ICAT-Mediated Crosstalk Between Cervical Cancer Cells and Macrophages Promotes M2-Like Macrophage Polarization to Reinforce Tumor Malignant Behaviors.

Inhibitor of ß-catenin and T-cell factor (ICAT) is a classical inhibitor of the Wnt signaling pathway. Nonetheless, our previous work found that ICAT is overexpressed in cervical cancer (CC), resulting in the augmentation of migration and invasion capabilities of CC cells. It remains unclear what molecular mechanism underlies this phenomenon. The interaction between cancer cells and the tumor microenvironment (TME) promotes the outgrowth and metastasis of tumors. Tumor-associated macrophages (TAMs) are a major constituent of the TME and have a significant impact on the advancement of CC. Consequently, our inquiry pertains to the potential of ICAT to facilitate tumor development through its modulation of the cervical TME. In this study, we first verified that ICAT regulated the secretion of cytokines interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in CC cells, leading to M2-like macrophage polarization and enhancement of the migration and invasion of CC cells. Furthermore, the system of co-culturing human umbilical vein endothelial cells (HUVECs) with macrophages revealed that depending on the CC cells' overexpression or inhibition of ICAT, the vascular tube formation by HUVECs can be either increased or decreased. Overall, our study indicates that ICAT stimulates M2-like polarization of TAMs via upregulating IL-10 and TGF-ß, which results in increased neovascularization, tumor metastasis, and immunosuppression in CC. In upcoming times, inhibiting crosstalk between CC cells and TAMs may be a possible strategy for CC therapy.

Overlooked Complexation and Competition Effects of Phenolic Contaminants in a Mn(II)/Nitrilotriacetic Acid/Peroxymonosulfate System: Inhibited Generation of Primary and Secondary High-Valent Manganese Species.

Organic contaminants with lower Hammett constants are typically more prone to being attacked by reactive oxygen species (ROS) in advanced oxidation processes (AOPs). However, the interactions of an organic contaminant with catalytic centers and participating ROS are complex and lack an in-depth understanding. In this work, we observed an abnormal phenomenon in AOPs that the degradation of electron-rich phenolics, such as 4-methoxyphenol, acetaminophen, and 4-presol, was unexpectedly slower than electron-deficient phenolics in a Mn(II)/nitrilotriacetic acid/peroxymonosulfate (Mn(II)/NTA/PMS) system. The established quantitative structure-activity relationship revealed a volcano-type dependence of the degradation rates on the Hammett constants of pollutants. Leveraging substantial analytical techniques and modeling analysis, we concluded that the electron-rich phenolics would inhibit the generation of both primary (Mn(III)NTA) and secondary (Mn(V)NTA) high-valent manganese species through complexation and competition effects. Specifically, the electron-rich phenolics would form a hydrogen bond with Mn(II)/NTA/PMS through outer-sphere interactions, thereby reducing the electrophilic reactivity of PMS to accept the electron transfer from Mn(II)NTA, and slowing down the generation of reactive Mn(III)NTA. Furthermore, the generated Mn(III)NTA is more inclined to react with electron-rich phenolics than PMS due to their higher reaction rate constants (8314 ± 440, 6372 ± 146, and 6919 ± 31 M-1 s-1 for 4-methoxyphenol, acetaminophen, and 4-presol, respectively, as compared with 671 M-1 s-1 for PMS). Consequently, the two-stage inhibition impeded the generation of Mn(V)NTA. In contrast, the complexation and competition effects are insignificant for electron-deficient phenolics, leading to declined reaction rates when the Hammett constants of pollutants increase. For practical applications, such complexation and competition effects would cause the degradation of electron-rich phenolics to be more susceptible to water matrixes, whereas the degradation of electron-deficient phenolics remains largely unaffected. Overall, this study elucidated the intricate interaction mechanisms between contaminants and reactive metal species at both the electronic and kinetic levels, further illuminating their implications for practical treatment.

Carbon chain elongation characterizations of electrode-biofilm microbes in electro-fermentation.

The higher efficiency of electro-fermentation in synthesizing medium-chain fatty acids (MCFAs) compared to traditional fermentation has been acknowledged. However, the functional mechanisms of electrode-biofilm enhancing MCFAs synthesis remain research gaps. To address this, this study proposed a continuous flow electrode-biofilm reactor for chain elongation (CE). After 225 days of operation, stable electrode-biofilms formed and notably improved caproate yield by more than 38 %. The electrode-biofilm was enriched with more CE microorganisms and electroactive bacteria compared to the suspended sludge microorganisms, including Caproicibacterium, Oscillibacter and Pseudoramibacter. Besides, the upregulated CE pathways were evaluated by metagenomic analysis, and the results indicated that the pathways such as acetyl-CoA and malonyl-[acp] formation, reverse beta-oxidation, and fatty acid biosynthesis pathway were all markedly enhanced in cathodic biofilm, more than anodic biofilm and suspended microorganisms. Moreover, microbial community regulated processes like bacterial chemotaxis, flagellar assembly and quorum sensing, crucial for electrode-biofilm formation. Electron transfer, energy metabolism, and microbial interactions were found to be prominently upregulated in the cathodic biofilm, surpassing levels observed in anodic biofilm and suspended sludge microorganisms, which further enhanced CE efficiency. In addition, the statistical analyses further highlighted key microbial functions and interactions within the cathodic biofilm. Oscillospiraceae_bacterium was identified to be the most active microbe, alongside pivotal roles played by Caproiciproducens_sp._NJN-50, Clostridiales_bacterium, Prevotella_sp. and Pseudoclavibacter_caeni. Eventually, the proposed microbial collaboration mechanisms of cathodic biofilm were ascertained. Overall, this study uncovered the biological effects of the electrode-biofilm on MCFAs electrosynthesis, thereby advancing biochemicals production and filling the knowledge gaps in CE electroactive biofilm reactors.

Electron Collimation in Twisted Bilayer Graphene via Gate-Defined Moiré Barriers.

Electron collimation via a graphene p-n junction allows electrostatic control of ballistic electron trajectories akin to that of an optical circuit. Similar manipulation of novel correlated electronic phases in twisted-bilayer graphene (tBLG) can provide additional probes to the underlying physics and device components toward advanced quantum electronics. In this work, we demonstrate collimation of the electron flow via gate-defined moiré barriers in a tBLG device, utilizing the band-insulator gap of the moiré superlattice. A single junction can be tuned to host a chosen combination of conventional pseudo barrier and moiré tunnel barriers, from which we demonstrate improved collimation efficiency. By measuring transport through two consecutive moiré collimators separated by 1 µm, we demonstrate evidence of electron collimation in tBLG in the presence of realistic twist-angle inhomogeneity.

Detection of egg white allergy in children by specific IgE microarray chemiluminescence immunoassay.

BACKGROUND: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children. METHODS: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system. RESULTS: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R2 > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease. CONCLUSIONS: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children.

Effect of omentum preservation on long-term prognosis of locally advanced gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The effect of omentum preservation (OP) on locally advanced gastric cancer (LAGC) remains controversial. This study aimed to investigate the long-term prognosis of LAGC patients with OP versus omentum resection (OR). METHODS: A comprehensive search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted up until February 2024. Statistical analysis was performed using Stata 12.0 software. The primary outcome was to assess the impact of OP on the long-term prognosis of patients with LAGC, including overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of six case-control studies were included, encompassing a cohort of 1897 patients. The OP group consisted of 844 patients, while the OR group comprised 1053 patients. The study results showed that the OS (HR = 0.72, 95% CI: 0.58-0.90, P = 0.003) and 5-year RFS (HR = 0.79, 95% CI: 0.63-0.99, P = 0.038) in the OP group were superior to those observed in the OR group. Subgroup analysis indicated that 5-year OS (HR = 0.64, P = 0.003) and 5-year RFS (HR = 0.69, P = 0.005) in the OP group were also better than those in the OR group in Korea. However, the subgroup analysis conducted on stage T3-T4 tumors revealed no statistically significant differences in OS (P = 0.083) and 5-year RFS (P = 0.173) between the two groups. CONCLUSION: Compared with OR, OP shows non-inferiority in patients with LAGC and can be considered a potential treatment option for radical gastrectomy.

Wavelength modulation spectroscopy of nitric oxide using a quantum cascade laser in intermittent continuous wave operation.

Operating quantum cascade lasers (QCLs) in intermittent continuous wave (iCW) shows the merit of a broader frequency tuning range and lower heat dissipation compared to the continuous wave (CW) operation. We demonstrate for the first time wavelength modulation spectroscopy (WMS) of a QCL in iCW operation for sensitive gas detection. A strong absorption line of nitric oxide (NO) at 5.18 µm is exploited by a QCL in iCW mode, which periodically switches off the QCL between individual laser scans. The generated thermal chirp dominates the laser frequency tuning, resulting in a broader spectral coverage of more than 2 cm-1 at a scanning rate of 1 kHz. In addition, a high-frequency dither (50 kHz) is supposed onto this iCW injection current to introduce the harmonic signals that arise from gas absorption. At the WMS-iCW operation of the QCL, we have obtained a minimum detection limit of 4.5 ppb at an averaging time of 80 s, which is improved significantly compared to 130 ppb achieved by direct absorption spectroscopy at the same averaging time using the identical optical setup, without external forced air- or water-cooling. Our method provides a promising method for sensor miniaturization and field application.

The Role of the Mu Opioid Receptors of the Medial Prefrontal Cortex in the Modulation of Analgesia Induced by Acute Restraint Stress in Male Mice.

Mu opioid receptors (MORs) represent a vital mechanism related to the modulation of stress-induced analgesia (SIA). Previous studies have reported on the gamma-aminobutyric acid (GABA)ergic "disinhibition" mechanisms of MORs on the descending pain modulatory pathway of SIA induced in the midbrain. However, the role of the MORs expressed in the medial prefrontal cortex (mPFC), one of the main cortical areas participating in pain modulation, in SIA remains completely unknown. In this study, we investigated the contributions of MORs expressed on glutamatergic (MORGlut) and GABAergic (MORGABA) neurons of the medial prefrontal cortex (mPFC), as well as the functional role and activity of neurons projecting from the mPFC to the periaqueductal gray (PAG) region, in male mice. We achieved this through a combination of hot-plate tests, c-fos staining, and 1 h acute restraint stress exposure tests. The results showed that our acute restraint stress protocol produced mPFC MOR-dependent SIA effects. In particular, MORGABA was found to play a major role in modulating the effects of SIA, whereas MORGlut seemed to be unconnected to the process. We also found that mPFC-PAG projections were efficiently activated and played key roles in the effects of SIA, and their activation was mediated by MORGABA to a large extent. These results indicated that the activation of mPFC MORGABA due to restraint stress was able to activate mPFC-PAG projections in a potential "disinhibition" pathway that produced analgesic effects. These findings provide a potential theoretical basis for pain treatment or drug screening targeting the mPFC.

Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency. / åŒè†¦é ¸ç›åœ¨æˆäººç”Ÿé•¿æ¿€ç´ ç¼ºä¹æ‰€è‡´éª¨è´¨ç–æ¾ç—‡ä¸­çš„ä½œç”¨ï¼ˆè‹±æ–‡ï¼‰.

In recent years, growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling, crucial for maintaining healthy bone mass throughout life. Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling, significantly affecting bone microarchitecture and increasing fracture risk. Although recombinant human growth hormone replacement therapy can mitigate these adverse effects, improving bone density, and reduce fracture risk, its effectiveness in treating osteoporosis, especially in adults with established growth hormone deficiency, seems limited. Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts, and clinical trials have confirmed their efficacy in improving osteoporosis. Therefore, for adult growth hormone deficiency patients with osteoporosis, the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Disrupted Human-Dog Interbrain Neural Coupling in Autism-Associated Shank3 Mutant Dogs.

Dogs interact with humans effectively and intimately. However, the neural underpinnings for such interspecies social communication are not understood. It is known that interbrain activity coupling, i.e., the synchronization of neural activity between individuals, represents the neural basis of social interactions. Here, previously unknown cross-species interbrain activity coupling in interacting human-dog dyads is reported. By analyzing electroencephalography signals from both dogs and humans, it is found that mutual gaze and petting induce interbrain synchronization in the frontal and parietal regions of the human-dog dyads, respectively. The strength of the synchronization increases with growing familiarity of the human-dog dyad over five days, and the information flow analysis suggests that the human is the leader while the dog is the follower during human-dog interactions. Furthermore, dogs with Shank3 mutations, which represent a promising complementary animal model of autism spectrum disorders (ASD), show a loss of interbrain coupling and reduced attention during human-dog interactions. Such abnormalities are rescued by the psychedelic lysergic acid diethylamide (LSD). The results reveal previously unknown interbrain synchronizations within an interacting human-dog dyad which may underlie the interspecies communication, and suggest a potential of LSD for the amelioration of social impairment in patients with ASD.

Improvement of the Abrasion and Corrosion Resistance of a Waterborne Epoxy Coating by α-ZrP@PTA-Ce(III) with Dual Corrosion Inhibition Effects.

The introduction of poly(tannic acid) (PTA) and cerium ion [Ce(III)] on the surface of α-zirconium phosphate (α-ZrP) endowed the α-ZrP@PTA-Ce(III)/waterborne epoxy composite coating with enhanced corrosion protection and wear resistance performances. The successful preparation of α-ZrP@PTA-Ce(III) was confirmed through X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectra. PTA improved the compatibility between α-ZrP@PTA-Ce(III) and the waterborne epoxy resin due to the presence of organic groups from tannic acid. The wear resistance test indicated that the incorporation of α-ZrP@PTA-Ce(III) effectively reduced the coefficient of friction and the wear rate. Electrochemical impedance spectroscopy was used to analyze the corrosion protection performance of unbroken coatings and the self-healing ability of scratched coatings. The incorporation of α-ZrP@PTA-Ce(III) improved the protection performace distinctly. In addition, α-ZrP@PTA-Ce(III) endowed the composite coating with dual corrosion inhibition effects, originating from the PTA film, to prevent the penetration of corrosive media and a dense film that came from the Ce(III) cation. The waterborne epoxy system with enhanced corrosion and wear resistance in this paper broadens the application of α-ZrP.

Easy-to-configure zero-dimensional valley-chiral modes in a graphene point junction.

The valley degree of freedom in two-dimensional (2D) materials can be manipulated for low-dissipation quantum electronics called valleytronics. At the boundary between two regions of bilayer graphene with different atomic or electrostatic configuration, valley-polarized current has been realized. However, the demanding fabrication and operation requirements limit device reproducibility and scalability toward more advanced valleytronics circuits. We demonstrate a device architecture of a point junction where a valley-chiral 0D PN junction is easily configured, switchable, and capable of carrying valley current with an estimated polarization of ~80%. This work provides a building block in manipulating valley quantum numbers and scalable valleytronics.

Ultrahigh Electrostrictive Effect in Lead-Free Sodium Bismuth Titanate-Based Relaxor Ferroelectric Thick Film.

In recent years, the development of environmentally friendly, lead-free ferroelectric films with prominent electrostrictive effects have been a key area of focus due to their potential applications in micro-actuators, sensors, and transducers for advanced microelectromechanical systems (MEMS). This work investigated the enhanced electrostrictive effect in lead-free sodium bismuth titanate-based relaxor ferroelectric films. The films, composed of (Bi0.5Na0.5)0.8-xBaxSr0.2TiO3 (BNBST, x = 0.02, 0.06, and 0.11), with thickness around 1 µm, were prepared using a sol-gel method on Pt/TiO2/SiO2/Si substrates. By varying the Ba2+ content, the crystal structure, morphology, and electrical properties, including dielectric, ferroelectric, strain, and electromechanical performance, were investigated. The films exhibited a single pseudocubic structure without preferred orientation. A remarkable strain response (S > 0.24%) was obtained in the films (x = 0.02, 0.06) with the coexistence of nonergodic and ergodic relaxor phases. Further, in the x = 0.11 thick films with an ergodic relaxor state, an ultrahigh electrostrictive coefficient Q of 0.32 m4/C2 was achieved. These findings highlight the potential of BNBST films as high-performance, environmentally friendly electrostrictive films for advanced microelectromechanical systems (MEMS) and electronic devices.

IL13RA2 promotes progression of infantile haemangioma by activating glycolysis and the Wnt/ß-catenin signaling pathway.

Background: Interleukin 13 receptor subunit alpha 2 (IL13RA2) plays an essential role in the progression of many cancers. However, the role of IL13RA2 in infantile haemangioma (IH) is still unknown. Materials and Methods: IL13RA2 expression in IH tissues was analyzed using western blot, qRT-PCR, and immunofluorescence. The role of IL13RA2 in haemangioma-derived endothelial cells (HemECs) was determined following knockdown or overexpression of IL13RA2 using CCK-8, colony formation, apoptosis, wound healing, tubule formation, Transwell, and western blot. Results: IL13RA2 expression was upregulated in IH tissues. IL13RA2 overexpression promoted proliferation, migration, and invasion of HemECs and induced glycolysis, which was confirmed with a glycolysis inhibitor. Specifically, IL13RA2 interacted with ß-catenin and activated the Wnt/ß-catenin pathway in HemECs, which were involved in the above-mentioned effects of IL13RA2. Conclusions: These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.

Characterization and discrimination of donkey milk lipids and volatiles across lactation stages.

The lipid and flavor in milk are key factors that affect its quality, which profiles during donkey lactation are not yet clear. In this study, the lipids and volatile compounds (VOCs) in donkey milk from stages of lactation were analyzed by using LC-MS and GC-IMS. A total of 1774 lipids were identified in donkey milk, spanning over 6 major categories and attributed to 30 subclasses. The 233 differentially expressed lipids were identified between donkey colostrum and mature milk, which participate in 20 metabolic pathways, including glycerophospholipid, linoleic acid, and sphingolipid. Additionally, 35 VOCs in donkey milk were identified, including 28.57% aldehydes, 28.57% ketones, 25.71% esters, and 8.57% alcohols. Of these VOCs, 15 were determined to be characteristic flavors in donkey milk, mainly including methyl 2-methylbutanoate, 2-pentanone, and butyl acetate. 11 significantly different VOCs were found between the groups. Acetone, 2-heptanone, and ethyl acetate-m were considered potential discriminatory markers.

Impedance matching in optically induced dielectrophoresis: Effect of medium conductivity on trapping force.

An impedance analysis for optically induced dielectrophoresis is presented. A circuit model is developed for this purpose. The model parameters are fully defined in terms of the geometrical and material properties of the system. It is shown that trapping force can only be generated when the material properties follow certain impedance matching conditions. The impedance match factor is introduced to succinctly quantify the phenomenon. It is used to calculate bounds on the allowed electrical conductivity of the suspension medium. Results from the proposed model are found to be in good agreement with full-wave numerical simulations. By computing the acceptable set of material parameters with little computational cost, the presented analysis can streamline ODEP system design for various applications.

Angiotensin II depends on hippo/YAP signaling to reprogram angiogenesis and promote liver fibrosis.

Liver fibrosis is a chronic pathological process in which the abnormal proliferation of connective tissue is induced by various pathogenic factors. During the process of fibrosis, excessive angiogenesis is observed. Physiological angiogenesis has the potential to impede the progression of liver fibrosis through augmenting matrix metalloenzyme activity; however, pathological angiogenesis can exacerbate liver fibrosis by promoting collagen accumulation. Therefore, a key scientific research focus in the treatment of liver diseases is to search for the "on-off" mechanism that regulates angiogenesis from normal proliferation to pathological proliferation. In this study, we found that excessive angiogenesis appeared during the initial phase of hepatic fibrosis without mesenchymal characteristics. In addition, angiogenesis accompanied by significant endothelial-to-mesenchymal transition (EndMT) was observed in mice after the intraperitoneal injection of angiotensin II (Ang II). Interestingly, the changes in Yes-associated protein (YAP) activity in endothelial cells (ECs) can affect the regulation of angiogenesis by Ang II. The results of in vitro experiments revealed that the regulatory influence of Ang II on ECs was significantly attenuated upon suppression of YAP activity. Furthermore, the function of Ang II in regulating angiogenesis during fibrosis was investigated in liver-specific transgenic mice. The results revealed that Ang II gene deletion could restrain liver fibrosis and EndMT. Meanwhile, Ang II deletion downregulated the profibrotic YAP signaling pathway in ECs. The small molecule AT1R agonist olmesartan targeting Ang II-YAP signaling could also alleviate liver fibrosis. In conclusion, this study identified Ang II as a pivotal regulator of EndMT during the progression of liver fibrosis and evaluated the therapeutic effect of the Ang II-targeted drug olmesartan on liver fibrosis.

Left atrial appendage thrombus is associated with a higher fractal dimension in patients with atrial fibrillation.

PURPOSE: To assess the anatomical complexity of the left atrial appendage (LAA) using fractal dimension (FD) based on cardiac computed tomography angiography (CTA) and the association between LAA FD and LAA thrombosis. MATERIALS AND METHODS: Patients with atrial fibrillation (AF) who underwent both cardiac CTA and transesophageal echocardiography (TEE) between December 2018 and December 2022 were retrospectively analyzed. Patients were categorized into normal (n = 925), circulatory stasis (n = 82), and thrombus groups (n = 76) based on TEE results and propensity score matching (PSM) was performed for subsequent analysis. FD was calculated to quantify the morphological heterogeneity of LAA. Independent risk factors for thrombus were screened using logistic regression. The diagnostic performance of FD and CHA2DS2-VaSc score for predicting thrombus was evaluated using the area under the receiver operating characteristics curve (AUC). RESULTS: LAA FD was higher in the thrombus group (1.61 [1.49, 1.70], P < 0.001) than in the circulatory stasis (1.33 [1.18, 1.47]) and normal groups (1.30 [1.18, 1.42]) both before and after PSM. LAA FD was also an independent risk factor in the thrombus (OR [odds ratio] = 570,861.15 compared to normal, 41,122.87 compared to circulatory stasis; all P < 0.001) and circulatory stasis group (OR = 98.87, P = 0.001) after PSM. The diagnostic performance of LAA FD was significantly better than the CHA2DS2-VaSc score in identifying thrombus. CONCLUSIONS: Patients with high LAA FD are more likely to develop LAA thrombus, and the use of FD provides an effective method for assessing the risk of thrombosis in AF patients, thereby guiding individualized clinical treatment.