Bio-orthogonally Activatable Fluorescent Probe for Specific Imaging of Myeloid Cell Leukemia 1 Protein.

The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) has been increasingly identified as a promising potential therapeutic target attributed to its critical regulation effect in diverse cellar physiopathological events. Current fluorescence imaging strategies tend to be susceptible to the cellular microenvironment, and straightforward mapping of Mcl-1's level variation remains challenging. In this paper, an activatable "off-on" fluorescence strategy for Mcl-1 specific labeling was presented based on bio-orthogonal chemistry by introducing tetrazine-functionalized borondipyrromethene (TB) as a fluorescent reporter and trans-cyclooctyne-derived indole-2-carboxylic acid (TI) as an Mcl-1 targeting moiety. With the click pair of TB and TI, the Mcl-1 expression level in vitro and in vivo was successfully mapped straightforward. Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.

Performance analysis of an all-optical double-hop free-space optical communication system considering fiber coupling.

In an all-optical double-hop free-space optical communication system, the outage probability and bit error rate are analyzed using a composite channel. The model involves atmospheric attenuation, atmospheric turbulence, pointing error, and fiber coupling efficiency. Based on analysis of the channel model and amplifier spontaneous emission noise, the outage probability and bit error rate are obtained. For an all-optical double-hop link, fiber coupling efficiency has an important impact on outage probability, especially at relatively short total link length. By compensating for three terms of wavefront distortions, the system outage probability significantly decreases. The communication performance is further improved by optimizing the receiving aperture diameter and beam width.

Analysis and evaluation of the performance between reciprocity and time delay in the atmospheric turbulence channel.

In order to better evaluate the relationship between reciprocity and time delay of the fiber receiving system in the atmospheric turbulence channel, a time-domain signal generation mathematical model is proposed for the first time. A numerical solution of Johnson SB probability density distribution (PDF) in time-domain is creatively given for evaluating the reciprocity of both communication ends, which relates to the normalized fluctuation variance of the light intensity and the Greenwood frequency. An experiment is then carried out for verifying the time-domain signal generation model and measuring reciprocity. It shows that the excellent fitting accuracy of Johnson SB PDF signal generation model is first experimentally verified. It also indicates that the system reciprocity is improved by 10% after eliminating the system time delay. Meanwhile, the relationship between time delay and reciprocity under different atmospheric environments are analyzed and the relationship between time delay and system reciprocity at different Greenwood frequencies are discussed. This work provides a time parameter reference for the design of adaptive system and free-space optical (FSO) communication system.

Performance of M-PAM FSO communication systems in atmospheric turbulence based on APD detector.

We characterize the performance of the optical signal propagation model of multi-level pulse amplitude modulation (M-PAM) based on avalanche photodiode (APD) detector in the free-space link for the first time. When the number of photons absorbed by the active surface of the APD is large enough, the bit error rate (BER) performance relationship of the systems based on the signal intensity and the photon characteristics are depicted. We use the Gamma-Gamma (G-G) channel model to analysis the communication systems with joint parameter constraints, and demonstrate the atmospheric turbulence intensity, link lengths, optical wavelength, symbol transmission rate, temperature of APD and pointing errors (PEs) impact on the system average bit error rate (ABER) performance. Moreover, the relationship between signal-to-noise-ratio (SNR) and ABER rate is given. The numerical results show that the 4-PAM free-space optical (FSO) communication is suitable for medium-to-weak turbulence, and the high gain of APD can mitigate the influence of ABER. The best detection condition of the 4-PAM optical signal is at least 20 dB SNR, when the ABER is under the 7% forward error correction (FEC) limit of 3.8 × 10-3. This work provides a reference for parameter designing and evaluating in M-PAM FSO communication systems.

Phloretin targets SIRT1 to alleviate oxidative stress, apoptosis, and inflammation in deep venous thrombosis.

Deep vein thrombosis (DVT) is a type of venous thromboembolism posing a serious threat to health on a global scale. Phloretin is a potential natural product that has a variety of pharmacological activities. Besides, some Chinese medicines reported that deacetylase sirtuin (SIRT)1 treats DVT by anti-inflammatory and anti-platelet production. However, the specific binding targets and binding modes have not been elaborated. The present study was to investigate whether phloretin attenuates DVT in model rats and oxidized low­density lipoprotein (ox­LDL) induced human umbilical vein endothelial cells (HUVECs), and to explore its potential target. The results revealed that the treatment of phloretin, especially pretreatment of it elevated tissue plasminogen activator (t-PA), superoxide dismutase (SOD), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and cell apoptosis proteins whereas it suppressed plasminogen activator inhibitor (PAI), malondialdehyde (MDA), reactive oxygen species (ROS), fibrinogen (FIB) in DVT rats and cells. Concurrently, phloretin inhibited collagen type I alpha 1 (COL1A1), transforming growth factor-ß1 (TGF-ß1), and inflammatory factors while it enhanced nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase 1 (HO-1). In addition, 20 µM phloretin exerted powerful effective protection in HUVECs with DVT model. Later, the surface plasmon resonance (SPR) confirmed that phloretin has a high affinity with SIRT1. Furthermore, siRNA-SIRT1 transfection abolished the protective effect of phloretin against ox­LDL­induced DVT in HUVECs, indicating that phloretin targets SIRT1 to alleviate oxidative stress, cell apoptosis, and inflammation in DVT rats and HUVECs. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00207-y.

Laboratory Evaluation of a Low-Damage Authigenic Mud Acid System for Bai-823 Well Block.

Aiming at the problem of single and poor adaptability of Bai-823 plugging removal system, an authigenic mud acid system using methyl formate, ammonium chloride, and ammonium fluoride as raw materials is proposed, which can adapt to the temperature of 60-80 °C of the target reservoir and sandstone lithology. The acid-generating capacity of the authigenic acid system at different temperatures was evaluated. The results showed that the H+ concentration remained at 3.35 mol/L after 180 min at 80 °C, which indicated that authigenic acid could generate acid continuously and thus be competent for acidizing and plugging removal of further wells. The corrosion rate of authigenic acid to N80 steel was further investigated. When 2 wt % SA1-3B corrosion inhibitor was used, the corrosion rate was only 0.15 g/(m2·h). At the same time, the corrosion capacities of authigenic acid to rock core and scale samples were studied, which were 19.38 and 93.81%, respectively, indicating that the authigenic acid system realized pipeline and reservoir friendliness when it was able to effectively remove plugging. Finally, a core displacement experiment was carried out to simulate reservoir acidizing for plugging removal. The results showed that the core permeability increased from 1.00 to 1.63 after acidizing modification with authigenic acid. All of the above studies show that a kind of authigenic mud acid has been successfully prepared, and a new idea for the authigenic acid system has been proposed.

Evaluation of digestibility differences for apple polyphenolics using in vitro elderly and adult digestion models.

We evaluated the in vitro digestibility of apple polyphenols mimicking elderly and adult digestion models (dynamic and static systems). The digestibility of total apple polyphenols in small intestine was much higher in the adult dynamic system (62 µg/100 g fresh apple) compared to the static system (20 µg/100 g fresh apple) and elderly dynamic digestion conditions (33 µg/100 g fresh apple). Elderly in vitro static digestion showed better antioxidant activity than the adult system (OH and ABTS+ methods). Thus, the in vitro dynamic digestion system can more truly reflect the digestion of apple polyphenols than static digestion system. Moreover, elderly digestion conditions negatively influenced the digestibility of apple polyphenols including chlorogenic acid, epicatechin, phlorizin, rutin, phloretin, hyperoside, proanthocyanidin B2, and quercetin. Hence, appropriate selection of in vitro digestion models for elderly is a prerequisite to exploring the digestibility of phytochemicals for the development of functional food products for elderly.

STAT5 inhibitor attenuates atherosclerosis via inhibition of inflammation: the role of STAT5 in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease driven by lipids, which occurs preferentially in the branches or curved areas of the middle and large arteries, contributing to increased morbidity and mortality of cardiovascular disease. Recently, it has been reported that STAT5 and its regulated immune response are closely related to non-tumor diseases. However, the role of STAT5 in the development of atherosclerosis remains unknown. In this study, atherosclerosis was induced by high-fat diet (HFD) in ApoE-/- mice, and STAT5-IN-1, a STAT5 inhibitor, was orally given. Macrophages stimulated by oxLDL were used as cell models in vitro. The effects of STAT5-IN-1 in ApoE-/- mice induced by HFD were assessed, and the underlying mechanisms were investigated by siRNA-induced gene silencing. The results revealed that treatment with STAT5 inhibitor significantly attenuated atherosclerosis in ApoE-/- mice induced by HFD via decreasing inflammation. Furthermore, it was demonstrated that inhibiting STAT5 could decrease oxLDL-induced inflammation. In summary, STAT5-IN-1 may be a potential drug for the treatment of atherosclerosis, and targeting STAT5 has the ability to be a potential therapeutic strategy for reducing atherosclerosis.

Critical lower extremity ischemia after snakebite: A case report.

BACKGROUND: Globally, the estimated annual incidence of snakebites is approximately 5 million, and approximately 100000 deaths occur from snakebites annually. Local tissue reaction, haemorrhagic clotting disorder, nephrotoxicity, and neurotoxicity are very common effects of snake envenomation, but other rarer complications, such as thrombosis, may also occur as a result of underlying disease. In the treatment of snakebite patients, attention should be paid to the patient's underlying diseases to avoid serious and catastrophic consequences secondary to snakebite. CASE SUMMARY: We report a 69-year-old man with critical right lower extremity pain after left foot snakebite 10 d prior without intermittent claudication or atrial fibrillation history. He was diagnosed with acute right lower extremity arterial thrombosis, which may have been caused by coagulopathy after snakebite and lower extremity atherosclerotic occlusive disease. Lower extremity computed tomography angiography at another hospital revealed that the aortoiliac and femoral arteries had neither filling defects nor atherosclerosis, but the right popliteal artery was occluded 2.3 cm below the tibial plateau. The patient received emergency catheter-directed thrombolysis, but amputation was carried out 11 d after admission because the patient had been admitted to the hospital too late to save the extremity. CONCLUSION: Acute ischaemia of the lower extremity due to snakebite is a rare event, and physicians should bear in mind the serious complications that may occur, especially in patients with atherosclerotic disease.

Effect of lactic acid bacteria fermentation on tannins removal in Xuan Mugua fruits.

The present study was conducted for developing a new method to reduce the tannins content of Xuan Mugua fruits. Lactic acid bacteria fermentation-like incubation was explored as an efficient method to reduce the astringency of Mugua fruits by reducing tannins content. To ensure the efficient removal of tannins, the fermentation conditions were optimized such as temperature, time, and ratio of bacteria to Mugua. Bacteria were able to reduce 78% of the tannins content in Mugua under the optimized conditions as assessed by the methylcellulose perceptible tannins assay. Meanwhile, the active components including polysaccharides, triterpenes, and antioxidants of Mugua with bacterial incubation were also explored, which showed the significant decrease compared to non-fermented Mugua. However, the trend for flavor components was different. This research provides a natural method to solve the astringency problem of these fruits and it will extend their application in food industry.

Peperomin E (PepE) protects against high fat diet-induced atherosclerosis in Apolipoprotein E deficient (ApoE-/-) mice through reducing inflammation via the suppression of NLRP3 signaling pathway.

Peperomin E (PepE) is a type of secolignan, a major component of the plant Peperomia dindygulensis. It has been shown to exert anti-inflammatory effects; however, the effects of PepE on human atherosclerosis remain unexplored. In the study, we investigated the role of PepE in high fat diet (HFD) induced atherosclerosis using apolipoprotein E defcient (ApoE-/-) mice. Elevated serum homocyteine, cholesterol, and triglyceride levels, accelerated progression of atherosclerosis and exacerbated macrophage infiltration into atherosclerotic lesions were observed in HFD-fed ApoE-/- mice, which were attenuated by PepE treatment. ApoE-/- mice fed with HFD exhibited significantly high levels of inflammation-associated regulators in artery tissues, accompanied with an increased expression of p-inhibitor of κBα (IκBα) and p-nuclear factor-kappa B (NF-κB), and the process was blocked by PepE administration. Further, we found NOD-like receptor pyrin 3 (NLRP3) inflammasome activation in artery tissues of HFD-fed ApoE-/- mice. In vitro, silencing NLRP3 using small interfering RNA efficiently inhibited oxidized-low-density lipoprotein (oxLDL)-induced ASC and Caspase-1 expressions, interleukin (IL)-1ß and IL-18 production in human aortic endothelial cells (HAECs). Further experiments indicated that NLRP3-ASC pathway was activated by reactive oxygen species (ROS), since ROS scavenger of N-acetyl-cysteine (NAC) prevented, which was further reduced by PepE addition. However, the anti-inflammatory effects of PepE on oxLDL-incubated HAECs were abolished by over-expression NLRP3. Together, our study revealed that PepE inhibited atherosclerosis development in HFD-fed ApoE-/- mice by suppressing NLRP3 inflammatory signaling pathway, and suggested that PepE might be a potential therapeutic strategy in the prevention of atherosclerosis.

Autophagy regulates proliferation and biliary differentiation of hepatic oval cells via the MAPK/ERK signaling pathway.

Hepatic oval cells (HOCs) are thought to possess self­renewal ability and a bipotential capacity for differentiation, which allows them to differentiate into hepatocytes and cholangiocytes. Autophagy serves an important role in self­renewal and differentiation of stem cells; however, how autophagy contributes to proliferation and differentiation of hepatic progenitor cells has yet to be elucidated. In the present study, autophagy was regulated by rapamycin (Rapa) and chloroquine (Chlo) administration. The results demonstrated that Chlo­treated HOCs exhibited decreased autophagic activity alongside a decreased tendency to proliferate, as determined by Cell Counting Kit­8. In addition, activation of autophagy by Rapa enhanced the biliary differentiation of HOCs. Furthermore, increased phosphorylated (p)­extracellular signal­regulated kinase (ERK)/p­p38 expression was observed following the induction of autophagy, thus indicating that the mitogen­activated protein kinase (MAPK)/ERK signaling pathway was activated by autophagy to exert effects on the stimulation of HOC proliferation and differentiation. In conclusion, the present study demonstrated that autophagy regulates proliferation and biliary differentiation of HOCs via the MAPK/ERK signaling pathway. These results suggest a role for autophagy in stimulating the proliferation and differentiation of HOCs.