Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer.

Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.

Effect of the configuration mixing on the polarization and angular distribution of x-ray line emissions following electron-impact excitation of Ne-like ions.

We present a systematic theoretical study on the angular distribution and linear polarization of x-ray line emissions of neon-like ions following the electron-impact excitation from the ground state to the excited levels [(2p5)1/23d3/2]J=1, [(2p5)3/23d5/2]J=1, [(2p5)3/23d3/2]J=1, and [(2p5)1/23s]J=1. The cross sections are calculated by using the flexible atomic code under configuration-interaction plus many-body perturbation theory method. The angular distribution and linear polarization are obtained based on density matrix theory. Emphasis has been placed on the effect of the configuration mixing on the angular distribution and polarization. It has been proved that the strong mixing of configuration [(2p5)3/23d3/2]J=1 with configuration [(2p5)1/23s]J=1 can result in the abrupt change of Z-dependence of angular distribution and polarization. It indicates that angular distribution and polarization can be expected to serve as a tool for investigation of configuration mixing effect.

Highly efficient recovery of Zn (II) from zinc-containing wastewater by tourmaline tailings geopolymers to in-situ construct nanoscale ZnS for the photodegradation of tetracycline hydrochloride.

While treating zinc-containing wastewater, recovering zinc for reuse as a secondary resource has significant environmental and economic benefits. Herein, based on the alkali-activated tourmaline tailings geopolymers (TTG) after adsorption of zinc ions (Zn (II)), a series of new composites with in-situ construction ZnS nanoparticles on TTG (ZnS/TTG) were synthesized, and used as photocatalysts for the photodegradation of tetracycline hydrochloride (TCH) in solution. Specifically, ZnS nanoparticles were uniformly and stably distributed in the layered structure of TTG, interweaving with each other to generate an interfacial electric field, which could induce more photocarrier generation. Meanwhile, TTG acted as an electron acceptor to accelerate the electron transfer at the interface, thus enhancing the photodegradation activity for TCH. The active radical quenching experiments combined with the ESR indicated that the active species produced during the photocatalytic degradation of TCH by ZnS/TTG composites were •O2- and photogenerated h+. When the initial concentration of Zn (II) was 60 mg/L, the synthesized 60-ZnS/TTG composites (0.5 g/L) reached 91.53% degradation efficiency of TCH (10 mg/L) at pH = 6. Furthermore, the possible pathways and mechanism of 60-ZnS/TTG composites photodegraded TCH were revealed with the aid of degraded intermediates. This report not only proposed valuable references for reusing heavy metal ions and removing TCH from wastewater, but also provided promising ideas for realizing the conversion of used adsorbents into high-efficiency photocatalysts.

Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women.

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Therapeutic efficacy of drilling drainage combined with intraoperative middle meningeal artery occlusion in the management of chronic subdural hematoma: a clinical study.

BACKGROUND: The bone holes in the skull during surgical drainage were accurately located at the site of the MMA. The MMA was severed, and the hematoma was removed intraoperatively; furthermore, surgical drainage removed the pathogenic factors of CSDH. This study aimed to describe and compare the results of the new treatment with those of traditional surgical drainage, and to investigate the relevance of this approach. METHODS: From December 2021 to June 2023, 72 patients were randomly assigned to the observation group and the control group. The control group was treated with traditional surgical drainage, while the observation group was treated with DSA imaging to accurately locate the bone holes drilled in the skull on the MMA trunk before traditional surgical drainage. The MMA trunk was severed during the surgical drainage of the hematoma. The recurrence rate, time of indwelling drainage tube, complications, mRS, and other indicators of the two groups were compared, and the changes of cytokine components and imaging characteristics of the patients were collected and analyzed. RESULTS: Overall, 27 patients with 29-side hematoma in the observation group and 45 patients with 48-side hematoma in the control group were included in the study. The recurrence rate was 0/29 in the observation group and 4/48 in the control group, indicating that the recurrence rate in the observation group was lower than in the control group (P = .048). The mean indwelling time of the drainage tube in the observation group was 2.04 ± 0.61 days, and that in the control group was 2.48 ± 0.61 days. The indwelling time of the drainage tube in the observation group was shorter than in the control group (P = .003). No surgical complications were observed in the observation group or the control group. The differences in mRS scores before and after operation between the observation group and the control group were statistically significant (P < .001). The concentrations of cytokine IL6/IL8/IL10/VEGF in the hematoma fluid of the observation and control groups were significantly higher than those in venous blood (P < .001). After intraoperative irrigation and drainage, the concentrations of cytokines (IL6/IL8/IL10/VEGF) in the subdural hematoma fluid were significantly lower than they were preoperatively. In the observation group, the number of MMA on the hematoma side (11/29) before STA development was higher than that on the non-hematoma side (1/25), and the difference was statistically significant (P = .003). CONCLUSION: In patients with CSDH, accurately locating the MMA during surgical trepanation and drainage, severing the MMA during drainage, and properly draining the hematoma, can reduce the recurrence rate and retention time of drainage tubes, thereby significantly improving the postoperative mRS Score without increasing surgical complications.

Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.

Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.

Exogenous hydrogen sulfide prevents necroptosis by inhibiting p38MAPK pathway activation in JEG-3 trophoblast cells: A role in preeclampsia.

Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. DESIGN: This is an in vitro experimental study. PARTICIPANTS: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. METHODS: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). RESULTS: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-ß-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. LIMITATIONS: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. CONCLUSIONS: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.

Cadherin Is a Binding Protein but Not a Functional Receptor of Bacillus thuringiensis Cry2Ab in Helicoverpa armigera.

Midgut receptors play a critical role in the specificity of Cry toxins for individual insect species. Cadherin proteins are essential putative receptors of Cry1A toxins in lepidopteran larvae. Cry2A family members share common binding sites in Helicoverpa armigera, and one of them, Cry2Aa, has been widely reported to interact with midgut cadherin. Here, we studied the binding interaction and functional role of H. armigera cadherin in the mechanism of Cry2Ab toxicity. A region spanning from cadherin repeat 6 (CR6) to the membrane-proximal region (MPR) of cadherin protein was produced as six overlapping peptides to identify the specific binding regions of Cry2Ab. Binding assays showed that Cry2Ab binds nonspecifically to peptides containing CR7 and CR11 regions in a denatured state but binds specifically only to CR7-containing peptides in the native state. The peptides CR6-11 and CR6-8 were transiently expressed in Sf9 cells to assess the functional role of cadherin. Cytotoxicity assays showed that Cry2Ab is not toxic to the cells expressing any of the cadherin peptides. However, ABCA2-expressing cells showed high sensitivity to Cry2Ab toxin. Neither increased nor decreased sensitivity to Cry2Ab was observed when the peptide CR6-11 was coexpressed with the ABCA2 gene in Sf9 cells. Instead, treating ABCA2-expressing cells with a mixture of Cry2Ab and CR6-8 peptides resulted in significantly reduced cell death compared with treatment with Cry2Ab alone. Moreover, silencing of the cadherin gene in H. armigera larvae showed no significant effect on Cry2Ab toxicity, in contrast to the reduced mortality in ABCA2-silenced larvae. IMPORTANCE To improve the efficiency of production of a single toxin in crops and to delay the evolution of insect resistance to the toxin, the second generation of Bt cotton, expressing Cry1Ac and Cry2Ab, was introduced. Understanding the mode action of the Cry proteins in the insect midgut and the mechanisms insects use to overcome these toxins plays a crucial role in developing measures to counter them. Extensive studies have been conducted on the receptors of Cry1A toxins, but relatively little has been done about those of Cry2Ab. By showing the nonfunctional binding of cadherin protein with Cry2Ab, we have furthered the understanding of Cry2Ab receptors.

Freestanding narrowband terahertz filters based on aluminum foil.

Terahertz (THz) filters with high transmission coefficient (T) in the passband and frequency selectivity are critical in numerous applications such as astronomical detection and next-generation wireless communication. Freestanding bandpass filters eliminate the Fabry-Pérot effect of substrate, thus providing a promising choice for cascaded THz metasurfaces. However, the freestanding bandpass filters (BPFs) using the traditional fabrication process are costly and fragile. Here, we demonstrate a methodology to fabricate THz BPFs using aluminum (Al) foils. We designed a series of filters with center frequencies below 2 THz and manufacture them on 2-inch Al foils with various thicknesses. By optimizing the geometry, T of the filter at the center frequency is over 92%, and the relative full-width half maxima (FWHM) is as narrow as 9%. The responses of BPFs show that "cross-shaped" structures are insensitive to the polarization direction. The simple and low-cost fabrication process of the freestanding BPFs promise their widespread applications in THz systems.

Effects of the online and offline hybrid continuous group care on maternal and infant health: a randomized controlled trial.

BACKGROUND: The group care is a well-established maternal care model that has been widely used in many developed countries, but in China, it is confined to prenatal care services. In addition, affected by traditional birth culture, Chinese women tend to focus more on their fetuses and newborns but lack attention to their own intrapartum and postpartum care. The aim of this study was to construct and implement a prenatal, intrapartum, and the postpartum continuous group care model that combines online and offline service in Hainan Province, China, and to evaluate the effect on maternal women and newborns. METHODS: This study was a randomized controlled trial involving 144 pregnant women in a first-class tertiary general hospital in Hainan Province, China. Women were divided into an intervention group and a control group using the random number table, with 72 women in each group. The control group received routine maternal care services, and the intervention group received the continuous group care based on the routine maternal care services. Count data such as rate of cesarean section and incidence rate of fetal macrosomia were analyzed with the chi-square test or Fisher's exact test, and the General Self-efficacy Scale scores were analyzed by repeated measures ANOVA. P < 0.05 was considered statistically significant, with two-sided probability values. RESULTS: Compared with the control group, the rate of excessive prenatal weight gain, cesarean section, and 42-day postpartum depression were significantly lower in the intervention group (P < 0.05), and higher General Self-efficacy Scale scores (in the expectant period and 42 days postpartum) and exclusive breastfeeding rate (42 days postpartum) (P < 0.05). The incidence of fetal macrosomia was significantly lower in the intervention group (P < 0.05). But there was no significant difference in birth weight, preterm birth, the incidence of low-birth-weight infants and 1-min Apgar score (P > 0.05). CONCLUSION: The continuous group care with online and offline service can effectively control the gestational weight gain, reduce the rate of cesarean section, macrosomia, and postpartum depression. It can improve the self-efficacy of women and the rate of exclusive breastfeeding effectively. TRIAL REGISTRATION: Chinese Clinical Trial Regestry (ChiCTR2200065765, 04/11/2022, Retrospectively registered).

A nomogram prediction of citrate reaction during mononuclear cell collection in solid tumor patients.

PURPOSE: Citrate reaction is one of the main adverse events in peripheral blood mononuclear cell (MNC) collection. The aim of this study was to elucidate the risk factors for citrate reaction in patients with advanced solid tumor collection and to construct a nomogram to predict the risk. METHODS: One hundred forty-eight patients with advanced solid tumor who underwent peripheral blood MNC collection in our hospital between January 2021 to December 2021 were selected. The general data, creatinine level before collection, Ca2+ concentration before collection, absolute value of monocyte lymphocytes before collection, circulating blood volume, anticoagulant dosage, and blood collection duration were included in Logistic regression analysis to identify the risk factors of citrate reaction. According to the results of the multivariate logistic model, nomogram was established and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model. RESULTS: Among the 148 solid tumor patients, 35 patients (23.6%) of the 148 patients developed citrate reaction. Multivariate analysis showed that the risk factors for citrate reaction in the process of collection included sex (odds ratio [OR] = 6.718; 95% confidence interval [95% CI]: 2.191-20.594, P = .001), age (OR = 0.957; 95% CI: 0.921-0.996, P = .03), and processed circulating blood volume (OR = 1.001; 95% CI: 1.000-1.002, P = .01). Logistic regression can analyze independent risk factors and establish risk prediction model. The predictive performance of the model is good, and the area under ROC curve is 0.799. CONCLUSIONS: The MNC collection process is safe. The incidence of citrate reaction in the collection of peripheral blood MNCs from patients with advanced solid tumor is related to the age, gender, and processed circulating blood volume of patients. The nomogram can be used to assess a patient's risk of citrate reaction.

Simple terahertz metasurface with broadband and efficient functionality.

Pancharatnam-Berry (PB) metasurfaces have demonstrated mighty capability to manipulate electromagnetic (EM) waves, and exhibited potential applications for devices with broadband and efficient functionality. However, it remains a challenge to simultaneously achieve broadband and efficient wavefront manipulation for terahertz (THz) components with simple profiles. Herein, we introduce a simple ultra-thin PB metasurface with superior properties in the THz region. The structure is composed of a simple metallic C-Shaped Split Ring Resonator (CSRR) patterned on a flexible polyimide support layer. It is verified that the circular transmission efficiency is close to the theoretical limit of the single-layer metasurface in the range of 0.6 - 1.2 THz. Furthermore, we design metasurfaces based on the PB meta-atoms with spatially rotated orientation to achieve beam steering and superposition of vortex waves. The results are basically in line with expectations, validating the good performances of our proposal. This simple and easily deployable metasurface will give rise to more possibilities for the design of THz functional devices.

Anisotropic coding metasurfaces and their active manipulation based on vanadium dioxide for multifunctional applications in the terahertz region.

Various kinds of metasurfaces have been proposed because they can be tailored to achieve the desired modulations on electromagnetic wave that do not occur in nature. Compared to conventional metamaterials, coding metasurfaces integrated with information science theory possess numerous distinctive advantages - simple design, time-saving and compatibility with digital devices. Here we propose terahertz multifunctional anisotropic reflective metasurfaces with a metal-insulator-metal cavity structure whose top constructional layer consists of a pair of gold arc-rings and a gold cut-wire located between them. Two different functions of narrow-band absorption and broadband polarization conversion are realized based on different coding matrices using the binary codes '0' and '1'. Furthermore, we integrate a specific coding metasurface with vanadium dioxide (VO2) to realize a temperature-controlled active metasurface. Through the temperature change, dynamic functionalities switching between a narrow-band polarization converter with a polarization conversion ratio over 94% and an efficient low-pass filter are achieved under the phase transition of VO2, and the active metasurface is polarization independent. The proposed coding metasurfaces are verified numerically and experimentally, and have promising applications in terahertz modulation and functional devices.

A novel electrochemical sensor based on AuPd/UiO-66-NH2/GN composites for sensitive dopamine detection.

Metal-organic frameworks (MOFs) have emerged as interesting nanomaterials owing to their large surface area, high porosity, tunable pore architecture and easy functionalization. However, an inferior electrical conductivity hinders their application in electrochemical sensing. In this paper, gold-palladium alloy/UiO-66-NH2/graphene (AuPd/UiO-66-NH2/GN) composites were synthesized by loading alloys on the surfaces of MOFs and then attaching them to the graphene surface. The addition of metal nanoparticles and graphene enhanced the electron transfer ability of MOFs. Then, composites were used to modify a glassy carbon electrode (GCE) to construct a sensitive dopamine (DA) electrochemical sensor. The developed sensor manifested two linear relationships in lower concentration ranges and in higher concentration ranges with a 0.21 × 10-6 mol L-1 low detection limit (3σ/k) under optimal conditions. The results certified that the constructed sensor had high selectivity, excellent reproducibility and good stability, and had been used successfully for DA detection in actual human serum samples.

A selective electrochemical chiral interface based on a carboxymethyl-ß-cyclodextrin/Pd@Au nanoparticles/3D reduced graphene oxide nanocomposite for tyrosine enantiomer recognition.

Palladium@gold nanoparticle modified three-dimensional-reduced graphene oxide (3D-rGO/Pd@Au) was coupled with carboxymethyl-ß-cyclodextrin to form a novel nanocomposite (3D-rGO/Pd@Au/CM-ß-CD). The 3D-rGO/Pd@Au/CM-ß-CD served as a chiral sensing interface for the electrochemical enantiorecognition of tyrosine (Tyr) via a differential pulse voltammetry (DPV) approach. The 3D-rGO/Pd@Au demonstrates good electrical conductivity and efficient catalytic activity as an electrochemical indicator. Simultaneously, the CM-ß-CD displays a supramolecular chiral selectivity to reveal a higher binding affinity to the target L-tyrosine (L-Tyr) than to D-tyrosine (D-Tyr). Under the optimized determining conditions, the oxidation peak current ratio of L-Tyr to D-Tyr (IL/ID) was 2.12, meanwhile, the peak currents of the two isomers were linearly proportional to the concentration over the range of 0.8-130 µM with LODs of 52 nM and 96 nM for L- and D-Tyr (S/N = 3), respectively. This approach exhibits distinguished sensitivity, excellent selectivity and good reproducibility, as well as great stability, which can accurately determine the relative content of L- or D-Tyr enantiomers in a racemic solution.

High level of homocysteine is associated with pre-eclampsia risk in pregnant woman: a meta-analysis.

OBJECTIVE: We aimed to investigate the correlation between blood homocysteine (Hcy) levels and pre-eclampsia (PE) risk in pregnant women. METHODS: Related articles were searched using PubMed, Embase, and Web of Science databases. Methodological quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). Cochran's Q and I2 tests were used to evaluate heterogeneity. Egger's test was used to evaluate publication bias. A sensitivity analysis was performed to test stability of the results using a one-by-one elimination method. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess certainty of evidence. RESULTS: Nine studies (4384 PE and 26021 non-PE patients) were included in the meta-analysis. The methodology of them was of good quality, with NOS scores of 5-8. However, there was a significant heterogeneity among included studies. Therefore, the random effect model was generated and combined results suggested a significant association between increased level of Hcy in pregnant women and PE risk. Although a significant publication bias was found in the current study with a P value of 0.006 in the Egger test, sensitivity analysis showed that the combined results were stable and did not vary significantly from any single study. However, the GRADE evidence quality was very low, which may lower the recommendation of pooled results. CONCLUSIONS: Increased levels of Hcy in maternal blood were significantly associated with the risk of PE, but low certainty of evidence need to be improved by more high-quality studies.

Up-regulated serpin gene involved in Cry1Ac resistance in Helicoverpa armigera.

Insect resistance to Bacillus thuringiensis (Bt) is a critical limiting factor for applying the Bt crops. Some studies indicated that decreased protoxin activation because of lower enzymatic activities of trypsin and chymotrypsin and increased expression of serpin might involve in Bt resistance. Our previous study identified an endogenous serpin could inhibit the midgut proteases to activate Cry1Ac and reduce the insecticide activity to Helicoverpa armigera. We hypothesis that up-regulated serpin involve in resistance via inhibiting enzymatic activities of trypsin and chymotrypsin to decrease protoxin activation. Herein, we found the serpin-e gene relative expression in midgut was significantly higher in the LF30 resistant strain than that in the susceptible strain during all developmental stages. Importantly, RNAi-mediated silencing of serpin-e gene expression caused 4.46-fold mortality changes in LF30 strain, but the trypsin and chymotrypsin proteases activities were only changed 0.79-fold and 2.22-fold. In addition, although proteases activities were significantly lower in LF30 strain than that in the susceptible strain, the resistance ratios of LF30 to Cry1Ac protoxin and to activated Cry1Ac toxin were no difference. The results indicated serpins caused insect resistance to Cry1Ac protoxins partly through inhibiting the trypsin and chymotrypsin proteases activities, but it also existed other mechanisms in LF30.

The augment of regulatory T cells undermines the efficacy of anti-PD-L1 treatment in cervical cancer.

BACKGROUND: Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment. RESULTS: We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion. CONCLUSIONS: Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.

Lipid Droplet-Specific Fluorescent Probe for In Vivo Visualization of Polarity in Fatty Liver, Inflammation, and Cancer Models.

Elucidating the intrinsic relationship between diseases and lipid droplet (LD) polarity remains a great challenge owing to the lack of the research on multiple disease models. Until now, the visualization of abnormal LD polarity in models of inflammation and clinical cancer patient samples has not been achieved. To meet the urgent challenge, we facilely synthesized a robust LD-specific and polarity-sensitive fluorescent probe (LD-TTP), which consists of a triphenylamine segment as an electron-donor group (D) and a pyridinium as an electron-acceptor moiety (A), forming a typical D-π-A molecular configuration. Owing to the unique intramolecular charge transfer effect, LD-TTP exhibits high sensitivity to polarity change in the linear range from Δf = 0.258 to 0.312, with over 278-fold fluorescence enhancement. Moreover, we revealed that LD-TTP possessed satisfactory ability for sensitively monitoring LD-polarity changes in living cells. Using LD-TTP, we first demonstrated the detection of LD-polarity changes in fatty liver tissues and inflammatory living mice via confocal laser scanning fluorescence imaging. Surprisingly, the visualization of LD polarity has been achieved not only at the cellular levels and living organs but also in surgical specimens from cancer patients, thus holding great potential in the clinical diagnosis of human cancer. All these features render LD-TTP an effective tool for medical diagnosis of LD polarity-related diseases.

Flexible bilayer terahertz metasurface for the manipulation of orbital angular momentum states.

Metasurfaces employed for generating orbital angular momentum (OAM) beams have drawn tremendous interest since they can offer extensive applications ranging from quantum optics to information processing over the subwavelength scale. In this study, a flexible bilayer metasurface is proposed and experimentally verified in the terahertz (THz) region. Based on Pancharatnam-Berry (P-B) phase, the proposed meta-atom satisfies perfect polarization-flipping at the design frequency and is implemented for the generation of vortex beams under circularly polarized (CP) illumination. Two metasurfaces are designed, fabricated and experimentally characterized with a THz spectral imaging system for linearly polarized (LP) illumination. The transmitted field intensity distribution of y component is petal-shaped of gradually varied pieces with the frequency due to the complementary symmetric structure, indicating OAM state transition between a single vortex beam and superposition of two vortex beams. The measured spectral imaging distributions of amplitude and phase show good agreement with the simulation results. Such designs open a pathway for modulation of THz OAM states and bring more possibilities for flexible metasurfaces in a THz application.