Esterase-Activated, pH-Responsive, and Genetically Targetable Nano-Prodrug for Cancer Cell Photo-Ablation.

Activatable prodrugs have drawn considerable attention for cancer cell ablation owing to their high specificity in drug delivery systems. However, phototheranostic prodrugs with dual organelle-targeting and synergistic effects are still rare due to low intelligence of their structures. Besides, the cell membrane, exocytosis, and diffusional hindrance by the extracellular matrix reduce drug uptake. Moreover, the up-regulation of heat shock protein and short singlet-oxygen lifetime in cancer cells hamper photo-ablation efficacy, especially in the mono-therapeutic model. To overcome those obstacles, we prepare an esterase-activated DM nano-prodrug, which is conjugated by diiodine-substituted fluorogenic malachite green derivative (MG-2I) and phototherapeutic agent DPP-OH via hydrolyzable ester linkage, having pH-responsiveness and genetically targetable activity for dual organelles-targeting to optimize photo-ablation efficacy. The DM nanoparticles (NPs) present improved pH-responsive photothermal/photodynamic property by the protonation of diethylaminophenyl units in acidic environment. More importantly, the MG-2I and DPP-OH moieties can be released from DM nano-prodrug through overexpressed esterase; then specifically target lysosomes and mitochondria in CT-26 Mito-FAP cells. Hence, near-infrared DM NPs can trigger parallel damage in dual-organelles with strong fluorescence and effective phototoxicity, thus inducing serious mitochondrial dysfunction and apoptotic death, showing excellent photo-ablation effect based on esterase-activated, pH-responsive, and genetically targetable activities.

Generation of vector beams based on diffraction characteristics of a linear polarization hologram in coaxial recording.

Polarization holography is an effective tool for realizing light field manipulation and can be utilized to generate vector beams. Based on the diffraction characteristics of a linear polarization hologram in coaxial recording, an approach for generating arbitrary vector beams is proposed. Unlike the previous methods for generating vector beams, in this work, it is independent of faithful reconstruction effect and the arbitrary linear polarization waves can be used as reading waves. The desired generalized vector beam polarization patterns can be adjusted by changing the polarized direction angle of the reading wave. Therefore, it is more flexible than the previously reported methods in generating vector beams. The experimental results are consistent with the theoretical prediction.

Polyethylene glycol with dual three-dimensional porous carbon nanotube/diamond: a high thermal conductivity of composite PCM.

Polyethylene glycol (PEG) is widely used as a phase change material (PCM) in thermal energy storage systems due to its high latent heat and chemical stability. However, practical application has been hindered by its low thermal conductivity and leakage issues. Therefore, developing shape-stable high thermal conductivity PCM is of great importance. In this study, new shape-stable composite PCM with high thermal conductivity and leak-prevention capabilities were designed. The porous carbon skeleton of diamond foam (DF) and dual-3D carbon nanotube-diamond foam (CDF) were prepared using the microwave plasma chemical vapor deposition method. The composite materials (DF/PEG and CDF/PEG) were produced by vacuum impregnation with PEG and skeletons. The results showed that CDF/PEG had the highest thermal conductivity, measuring 2.30 W·m-1·K-1, which is 707% higher than that of pure PEG. The employing of 3D networks of CNTs, which can improve the phonon mean free path in DF/PEG (1.79 W·m-1·K-1) while reducing phonon dispersion.The phonon vibration of dual-3D CDF plays an important role in heat transfer. PEG was physically absorbed and well-distributed in CDF, alleviating leakage of liquid PEG. The weight loss of CDF/PEG was only 25% at 70 °C for 120 s. Using CDF is an attractive and efficient strategy to increase the heat transfer of PEG and improve heat storage efficiency, alleviate the problem of poor shape-stability.

The benefits of using atypical presentations and rare diseases in problem-based learning in undergraduate medical education.

BACKGROUND: The nature of student learning in problem-based learning (PBL) largely depends on the quality of the case scenarios presented to them. The effect of case scenarios with higher challenge degree, especially common disease with atypical symptoms (CDAS)- and rare disease (RD)-based case scenarios, on undergraduate medical students remains unclear. This study compared the impact of all scenarios pertaining to common disease with typical symptoms (CDTS) case scenarios, CDTS interspersed with CDAS case scenarios, and CDTS interspersed with RD case scenarios on perceptions of undergraduate students studying organ/system integration curriculum via PBL. METHODS: After finishing four CDTS case scenarios, 294 third-year medical students were randomly allocated into three groups: CDTS, CDAS and RD, studying via CDTS, CDAS and RD case scenarios, respectively. A questionnaire with 15 items was conducted to evaluate the students' perceptions. The students' responses were scored using a 4-point rating scale. The data were analysed using the Kruskal-Wallis test. RESULTS: Among the three PBL conditions, the ones with a higher degree of challenge were rated higher by the students, which included the quality of the case scenarios and the overall performances of the students. The CDAS and RD cases were more effective in developing students' self-directed learning skills, stimulating them to acquire more knowledge required for future work. The satisfaction percentage of RD case scenario sessions was higher. CONCLUSIONS: Of all the three kinds of case scenarios, both CDTS interspersed with CDAS and RD case scenarios had more positive effects on the self-evaluated performance of students. Increasing the challenge and variety of case scenarios by the inclusion of CDAS and RD especially RD might be an effective stimulus in improving students' performance in PBL sessions.

An acceptability study of the introduction of total online or partial online PBL in a large classroom setting in biochemistry.

BACKGROUND: Traditional problem-based learning (PBL) relying on tutored learning in small groups is very resource-intensive. Little is known about the benefits of PBL in a large classroom setting. This paper introduced a PBL case into the traditional didactic biochemistry course and investigated the acceptability of total online or partial online PBL in a large classroom setting introduced during the coronavirus pandemic. METHODS: The students were allocated into either total online Group 1, partial online Group 2, or partial online and with poorer academic performance Group 3. A questionnaire comprising of 8 closed-ended questions and 2 open-ended questions and final exam performances were used to evaluate the acceptability of total online or partial online PBL in a large classroom setting. The 8 closed-ended questions were analysed by the Kruskal-Wallis test or chi-square tests. The word cloud analysis of the 2 open-ended questions were conducted by Wenjuanxing. Students' performances in the final examination were analysed by One-way Anova. RESULTS: Both total online and partial online PBL were rated highly by the students. Overall, there were no significant differences in the effectiveness evaluation of PBL between Group 2 and Group 3. There were no significant differences in final exam performances between Group 1 and Group 2. However, Group 1 rated the effectiveness of PBL much higher than Group 2 and 3. Word cloud analysis of the 2 open-ended questions showed students' positive perspectives of PBL. In biochemistry teaching, from the perspective of the students, the expected optimal number of useful PBL cases might be 2. CONCLUSIONS: Both total online and partial online PBL in a large classroom setting were widely accepted as a beneficial supplement to traditional biochemistry classes.

AccsHSP21.7 enhances the antioxidant capacity of Apis cerana cerana.

BACKGROUND: The widespread use of glyphosate has many adverse effects on Apis cerana cerana. Due to the incomplete understanding of the molecular mechanisms of glyphosate toxicity, there are no available methods for mitigating the threat of glyphosate to Apis cerana cerana. Small heat shock proteins (sHSPs) play an important role in resisting oxidative stress, but their mechanism of action in Apis cerana cerana remains unclear. RESULTS: In this experiment, we cloned and identified AccsHSP21.7. Studies have shown that AccsHSP21.7 contains binding motifs for various transcription factors related to oxidative stress. Abiotic stresses induced the expression of AccsHSP21.7. Bacteriostatic testing of a recombinant AccsHSP21.7 protein proved that Escherichia coli overexpressing AccsHSP21.7 showed increased resistance to oxidative stress. Knocking down the AccsHSP21.7 gene caused significant damage to midgut cells, which seriously disrupted the antioxidant system in Apis cerana cerana and greatly increased mortality under glyphosate stress. CONCLUSION: This study investigated the relationship between antioxidant regulation and the AccsHSP21.7 gene at the molecular level, and the results have guiding significance for the improvement of stress resistance in Apis cerana cerana. © 2023 Society of Chemical Industry.

Acetylshikonin induces autophagy-dependent apoptosis through the key LKB1-AMPK and PI3K/Akt-regulated mTOR signalling pathways in HL-60 cells.

Acetylshikonin (ASK) is a natural naphthoquinone derivative of traditional Chinese medicine Lithospermum erythrorhyzon. It has been reported that ASK has bactericidal, anti-inflammatory and antitumour effects. However, whether ASK induces apoptosis and autophagy in acute myeloid leukaemia (AML) cells and the underlying mechanism are still unclear. Here, we explored the roles of apoptosis and autophagy in ASK-induced cell death and the potential molecular mechanisms in human AML HL-60 cells. The results demonstrated that ASK remarkably inhibited the cell proliferation, viability and induced apoptosis in HL-60 cells through the mitochondrial pathway, and ASK promoted cell cycle arrest in the S-phase. In addition, the increased formation of autophagosomes, the turnover from light chain 3B (LC3B) I to LC3B II and decrease of P62 suggested the induction of autophagy by ASK. Furthermore, ASK significantly decreased PI3K, phospho-Akt and p-p70S6K expression, while enhanced phospho-AMP-activated protein kinase (AMPK) and phospho-liver kinase B1(LKB1) expression. The suppression of ASK-induced the conversion from LC3B I to LC3B II caused by the application of inhibitors of AMPK (compound C) demonstrated that ASK-induced autophagy depends on the LKB1/AMPK pathway. These data suggested that the autophagy induced by ASK were dependent on the activation of LKB1/AMPK signalling and suppression of PI3K/Akt/mTOR pathways. The cleavage of the apoptosis-related markers caspase-3 and caspase-9 and the activity of caspase-3 induced by ASK were markedly reduced by inhibitor of AMPK (compound C), an autophagy inhibitor 3-methyladenine (3-MA) and another autophagy inhibitor chloroquine (CQ). Taken together, our data reveal that ASK-induced HL-60 cell apoptosis is dependent on the activation of autophagy via the LKB1/AMPK and PI3K/Akt-regulated mTOR signalling pathways.

BAFinder: A Software for Unknown Bile Acid Identification Using Accurate Mass LC-MS/MS in Positive and Negative Modes.

Most LC-MS based bile acid analyses target common bile acids. The identification of unknown bile acids remains challenging in untargeted experiments. Here, a software named BAFinder was developed to improve the identification of unknown bile acids from accurate mass LC-MS/MS data in both the positive and negative ESI modes. A wide variety of bile acid structures were covered in BAFinder, including oxidized bile acids and sugar conjugates that were often ignored. The annotation of unknown bile acids was based on a thorough investigation of MS/MS fragmentation patterns of 84 bile acid reference standards in both modes. Specifically, BAFinder took the peak alignment result and MS/MS spectra, grouped candidate features in positive and negative modes, searched their representative MS/MS spectra against a MS/MS library, and used characteristic product ions and neutral losses to annotate bile acids not covered in the library. Finally, the number of hydroxyl groups and double bonds, conjugation, and isomer information of bile acids were reported with four different levels of annotation confidence. The use of BAFinder was demonstrated through successful application to the analysis of human plasma and urine samples, in which a total of 112 and 244 bile acids were annotated and 75 and 111 of them were confirmed with standards or synthesized compounds, respectively. The software is freely available at https://bafinder.github.io/.

Simple method for generating special beams using polarization holography.

Vector vortex beams are a kind of special beam that simultaneously carry spin and orbital angular momentum. The generation of vector vortex beams usually requires a complex and expensive optical system, which becomes a bottleneck hindering its further application. Thus, a compact, low-cost and efficient special beam generation system is demanded. In this paper, a method that can produce vector vortex beams distributed anywhere in the equator of hybrid-order Poincaré Spheres based on polarization holography is proposed. Via changing some parameters of the device, this method can also produce the scalar vortex beams distributed at any position of the basic Poincaré Sphere and the vector beams distributed at the equator of the higher-order Poincaré Spheres. The work shows that polarization holography has the potential ability to regulate the spin and orbital angular momentum simultaneously, opening a new window for future research and applications of angular momentum space orientation.

Simultaneously characterized Stokes parameters of a lightwave utilizing the tensor polarization holography theory.

Polarization is a natural property of a lightwave and makes a significant contribution to various scientific and technological applications, due to the different states of polarization (SoP) of a lightwave that may manifest distinct behaviors. Hence, it is important to determine the SoP of the lightwave. Generally, the SoP of a lightwave can be recognized by the Stokes parameters. In this paper, we proposed a novel method to simultaneously characterize the Stokes parameters of a lightwave, by employing the tensor polarization holography theory. This is done through merely a piece of polarization-sensitive material. Compared with the traditional method, this method requires only one measurement to obtain all the Stokes parameters, without using additional polarizing elements. The experimental result shows excellent agreement with the theoretical one, which confirmed the reliability and accuracy of the proposed method. We believe that this work may broaden the application field of polarization holography.

Circular polarization detector based on polarization holography.

We propose and experimentally demonstrate the generation of a circular polarization detector based on planar polarization holography. The detector is designed by constructing the interference field according to the null reconstruction effect. We create multiplexed holograms, which feature the combination of two sets of hologram patterns and operate with opposite circular polarization beams. In a few seconds, the exposure operation allows the polarization multiplexed hologram element to be generated, with functionality equivalent to a chiral hologram. We have theoretically analyzed the feasibility of our scheme and experimentally demonstrated that the right- and left-handed circularly polarized beam can be distinguished directly depending on the different output signals. This work provides a time-saving and cost-effective alternative approach for generating a circular polarization detector and opens avenues for future applications in polarization detection.

Selective synergistic anticancer effects of cisplatin and oridonin against human p53-mutant esophageal squamous carcinoma cells.

Oridonin (ORI) is known to pose anticancer activity against cancer, which could induce the therapeutic impact of chemotherapy drugs. However, such simple combinations have numerous side effects such as higher toxicity to normal cells and tissues. To enhance the therapeutic effects with minimal side effects, here we used ORI in combination with cisplitin (CIS) against different esophageal squamous cell carcinoma (ESCC) cell lines in vitro, to investigate the synergistic anticancer effects of the two drugs against ESCC. Calcusyn Graphing Software was used to assess the synergistic effect. Apoptosis, wound healing and cell invasion assay were conducted to further confirm the synergistic effects of ORI and CIS. Intracellular glutathione (GSH) and reactive oxygen species assay, immunofluorescence staining and western blot were used to verify the mechanism of synergistic cytotoxicity. ORI and CIS pose selective synergistic effects on ESCC cells with p53 mutations. Moreover, we found that the synergistic effects of these drugs are mediated by GSH/ROS systems, such that intracellular GSH production was inhibited, whereas the ROS generation was induced following ORI and CIS application. In addition, we noted that DNA damage was induced as in response to ORI and CIS treatment. Overall, these results suggest that ORI can synergistically enhance the effect of CIS, and GSH deficiency and p53 mutation, might be biomarkers for the combinational usage of ORI and CIS.

Regulation of Adropin by Sitagliptin monotherapy in participants with newly diagnosed type 2 Diabetes.

BACKGROUND: Adropin is a potent metabolic regulator of insulin sensitivity and glycolipid metabolism. The present study investigated the effects of sitagliptin on adropin and metabolic parameters in participants with newly diagnosed type 2 diabetes (T2D). METHODS: Thirty-five participants newly-diagnosed with T2D were prescribed sitagliptin 100 mg once daily for 17 weeks. Twenty-eight age-, sex-, and BMI-matched healthy subjects were included as the control group. Adropin and clinical parameters were assessed at baseline and after treatment. RESULTS: At baseline, serum adropin levels were lower in T2D participants than in the healthy individuals (3.12 ± 0.73 vs. 5.90 ± 1.22 ng/ml, P <  0.01). Serum adropin levels were significantly higher in T2D patients after sitagliptin treatment (4.97 ± 1.01 vs. 3.12 ± 0.73 ng/ml, P <  0.01). The changes in serum adropin levels after sitagliptin treatment were associated with the improvements of fasting blood glucose (FBG) (ß = - 0.71, P <  0.01), glycosylated hemoglobin (HbA1c) (ß = - 0.44, P <  0.01) and homeostatic model assessment of ß-cell function (HOMA-ß) (ß = 9.02, P <  0.01). CONCLUSIONS: Sitagliptin treatment could significantly increase serum adropin levels in participants with newly diagnosed T2D. The increase in serum adropin levels could be associated with the amelioration of glucose metabolism, which might be involved in beneficial glucose-lowering mechanisms of sitagliptin. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04495881 . Retrospectively registered on 03/08/2020.

Phenanthraquinone-Doped Polymethyl Methacrylate Photopolymer for Holographic Recording.

Phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymers are considered to be the most promising holographic storage media due to their unique properties, such as high stability, a simple preparation process, low price, and volumetric shrinkage. This paper reviews the development process of PQ/PMMA photopolymers from inception to the present, summarizes the process, and looks at the development potential of PQ/PMMA in practical applications.

Generation of circular polarization with an arbitrarily polarized reading wave.

Polarization holography has attracted considerable attention in recent years, due to its capability of recording the polarization information in polarization-sensitive material. Particularly, the faithful reconstruction (FR) can retrieve the polarization information of the recorded signal. To date, studies referring to these topics mainly concentrate on the interference between the same type of polarization such as linearly, circularly, and elliptically polarized light. In addition, most of the reading wave is strictly limited to some specified polarization state to achieve the FR. Here, we apply the linearly polarized light as the reference wave to record the circularly polarized light, and then the circular polarization state would be faithfully reconstructed by the arbitrarily polarized reading wave. We theoretically analyze its polarization characteristic based on the tensor theory and experimentally verified the analytical results. This result further extending the FR in polarization holography, and provides a practicable way to generate circular polarization which is easily fabricated. Moreover, the work would lay a favorable theoretical foundation for the future preparation of circular polarization generator and discloses a new insight in polarization manipulation for tailoring the optical field.

Exposure response coefficient of polarization-sensitive media using tensor theory of polarization holography.

We report a method for measuring the exposure response coefficient of polarization-sensitive media using the tensor theory of polarization holography. According to the theory of polarization holography based on the tensor method, the exposure response coefficient of polarization-sensitive media is not only determined by the materials but also affected by the exposure energy. The exposure response coefficient changing with the exposure energy is the key factor in polarization holography for controlling the polarization state of the reconstructed wave. We summarize the change of the polarization state of the reconstructed wave with the exposure energy under different recording conditions and obtain the initial value (about 8.4) of the exposure response coefficient of the polarization-sensitive media. Finally, the null reconstruction of linear polarization wave is realized by using this initial value.

Generation of a vector light field based on polarization holography.

We propose a simple and effective method for generating a vector light field based on the faithful reconstruction (FR) effect of polarization holography, where the arbitrary linear polarization waves can be faithfully reconstructed by the polarization-sensitive recording media. The scheme incorporates the tunable and switchable dynamics exposure system to manufacture vector beams. By regulating the velocity and the initial polarization through the angle-aperture and the half-wave plate in the dynamics exposure system, the generated optical element can convert a linear polarization wave into a vector beam. We have analyzed the feasibility in theory and demonstrated the generation of the vector beams experimentally which shows good agreement with the theoretical simulations.

Frequency expanded non-interferometric phase retrieval for holographic data storage.

A novel frequency expanded non-interferometric phase retrieval method for holographic data storage is proposed. The limitation of twice Nyquist frequency for phase retrieval with high fidelity is broken through. Only 1 times Nyquist size frequency of the hologram is recorded, reconstructed and detected in our method which is the smallest range for complex multi-level phase retrieval in the current holographic data storage report. Required high-order frequencies for quick phase retrieval are generated artificially by expanding 1 times Nyquist frequency to high-order frequencies with utilizations of frequency periodicity. Therefore, our proposed method can increase storage density due to reducing the recording consumption of media and decreasing the recording area by 4 times compared with twice Nyquist frequency recording.

Collinear non-interferometric phase retrieval for holographic data storage.

A collinear non-interferometric phase retrieval method for holographic data storage is proposed. The code rate of the collinear system can be increased by 2 times due to transferring the 50% embedded data from a signal beam to a reference beam. Because the reference beam should be always known both in the recording process and reading process, there is no extra material cost for saving the embedded data. Therefore, the storage density of collinear system is increased by about 2 times compared with previous off-axis non-interferometric phase retrieval systems. Besides, we can enhance the algorithm constraint to shorten iteration numbers by increasing the amplitude weight of the reference beam. In the experiment, we shortened the iteration number and the BER by about 3 times. We also find that the reference number can be reduced by using the collinear way and increasing the amplitude weight of reference. This law allows us to give more code positions to signal so that the data amount in one data page can be increased.

Projecting China's future water footprint under the shared socio-economic pathways.

Increasing water scarcity in China is further exacerbated by the rapid socio-economic development and uneven spatial distribution of water resources. Current studies on water footprint have mainly focused on historical accounting and trend analysis at the provincial scale. However, a comprehensive exploration of future water footprint would be vital to a better understanding of future water shortage challenges, and more importantly, would allow the mitigation of water scarcity and inequal water distribution. In this paper, we present an approach to project the future water footprint of China at a fine resolution (0.125 arc-degree) under the shared socio-economic pathway (SSP) scenario framework, which described five future alternative socio-economic development pathways over the 21st century. We first simulated the future spatial patterns of built-up land using the Future Land Use Simulation (FLUS) model and derived the future population growth and urbanization rate from the population projection provided by the National Center for Atmospheric Research (NCAR). Then future water footprint was projected according a log-transformed linear regression calibrated with historical data during 2007-2012. We found that the total volume of China's water footprint will increase significantly in the future under the SSP1, SSP4 and SSP5 scenarios, reaching up to nearly 400 billion m3 in 2050, equivalent to almost 40% increase compared to that in 2010. The spatial patterns of future water footprint show dramatic increase (up to 100-130%) in the eastern provinces (Shandong, Henan, and Hebei), and slight decrease were found in the western provinces (Xinjiang, Ningxia, and Qinghai). In addition, the future water footprints were found to share very similar spatial patterns at local pixel scale among different SSP scenarios in three of the largest metropolitan areas of China (Beijing-Hebei-Tianjin, Yangtze River Delta, and Pearl River Delta). These findings provide extensive knowledge of the future water footprint and suggest a more severe water scarcity in the future from a consumption-oriented perspective. More effective water management policies are urgently needed to mitigate future water resource scarcity and inequality.