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Infections with methicillin-resistant Staphylococcus aureus(MRSA) are becoming increasingly serious, making the development of novel antimicrobials urgent. Here, we synthesized some amphiphilic honokiol derivatives bearing an oxazole moiety and investigated their antibacterial and hemolytic activities. Bioactivity evaluation showed that E17possessed significant in vitroantibacterial activity against S. aureusand MRSA, along with low hemolytic activity. Moreover, E17exhibited rapid bactericidal properties and was not susceptible to resistance. Mechanistic studies indicated that E17interacts with phosphatidylglycerol and cardiolipin of bacterial cell membranes, leading to changes in cell membrane permeability and polarization, increased intracellular ROS, and leakage of DNA and proteins, thus accelerating bacterial death. Transcriptome analysis further demonstrated that E17has membrane-targeting effects, affecting the expression of genes related to cell membranes and ABC transporter proteins. Notably, in vivoactivity showed that E17has prominent anti-MRSA efficacy, comparable to vancomycin, and is expected to be a new anti-MRSA drug candidate.

Mixtures of shell-biochar and calcium silicate slag were firstly impregnated with pentaethylenehexamine, and then were mixed with wet flue gas desulfurization gypsum (FGDG) particles to prepare the adsorbents. The results showed that the crystalline water in FGDG slags changed the CO2adsorption mechanisms of the amine groups, and the FGDG modified adsorbents exhibited a comparable cyclic recyclability and the adsorption capacity only decreased by 3.61% up to 12 adsorption/desorption cycles.The crystalline water contained in FGDG is successfully supported on the surfaces of the adsorbent. The adsorbent loaded with 35% of FGDG exhibits a higher adsorption capacity than the adsorbent without FGDG, suggesting that the crystalline water promotes the CO2adsorption performances. It demonstrates a favorable recyclability because its saturated adsorption capacity reduced by 3.61% after twelve adsorption-desorption cycles.

Combined chemoradiotherapy can improve antitumor efficiency and reduce the side effects of monotherapy. In this study, we aimed to construct dendritic peptide-based multifunctional nanoparticles (Au@SPP@DOX) for a prolonged circulation time, enhanced cellular uptake, and targeted cancer therapy. Amphiphilic micelle PEG-polylysine-SA (SPP) is composed of polylysine combined with hydrophilic poly(ethylene glycol) (PEG) and hydrophobic stearic acid (SA). Doxorubicin (DOX) is loaded viathe hydrophilic–hydrophobic interaction of SPP, and gold nanoparticles (AuNPs) are loaded viathe electrostatic interaction with SPP. Au@SPP@DOX showed good biocompatibility and could be successfully accumulated at tumor sites through the enhanced permeability and retention (EPR) effect. Then, lysosomes could be ruptured due to the proton sponge effect. DOX became protonated in response to tumor extracellular acidity and was then released from SPP. Under the action of low-dose radiation, Au@SPP@DOX could promote the production of reactive oxygen species (ROS), increase mitochondrial dysfunction, block cell division, and ultimately promote tumor cell apoptosis to achieve a better antitumor effect. This study highlighted the benefit of chemoradiotherapy and suggested that Au@SPP@DOX might serve as a high-efficiency codelivery system for cancer combination therapy in the future.

Two‐photon excitation (TPE) microscopy with near‐infrared (NIR) emission has emerged as a promising technique for deep‐tissue optical imaging. Recent developments in fluorescence lifetime imaging with long‐lived emission probes have further enhanced the spatial resolution and precision of fluorescence imaging, especially in complex systems with short‐lived background signals. In this study, two innovative lysosome‐targeting probes, Cz‐NA and tCz‐NA, are introduced. These probes offer a combination of advantages, including TPE (λex= 880 nm), NIR emission (λem= 650 nm), and thermally activated delayed fluorescence (TADF) with long‐lived lifetimes (1.05 and 1.71 µs, respectively). These characteristics significantly improve the resolution and signal‐to‐noise ratio in deep‐tissue imaging. By integrating an acousto‐optic modulator (AOM) device with TPE microscopy, the authors successfully applied Cz‐NA in two‐photon excited delayed fluorescence (TPEDF) imaging to track lysosomal adaptation and immune responses to inflammation in mice. This study sheds light on the relationship between lysosome tubulation, innate immune responses, and inflammation in vivo, providing valuable insights for the development of autofluorescence‐free molecular probes in the future. A novel donor‐acceptor‐donor (D‐A‐D) type thermally activated delayed fluorescence (TADF) probe, Cz‐NA, incorporates a lysosome‐targeting component. To address limitations in two‐photon laser frequency, an acousto‐optic modulator is integrated. Cz‐NA is successfully used for two‐photon excited delayed fluorescence (TPEDF) imaging to monitor lysosomal dynamics in activated immune cells, providing insights into immune cell activation and responses, in vitro and in vivo.

Cachexia is a complicated metabolic disorder that is characterize by progressive atrophy of skeletal muscle. Cathepsin K (CTSK) is a widely expressed cysteine protease that has garnered attention because of its enzymatic and non‐enzymatic functions in signalling in various pathological conditions. Here, we examined whether CTSK participates in cancer‐induced skeletal muscle loss and dysfunction, focusing on protein metabolic imbalance. Male 9‐week‐old wild‐type (CTSK+/+, n= 10) and CTSK‐knockout (CTSK−/−, n= 10) mice were injected subcutaneously with Lewis lung carcinoma cells (LLC; 5 × 105) or saline, respectively. The mice were then subjected to muscle mass and muscle function measurements. HE staining, immunostaining, quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and western blotting were used to explore the CTSK expression and IRS1/Akt pathway in the gastrocnemius muscle at various time points. In vitromeasurements included CTSK expression, IRS1/Akt pathway‐related target molecule expressions, and the diameter of C2C12 myotubes with or without LLC‐conditioned medium (LCM). An IRS1 ubiquitin assay, and truncation, co‐immunoprecipitation, and co‐localization experiments were also performed. CTSK+/+cachectic animals exhibited loss of skeletal muscle mass (muscle weight loss of 15%, n= 10, P< 0.01), muscle dysfunction (grip strength loss > 15%, n= 10, P< 0.01), and fibre area (average area reduction > 30%, n= 5, P< 0.01). Compared with that of non‐cachectic CTSK+/+mice, the skeletal muscle of cachectic CTSK+/+mice exhibited greater degradation of insulin receptor substrate 1 (IRS1, P< 0.01). In this setting, cachectic muscles exhibited decreases in the phosphorylation levels of protein kinase B (Akt308, P< 0.01; Akt473, P< 0.05) and anabolic‐related proteins (the mammalian target of rapamycin, P< 0.01) and increased levels of catabolism‐related proteins (muscle RING‐finger protein‐1, P< 0.01; MAFbx1, P< 0.01) in CTSK+/+mice (n= 3). Although there was no difference in LLC tumour growth (n= 10, P= 0.44), CTSK deletion mitigated the IRS1 degradation, loss of the skeletal muscle mass (n= 10, P< 0.01), and dysfunction (n= 10, P< 0.01). In vitro, CTSK silencing prevented the IRS1 ubiquitination and loss of the myotube myosin heavy chain content (P< 0.01) induced by LCM, and these changes were accelerated by CTSK overexpression even without LCM. Immunoprecipitation showed that CTSK selectively acted on IRS1 in the region of amino acids 268 to 574. The results of co‐transfection of IRS1‐N‐FLAG or IRS1‐C‐FLAG with CTSK suggested that CTSK selectively cleaves IRS1 and causes ubiquitination‐related degradation of IRS1. These results demonstrate that CTSK plays a novel role in IRS1 ubiquitination in LLC‐induced muscle wasting, and suggest that CTSK could be an effective therapeutic target for cancer‐related cachexia.

Reducing the dimensionality of layered materials can result in properties distinct from their bulk crystals1–3. However, the emergent properties in atomically thin samples, in particular in metallic monolayer flakes, are often obtained at the expense of other important properties. For example, while Ising superconductivity—where the pairing of electrons with opposite out-of-plane spins from K and K′ valleys leads to an in-plane upper critical field exceeding the Pauli limit—does not occur in bulk NbSe2, it was observed in two-dimensional monolayer flakes4. However, the critical temperature was reduced as compared to bulk crystals4–13. Here we take a different route to control the superconducting properties of NbSe2by intercalating bulk crystals with cations from ionic liquids. This produces Ising superconductivity with a similar critical temperature to the non-intercalated bulk and is more stable than in a monolayer flake. Our angle-resolved photoemission spectroscopy measurements reveal the effectively two-dimensional electronic structure, and a comparison of the experimental electronic structures between intercalated bulk NbSe2and monolayer NbSe2film reveals that the intercalant induces electron doping. This suggests ionic liquid cation intercalation is an effective technique for controlling both the dimensionality and the carrier concentration, allowing tailored properties exceeding both bulk crystals and monolayer samples.

ABSTRACTThis research has developed a method for rapid detection of SARS-CoV-2 N protein on a paper-based microfluidic chip. The chitosan-glutaraldehyde cross-linking method is used to fix the coated antibody, and the sandwich enzyme-linked immunosorbent method is used to achieve the specific detection of the target antigen. The system studied the influence of coating antibody concentration and enzyme-labeled antibody concentration on target antigen detection. According to the average gray value measured under different N protein concentrations, the standard curve of the method was established and the sensitivity was tested, and its linear regression was obtained. The equation is y = 9.8286x+137.6, R2 = 0.9772 > 0.90, which shows a high degree of fit. When the concentration of coating antibody and enzyme-labeled antibody were 1 μg/mL and 2 μg/mL, P > 0.05, the difference was not statistically significant, so the lower concentration of 1 μg/mL was chosen as the coating antibody concentration. The results show that the minimum concentration of N protein that can be detected by this method is 8 μg/mL, and the minimum concentration of coating antibody and enzyme-labeled antibody is 1 μg/mL, which has the characteristics of high sensitivity and good repeatability.

The valley depolarization dynamics of free holes in monolayer transition-metal dichalcogenides are studied by solving the Boltzmann transport equation in real time fully ab inito. While monolayer MoSe2, WS2, WSe2, and MoTe2possess long hole valley lifetimes due to the spin-valley locking effect, monolayer MoS2unexpectedly shows ultrafast valley dynamics, with a hole valley lifetime two orders of magnitude shorter than those of the above four materials at room temperature. It is further revealed that the existence of the satellite Γ valley in MoS2provides an additional hole relaxation path where the Γ valley acts as an intermediate in the hole relaxation between primary K′ and K valleys, and moreover, the strong scattering between primary and satellite valleys ensures the ultrafast valley depolarization. By uncovering the pivotal role of the satellite valley, our results may have significant implications for finely controlling valley depolarization in the multivalley materials.

ABSTRACTThis study developed a novel method for the rapid detection of Escherichia coli(E. coli) O157:H7 on a microfluidic platform. First, the concentration of bacteria in a sample was determined with the adenosine triphosphate (ATP) method. Then, the specific detection of E. coliwas achieved in a microfluidic chip by the immune-microsphere technique. The influences of the culture time, flow rate and capture time on the detection of the target bacteria were investigated systematically. Generally, with increasing capture time, more bacteria could be captured by the microspheres, which had a positive effect on bacterial detection. Furthermore, the sensitivity and specificity of the method were also tested. The results showed that this method could specifically detect E. coliwith a sensitivity as high as 49.1 cfu/μL; the consumption of bacteria was 1 μL, and the reagent was at the microliter level. The testing time can be controlled within one and a half hours, and the cost of testing was approximately RMB 10. The method described in this article is simple and accurate and has great application value in bacterial detection for medical diagnostics.

The cellulase cocktail produced by marine Aspergillus nigerexhibits a property of salt-tolerance, which is of great potential in cellulose degradation in high salt environment. In order to explain the mechanism on the salt-tolerance of the cellulase cocktail produced by marine A. niger, six cellulase components (AnCel6, AnCel7A, AnCel7B, AnEGL, AnBGL1 and AnBGL2) were obtained by directed expression. Studies on their enzymatic properties revealed that one β-glucosidase (AnBGL2) and one endoglucanase (AnEGL) exhibited an outstanding salt-tolerant property, and one cellobiohydrolase (AnCel7B) exhibited a certain salt-tolerant property. Subsequent study revealed that the salt-tolerant AnEGL and AnCel7B endowed the cellulase cocktail with stronger salt-tolerant property, while the salt-tolerant AnBGL2 had no positive effect. Moreover, after overexpression of AnCel6, AnCel7A, AnCel7B and AnEGL, the activity of cellulase cocktail increased by 80%, 70%, 63% and 68%, respectively. However, the activity of cellulase cocktail was not improved after overexpression of AnBGL1 and AnBGL2. After mixed-strain fermentation with cellobiohydrolase recombinants (cel6a, cel7aand cel7brecombinants) and endoglucanase recombinant (eglrecombinant), the the activity of cellulase cocktail increased by 114%, 102% and 91%, respectively.

A range of γ-halide/pseudohalide-substituted cyanine-based photosensitizers with programmed levels of singlet oxygen generation capability have been developed as theranostic agents for photodynamic therapy of cancer and infectious diseases.

Water pollution caused by highly toxic Cd(II), Pb(II), and Cr(VI) is a serious problem. In the present work, a green and low-cost adsorbent of g-C3N4nanosheets was developed with superior capacity for both cationic and anionic heavy metals. The adsorbent was easily fabricated through one-step calcination of guanidine hydrochloride with thickness less than 1.6 nm and specific surface area of 111.2 m2·g−1. Kinetic and isotherm studies suggest that the adsorption is an endothermic chemisorption process, occurring on the energetically heterogeneous surface based on a hybrid mechanism of multilayer and monolayer adsorption. The tri-s-triazine units and surface N-containing groups of g-C3N4nanosheets are proposed to be responsible for the adsorption process. Further study on pH demonstrates that electrostatic interaction plays an important role. The maximum adsorption capacity of Cd(II), Pb(II), and Cr(VI) on g-C3N4nanosheets is 123.205 mg·g−1, 136.571 mg·g−1, and 684.451 mg·g−1, respectively. The better adsorption performance of the adsorbent than that of the recently reported nanomaterials and low-cost adsorbents proves its great application potential in the removal of heavy metal contaminants from wastewater. The present paper developed a promising adsorbent which will certainly find applications in wastewater treatment and also provides guiding significance in designing adsorption processes.

Two pilot-scale biological nutrient removal bioreactors were operated side by side under selected flow rate conditions. One reactor was operated under an integrated fixed-film activated sludge (IFAS) reactor configuration, and the second reactor was operated under a conventional activated sludge reactor configuration. The relatively high dissolved oxygen (DO) and low food-to-microorganism ratio created a favourable environment for the proliferation of redworm identified as Aeolosoma hemprichiin the IFAS reactor from day 116, which led to significant deterioration on ammonia removal in the IFAS reactor. The removal efficiencies of chemical oxygen demand (COD) and phosphorus were not significantly affected by the redworm bloom. Several strategies were applied to eliminate the redworms from the IFAS reactor. The most effective strategy was shutting off the DO supply in the aerobic zone and stopping the influent feed for 48 h. Finally, it took about 1·5 months for the IFAS reactor to recover from performing the worm elimination strategy.

The effect of phosphate on anaerobic ammonium oxidation (anammox) was investigated in an integrated fixed film activated sludge-sequencing batch reactor (IFAS-SBR) treating raw digester sludge thickening lagoon supernatants before and after Ostara® treatment (for phosphorus recovery). At a similar nitrogen loading rate (NLR) of 0.31 kg N m−3d−1, pre-Ostara® lagoon supernatant feeding (with a phosphorus concentration of 235 ± 15.4 mg PO43-P L−1) adversely impacted anammox activities, which were significantly improved from 55 ± 9.8% to 88.2 ± 3.6% when post-Ostara® feeding (with a phosphorus concentration of 32 ± 5.4 mg PO43-P L−1) was applied. A higher nitrogen removal rate of 0.30 ± 0.01 kg N m−3d−1was achieved with the post-Ostara® feeding compared to that with the pre-Ostara® feeding. Batch experiments confirmed that the phosphate concentration was the major inhibitor of anammox bacteria, and that anammox bacteria in biofilms showed greater tolerance to phosphate stress than anammox bacteria in flocs. Nitritation–anammox was successfully applied with 100% raw post-Ostara® supernatant feeding and intermittent aeration. High throughput sequencing indicated that the dominant ammonium oxidizing bacteria (AOB) in the IFAS-SBR, Nitrosomonas, facilitated nitritation, and that Candidatus Brocadiawas the dominant bacteria responsible for the anaerobic ammonia oxidation observed. Compared to pre-Ostara® feeding, post-Ostara® feeding facilitated greater relative abundance of anammox bacteria. The highest abundance of Nitrosomonasand Candidatus Brocadiawas 4.2% and 13.9%, respectively, which was observed in the reactor with the post-Ostara® feeding.

Enzyme-activated fluorogenic probes, which invoke enzymatic catalysis to trigger the generation of fluorescence, provide a versatile platform for monitoring biological processes. The development of fluorogenic probes that can readily penetrate the cell envelopes of bacteria are essential to examine intracellular targets of live bacterial cells. Herein, we present the design, synthesis, properties, and biological applications of two series of fluorogenic probes based on cyanine 5 for identification of bacterial nitroreductase (NTR). The selected fluorogenic probe 3generates a rapid 10-fold fluorescence response after being catalytically reduced by NTR to the intermediate para-aminobenzyl substituted which then underwent a rearrangement elimination reaction. Moreover, probe 3is cell permeable for both Gram-positive and Gram-negative bacterial cell envelopes and is selective for NTR over other biological analytes, thus minimizing the background signal and enabling the real-time intracellular imaging of NTR in live bacterial cells.

Aim To evaluate the diagnostic value of serum cancer antigen (CA)125, CA19-9 and CA15-3 concentrations in endometriosis.Methods Case–control studies evaluating CA125, CA19-9 and CA15-3 and endometriosis, published between January 2000 and November 2014 were retrieved from PubMed® and Google Scholar. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Subgroup analyses were carried out by ethnicity and disease stage (early, stage I/II; advanced, stage III/IV).Results The analysis included 12 case–control studies (963 cases, 855 controls). CA125 was associated with endometriosis in the overall population (SMD 0.82, 95% CI 0.72, 0.92), Caucasian subgroup (SMD 1.08, 95% CI 0.96, 1.19), and early (SMD 1.20, 95% CI 0.93, 1.48) or advanced disease (SMD 1.29, 95% CI 1.04, 1.55). CA19-9 was associated with endometriosis in the overall population (SMD 0.48, 95% CI 0.24, 0.72), Caucasian subgroup (SMD 0.31, 95% CI 0.07, 0.55), Asian subgroup (SMD 9.65, 95% CI 7.88, 11.42) and advanced disease (SMD 0.60, 95% CI 0.34, 0.87). CA15-3 was significantly associated with advanced disease (SMD 0.47, 95% CI 0.09, 0.84).Conclusions Serum CA125 and CA19-9 may represent useful biomarkers for the noninvasive diagnosis of endometriosis.