carrying RecNciI mutation (c.1448 T > C, c.1483G > C, and c.1497G > C) in GBA by non-integrative episomal plasmids. The LCPHi001-A line expressed pluripotency markers, displayed differentiation capacity to three germ layers in vivo, and had the normal karyotype.

8.
Nat Commun ; 12(1): 4976, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404790

RESUMO

To construct a superior microbial cell factory for chemical synthesis, a major challenge is to fully exploit cellular potential by identifying and engineering beneficial gene targets in sophisticated metabolic networks. Here, we take advantage of CRISPR interference (CRISPRi) and omics analyses to systematically identify beneficial genes that can be engineered to promote free fatty acids (FFAs) production in Escherichia coli. CRISPRi-mediated genetic perturbation enables the identification of 30 beneficial genes from 108 targets related to FFA metabolism. Then, omics analyses of the FFAs-overproducing strains and a control strain enable the identification of another 26 beneficial genes that are seemingly irrelevant to FFA metabolism. Combinatorial perturbation of four beneficial genes involving cellular stress responses results in a recombinant strain ihfAL--aidB+-ryfAM--gadAH-, producing 30.0 g L-1 FFAs in fed-batch fermentation, the maximum titer in E. coli reported to date. Our findings are of help in rewiring cellular metabolism and interwoven intracellular processes to facilitate high-titer production of biochemicals.


Assuntos
Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Ácidos Graxos não Esterificados/biossíntese , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ácidos Graxos/metabolismo , Fermentação , Regulação Bacteriana da Expressão Gênica , Engenharia Metabólica , Redes e Vias Metabólicas/genética , Transcriptoma
9.
Cell Rep ; 36(8): 109600, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433057

RESUMO

Malaria infection by Plasmodium falciparum continues to pose a global threat to the human population. P. falciparum expresses variable erythrocyte surface antigens such as RIFINs. Public antibodies with LAIR1 insertion have been identified from malarial patients against a subset of RIFINs. In this study, we solve a LAIR1-binding RIFIN structure: the complex structures of two RIFINs bound to mutated or wild-type LAIR1 in two distinct patterns. Notably, the two RIFINs engage similar binding sites on LAIR1 with different angles, and the RIFIN-binding sites overlap with the collagen-binding site. Surprisingly, RIFINs use completely different binding sites to bind to LAIR1 or LILRB1, indicating the kaleidoscopic change of RIFINs. We then verify that RIFIN could induce LAIR1-mediated cell signaling, and LAIR1-containing antibodies could block the pathway. The findings of this study provide structural insights into the mechanism of the immune escape of P. falciparum and the endless arms race between parasite and host.

11.
Sheng Li Xue Bao ; 73(4): 551-558, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405211

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are major health problems worldwide, whose incidence are closely related with each other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels were measured by ELISA to confirm the establishment of an HHcy model. Meantime, mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results showed that n-3 PUFA significantly improved hepatic lipid deposition induced by HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition of hepatic Cd36 expression was associated with the inactivation of aryl hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry revealed that hepatic content of lipoxin A5 (LXA5) was significantly increased in HMD+n-3 PUFA-fed mice compared with that in HMD-fed mice. In primary cultured hepatocytes, LXA5 treatment markedly reversed homocysteine-evoked Cd36 upregulation and Ahr activation, which resulted in reduced lipid accumulation. In conclusion, we demonstrate that n-3 PUFA inactivates HHcy-induced Ahr-Cd36 pathway by increasing hepatic LXA5 content, which alleviates hepatic steatosis. Thus, our results may provide a potential strategy for treatment of NAFLD.


Assuntos
Ácidos Graxos Ômega-3 , Fígado Gorduroso , Hiper-Homocisteinemia , Animais , Fígado Gorduroso/tratamento farmacológico , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Artigo em Inglês | MEDLINE | ID: mdl-34286432

RESUMO

Four subsurface flow constructed wetlands (SFCWs) filled with different substrates including ceramsite, ceramsite+pyrite, ceramsite+ferrous sulfide, and ceramsite+pyrite+ferrous sulfide (labeled as SFCW-S1, SFCW-S2, SFCW-S3, and SFCW-S4) were constructed, and the removal of nitrogen and phosphorus by these SFCWs coupled with intermittent aeration in the front section was discussed. The key findings from different substrate analyses, including nitrification and denitrification rate, enzyme activity, microbial community structure, and the X-ray diffraction, revealed the nitrogen and phosphorus removal mechanism. The results showed that the nitrogen and phosphorus removal efficiency for SFCW-S1 always remained the lowest, and the phosphorus removal efficiency for SFCW-S4 was recorded as the highest one. However, after controlling the dissolved oxygen by intermittent aeration in the front section of SFCWs, the nitrogen and phosphorus removal efficiencies of SFCWs-S2 and S4 became higher than those of SFCW-S1, and SFCW-S3. It was noticed that the pollutants were removed mainly in the front section of the SFCWs. Both precipitation and adsorption on the substrate were the main mechanisms for phosphorus removal. A minute difference of nitrification rate and ammonia monooxygenase activity was observed in the SFCWs' aeration zone. The denitrification rates, nitrate reductase, nitrite reductase, and electron transport system activity for SFCW-S2 and SFCW-S4 were higher than those detected for SFCW-S1 and SFCW-S3 in the non-aerated zone. Proteobacteria was the largest phyla found in the SFCWs. Moreover, Thiobacillus occupied a large proportion found in SFCW-S2, and SFCW-S4, and it played a crucial role in pyrite-driven autotrophic denitrification.

13.
Arch Microbiol ; 203(8): 4941-4950, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34255124

RESUMO

Environmental factors can alter exopolysaccharide biosynthesis in lactic acid bacteria (LAB). To further clarify this potential relationship, the mRNA expression of genes involved in exopolysaccharide synthesis such as glmU, pgmB1, cps4E, cps4F, cps4J, and cps4H in Lactiplantibacillus plantarum VAL6 under different conditions including temperature, pH, sodium chloride (NaCl), and carbon dioxide (CO2) intensification culture was studied. The transcriptomic data revealed that the exposure of L. plantarum VAL6 at pH 3 increased the expression level of cps4H but decreased the expression levels of pgmB1 and cps4E. Under pH 8, cps4F and cps4E were significantly upregulated, whereas pgmB1 was downregulated. Similarly, the expression levels of cps4F, cps4E, and cps4J increased sharply under stresses at 42 or 47 °C. In the case of NaCl stress, glmU, pgmB1, cps4J, and cps4H were downregulated in exposure to NaCl at 7 and 10% concentrations while cps4E and cps4F were upregulated at 1 h of 10%-NaCl treatment and at 5 h of 4%-NaCl treatment. Remarkably, CO2 intensification culture stimulated the expression of all tested genes. In addition, simultaneous changes in expression of cps4E and cps4F under environmental challenges may elicit the possibility of an association between the two genes. These findings indicated that the expression level of eps genes is responsible for changes in the yield and monosaccharide composition of exopolysaccharides under environmental stresses.

14.
Nano Lett ; 21(14): 5907-5913, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34251831

RESUMO

A time-dependent change in the refractive index of a material leads to a change in the frequency of an optical beam passing through that medium. Here, we experimentally demonstrate that this effect-known as adiabatic frequency conversion (AFC)-can be significantly enhanced by a nonlinear epsilon-near-zero-based (ENZ-based) plasmonic metasurface. Specifically, by using a 63-nm-thick metasurface, we demonstrate a large, tunable, and broadband frequency shift of up to ∼11.2 THz with a pump intensity of 4 GW/cm2. Our results represent a decrease of ∼10 times in device thickness and 120 times in pump peak intensity compared with the cases of bare, thicker ENZ materials for the similar amount of frequency shift. Our findings might potentially provide insights for designing efficient time-varying metasurfaces for the manipulation of ultrafast pulses.

15.
Nano Lett ; 21(15): 6471-6479, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34292757

RESUMO

Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. However, there are a few strategies that can simultaneously regulate both inflammatory and metabolic functions to achieve safe and potent antitumor activation of TAMs. Herein, we demonstrate that an iron-based metal organic framework nanoparticle and a ferroptosis-inducing agent synergistically induce mitochondrial alternation in TAMs, resulting in a radical metabolic switch from mitochondrial oxidative phosphorylation to glycolysis, which is resistant to anti-inflammatory stimuli challenge. The ferroptosis stress strengthened by the nanoformulation also drives multiple pro-inflammatory signaling pathways, enabling macrophage activation with potent tumoricidal activities. The ferroptosis-strengthened macrophage regulation strategy present in this study paves the way for TAM-centered antitumoral treatment to overcome the limitations of conventional methods.


Assuntos
Ferroptose , Nanopartículas , Humanos , Macrófagos , Microambiente Tumoral , Macrófagos Associados a Tumor
16.
Bioresour Technol ; 338: 125528, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34284291

RESUMO

The aim of this work was to study the impact of basalt fiber (BF) on hydrogen fermentation of corn straw. The maximum of hydrogen yield and corn straw conversion rate respectively achieved 323.94 mL and 5.23% by adding 1.5 g/L BF particle with the size of 300-400 mesh, which increased by 15.74% and 15.6% respectively than control group. The BF could promote the growth of photosynthetic bacteria, subsequently influencing the products distribution and hydrogen generation. Overall, this investigation demonstrated that BF addition is an effective way to enhance biohydrogen production from corn straw.


Assuntos
Hidrogênio , Zea mays , Fermentação , Silicatos
17.
Trends Genet ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34218958
18.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209353

RESUMO

Acoustic metamaterials are materials with artificially designed structures, which have characteristics that surpass the behavior of natural materials, such as negative refraction, anomalous Doppler effect, plane focusing, etc. This article mainly introduces and summarizes the related research progress of acoustic metamaterials in the past two decades, focusing on meta-atomic acoustic metamaterials, metamolecular acoustic metamaterials, meta-atomic clusters and metamolecule cluster acoustic metamaterials. Finally, the research overview and development trend of acoustic metasurfaces are briefly introduced.

19.
Opt Lett ; 46(14): 3444-3447, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264234

RESUMO

We experimentally investigate the tunable Doppler shift in an 80 nm thick indium-tin-oxide (ITO) film at its epsilon-near-zero (ENZ) region. Under strong and pulsed excitation, ITO exhibits a time-varying change in the refractive index. A maximum frequency redshift of 1.8 THz is observed in the reflected light when the pump light has a peak intensity of ∼140GW/cm2 and a pulse duration of ∼580fs, at an incident angle of 40°. The frequency shift increases with the increase in pump intensity and saturates at the intensity of ∼140GW/cm2. When the pump pulse duration increases from ∼580fs to ∼1380fs, the maximum attainable frequency shift decreases from 1.8 THz to 0.7 THz. In addition, the pump energy required to saturate the frequency shift decreases with the increase in pump pulse duration for ∼x<1ps and remains unchanged for ∼x>1ps durations. Tunability exists among the pump pulse energy, duration, and incident angle for the Doppler shift of the ITO-ENZ material, which can be employed to design efficient frequency shifters for telecom applications.

20.
Biotechnol Adv ; : 107808, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34324993

RESUMO

Enzymes catalyse target reactions under mild conditions with high efficiency, as well as excellent regional-, stereo-, and enantiomeric selectivity. Photocatalysis utilises sustainable and environment-friendly light power to realise efficient chemical conversion. By combining the interdisciplinary advantages of photo- and enzymatic catalysis, the photocatalyst-enzyme hybrid systems have proceeded various light-driven biotransformation with high efficiency under environmentally benign conditions, thus, attracting unparalleled focus during the last decades. It has also been regarded as a promising pathway towards green chemistry utilising ubiquitous solar energy. This systematic review gives insight into this research field by classifying the existing photocatalyst-enzyme hybrid systems into three sections based on different hybridizing modes between photo- and enzymatic catalysis. Furthermore, existing challenges and proposed strategies are discussed within this context. The first system summarised is the cofactor-mediated hybrid system, in which natural/artificial cofactors act as reducing equivalents that connect photocatalysts with enzymes for light-driven enzymatic biotransformation. Second, the direct contact-based photocatalyst-enzyme hybrid systems are described, including two different kinds of electron exchange sites on the enzyme molecules. Third, some cases where photocatalysts and enzymes are integrated into a reaction cascade with specific intermediates will be discussed in the following chapter. Finally, we provide perspective concerning the future of this field.

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