NAT10-mediated N4-acetylcytidine mRNA modification regulates self-renewal in human embryonic stem cells.

NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. However, its role in mammalian development remains unclear. Here, we found that NAT10 expression positively correlates with pluripotency in vivo and in vitro. High throughput ac4C-targeted RNA immunoprecipitation sequencing (ac4C-RIP-seq), NaCNBH3-based chemical ac4C sequencing (ac4C-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays revealed noticeable ac4C modifications in transcriptome of hESCs, among which transcripts encoding core pluripotency transcription factors are favorable targets of ac4C modification. Further validation assays demonstrate that genetic inactivation of NAT10, the ac4C writer enzyme, led to ac4C level decrease on target genes, promoted the core pluripotency regulator OCT4 (POU5F1) transcript decay, and finally impaired self-renewal and promoted early differentiation in hESCs. Together, our work presented here elucidates a previously unrecognized interconnectivity between the core pluripotent transcriptional network for the maintenance of human ESC self-renewal and NAT10-catalyzed ac4C RNA epigenetic modification.

Selection strategy of second-line biologic therapies in adult patients with ulcerative colitis following prior biologic treatment failure: Systematic review and meta-analysis.

BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Defect-Rich, Highly Porous PtAg Nanoflowers with Superior Anti-Poisoning Ability for Efficient Methanol Oxidation Reaction.

The design of efficient and sustainable Pt-based catalysts is the key to the development of direct methanol fuel cells. However, most Pt-based catalysts still exhibit disadvantages including unsatisfied catalytic activity and serious CO poisoning in the methanol oxidation reaction (MOR). Herein, highly porous PtAg nanoflowers (NFs) with rich defects are synthesized by using liquid reduction combining chemical etching. It is demonstrated that the proportion of precursors determines the inhomogeneity of alloy elements, and the strong corrosiveness of nitric acid to silver leads to the eventual porous flower-like structure. Impressively, the optimal etched Pt1 Ag2 NFs have the mixed defects of surface steps, dislocations, and bulk holes, and their mass activity (1136 mA mgPt-1 ) is 2.6 times higher than that of commercial Pt/C catalysts, while the ratio of forward and backward peak current density (If /Ib ) can reach 3.2, exhibiting an excellent anti-poisoning ability. Density functional theory calculations further verify their high anti-poison properties from both an adsorption and an oxidation perspective of CO intermediate. The introduction of Ag makes it easier for CO to be oxidized and removed. This study provides a facile approach to prepare rich defects and porous alloy with excellent MOR performance and superior anti-poisoning ability.

PtCuRu Nanoflowers with Ru-Rich Edge for Efficient Fuel-Cell Electrocatalysis.

Enhancing the catalytic activity of Pt-based alloy by a rational structural design is the key to addressing the sluggish kinetics of direct alcohol fuel cells. Herein, a facile one-pot method is reported to synthesize PtCuRu nanoflowers (NFs). The synergetic effect among Pt, Cu, and Ru can lower the d-band center of Pt, regulate the morphology, generate Ru-rich edge, and allow the exposure of more high index facets. The optimized Pt0.68 Cu0.18 Ru0.14 NFs exhibit outstanding electrocatalytic performances and excellent anti-poisoning abilities. The specific activities for the methanol oxidation reaction (MOR) (7.65 mA cm-2 ) and ethanol oxidation reaction (EOR) (7.90 mA cm-2 ) are 6.0 and 7.1 times higher than commercial Pt/C, respectively. The CO stripping experiment and the chronoamperometric (5000 s) demonstrate the superior anti-poisoning property and durability performance. Density functional theory calculations confirm that high metallization degree leads to the decrease of d-band center, the promotion of oxidation of CO, and improvement of the inherent activity and anti-poisoning ability. A Ru-rich edge exposes abundant high index facets to accelerate the reaction kinetics of rate-determining steps by decreasing the energy barrier for forming *HCOOH (MOR) and CC bond breaking (EOR).

AM22, a novel synthetic microRNA, inhibits the proliferation of colorectal cancer cells by targeting core binding factor subunit ß (CBFB).

Our previous studies have revealed the important roles of the nonseed regions of microRNAs (miRNAs) in gene regulation, which provided novel insight into the development of miRNA analogs for cancer therapy. Here, we altered each nucleotide in the nonseed region of miR-34a and obtained novel synthetic miRNA analogs. Among them, AM22, with a base alteration from G to C at the 17th nucleotide of miR-34a, showed extensive antiproliferative activity against several colorectal tumor cell lines and achieved effective inhibition of core binding factor subunit ß (CBFB) expression. Subsequent investigations demonstrated that AM22 directly targeted CBFB by binding to its 3'-untranslated region (3'-UTR). Inhibition of CBFB showed obvious antiproliferative activity on HCT-116 and SW620 cells. Furthermore, the antiproliferative effects of AM22 on these cells were also measured in xenograft mouse models. In conclusion, this study identified AM22 as a potential antitumor miRNA by targeting CBFB and provided a new design approach for miRNA-based cancer treatment by changing the nonseed region of miRNA.

Bendamustine versus chlorambucil in treatment of chronic lymphocytic leukaemia in China: a randomized, open-label, parallel-controlled, phase III clinical trial.

BACKGROUND: Chronic lymphoblastic leukemia (CLL) is the most common adult leukemia and mainly affects the elderly. Chemoimmunotherapy still has a role in the standard frontline therapy for specific population. However, the clinical activity of bendamustine has not been investigated in unfit Chinese patients with CLL. This study aimed to compare the efficacy and safety of bendamustine versus chlorambucil for untreated Chinese patients with Binet stage B/C CLL. METHODS: In this multi-center, randomized, open-label, parallel-controlled, phase III trial, patients with previously untreated CLL were enrolled and randomly assigned (1:1) to receive bendamustine or chlorambucil. The primary endpoint was the objective response rate. Secondary endpoints included progression-free survival, the duration of response, and overall survival. Adverse events were recorded to evaluate safety. RESULTS: Of 158 screened patients, 147 were enrolled and randomly allocated to receive bendamustine (n = 72) or chlorambucil (n = 75). After a median follow-up of 25.6 months (IQR 12.5-27.7), 69.0% (95% CI, 56.9-79.5) of bendamustine-treated patients achieved objective response and 37.0% (95% CI, 26.0-49.1) of chlorambucil with a difference of 32.0% (95%CI: 16.6-47.5), demonstrating the superiority of bendamustine to chlorambucil (p < 0.001). The median progression-free survival was longer for bendamustine (16.5 months; 95% CI, 11.3-24.7) versus chlorambucil (9.6 months; 95% CI, 8.7-11.8; p < 0.001). A longer median duration of response was seen in those receiving bendamustine (19.2 months; 95% CI, 11.8-29.1) than chlorambucil (10.7 months; 95% CI, 5.6-13.6; p = 0.0018). Median overall survival was not reached in either group. Overall survival at 18 months was 88% for bendamustine versus 85% for chlorambucil. Most common adverse events in both groups were neutropenia and thrombocytopenia. CONCLUSION: In untreated Chinese patients with Binet stage B/C CLL, bendamustine induced the better objective response and resulted in longer progression-free survival than chlorambucil. Overall, these results validate the role of bendamustine as an effective and safe first-line therapy in this population.

N-Doped MoS2 Nanoflowers for Efficient Cr(VI) Removal.

The removal of Cr(VI) has attracted extensive attention since it causes serious harm to public health. Herein, we report a two-step method to synthesize N-doped MoS2 nanoflowers (NFs) with controllable sizes, which are first utilized for Cr(VI) removal and display outstanding removal performance. The N-MoS2 NFs with an average size of 40 nm (N-MoS2 NFs-40 nm) can rapidly remove Cr(VI) in 15 min under optimal conditions. The maximum adsorption capacity of N-MoS2 NFs-40 nm can reach 787.41 mg·g-1, which is significantly larger than that of N-MoS2 NFs-150 and -400 nm (314.46 and 229.88 mg·g-1). Meanwhile, N-MoS2 NFs-400 nm have a higher maximum adsorption capacity than pure MoS2 NFs-400 nm (172.12 mg·g-1). In this adsorption/reduction process, N-MoS2 NFs have abundant adsorption sites due to a high surface area. N doping can generate more sulfur vacancy defects in the MoS2 NF structure to accelerate electron transfer and enhance the reduction of Cr(VI) to low-toxicity Cr(III). This study provides a facile approach to fabricating N-MoS2 nanoflowers and demonstrates their superior removal ability for Cr(VI).

Real-Time Non-Contact Millimeter Wave Radar-Based Vital Sign Detection.

In this paper, the extraction of the life activity spectrum based on the millimeter (mm) wave radar is designed to realize the detection of target objects and the threshold trigger module. The maximum likelihood estimation method is selected to complete the design of the average early warning probability trigger function. The threshold trigger module is designed for the echo signal of static objects in the echo signal. It will interfere with the extraction of Doppler frequency shift results. The moving target detection method is selected, and the filter is designed. The static clutter interference is filtered without affecting the phase difference between the detection sequences, and the highlight target signal is improved. The frequency and displacement of thoracic movement are used as the detection data. Through the Fourier transform calculation of the sequence, the spectrum value is extracted within the estimated range of the heartbeat and respiration spectrum, and the heartbeat and respiration signals are picked up. The proposed design uses Modelsim and Quartus for CO-simulation to complete the simulation verification of the function, extract the number of logical units occupied by computing resources, and verify the algorithm with the vital signs experiment. The heartbeat and respiration were detected using the sports bracelet; the relative errors of heartbeat detection were 0-6.3%, the respiration detection was 0-9.5%, and the relative errors of heartbeat detection were overwhelmingly less than 5%.

High-Sensitivity Liquid Dielectric Characterization Differential Sensor by 1-Bit Coding DGS.

This paper presents two devices to detect the liquid dielectric characterization. The differential method was used to enhance the robustness and reduce tolerance. A basic sensor based on defected ground structure (DGS) was designed and the optimization for the squares of the DGS via adaptive genetic algorithm was applied to enhance the performance of the microwave sensor, which was shown by the difference of the two resonant frequencies. Furthermore, the electric field distribution was enhanced. Glass microcapillary tubes were used to hold samples to provide an environment of non-invasive. The optimized device exhibited the sensitivity of 0.076, which is more than 1.52 times than the basic structure. It could be considered a sensitive and robust sensor with quick response time for liquid dielectric characterization.

Chapter Open for the Excited-State Intramolecular Thiol Proton Transfer in the Room-Temperature Solution.

We report here, for the first time, the experimental observation on the excited-state intramolecular proton transfer (ESIPT) reaction of the thiol proton in room-temperature solution. This phenomenon is demonstrated by a derivative of 3-thiolflavone (3TF), namely, 2-(4-(diethylamino)phenyl)-3-mercapto-4H-chromen-4-one (3NTF), which possesses an -S-H···O═ intramolecular H-bond (denoted by the dashed line) and has an S1 absorption at 383 nm. Upon photoexcitation, 3NTF exhibits a distinctly red emission maximized at 710 nm in cyclohexane with an anomalously large Stokes shift of 12 230 cm-1. Upon methylation on the thiol group, 3MeNTF, lacking the thiol proton, exhibits a normal Stokes-shifted emission at 472 nm. These, in combination with the computational approaches, lead to the conclusion of thiol-type ESIPT unambiguously. Further time-resolved study renders an unresolvable (<180 fs) ESIPT rate for 3NTF, followed by a tautomer emission lifetime of 120 ps. In sharp contrast to 3NTF, both 3TF and 3-mercapto-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (3FTF) are non-emissive. Detailed computational approaches indicate that all studied thiols undergo thermally favorable ESIPT. However, once forming the proton-transferred tautomer, the lone-pair electrons on the sulfur atom brings non-negligible nπ* contribution to the S1' state (prime indicates the proton-transferred tautomer), for which the relaxation is dominated by the non-radiative deactivation. For 3NTF, the extension of π-electron delocalization by the diethylamino electron-donating group endows the S1' state primarily in the ππ* configuration, exhibiting the prominent tautomer emission. The results open a new chapter in the field of ESIPT, covering the non-canonical sulfur intramolecular H-bond and its associated ESIPT at ambient temperature.

miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis.

Although a number of studies have revealed the important roles of miR-34a in cancer, the regulatory roles of miR-34a in cancer immune response remain largely unknown. Our present study demonstrated a mechanism underlying miR-34a-mediated cancer immune evasion via a SIRT1/NF-κB/B7-H3/TNF-α axis. miR-34a upregulated B7-H3, an important immune checkpoint molecule, through direct inhibition of SIRT1 and consequent acetylation of NF-κB subunit p65 (a-p65), which promoted B7-H3 transcription by direct binding to its promoter. The elevated B7-H3 induced production of pro-inflammatory cytokines including TNF-α. This was further confirmed in the colon of Mir34a-deficient mice, where Sirt1 expression was boosted, and the expressions of a-p65, B7h3, and Tnf were repressed. Consequently, the in vivo inhibitory activity of miR-34a on colorectal cancer (CRC) was eradicated by the reinforced B7-H3 and TNF-α. In conclusion, our study uncovered an etiological mechanism underlying miR-34a-mediated CRC immune evasion through inhibition of SIRT1 and promotion of NF-κB/B7-H3/TNF-α axis.

B7-H3 is spliced by SRSF3 in colorectal cancer.

B7-H3, an important co-inhibitor, is abnormally highly expressed in a variety of malignancies. The antibodies targeting B7-H3 have exhibited beneficial therapeutic effects in clinical trials. Therefore, discovery of the regulatory factors in B7-H3 expression may provide new strategies for tumor therapy. Here, we investigated the splicing factors involved in the splicing of B7-H3. By individual knockdown of the splicing factors in colorectal cancer (CRC) cells, we found that B7-H3 expression was markedly inhibited by SRSF3 and SRSF8, especially SRSF3. Then we found that both SRSF3 and B7-H3 were highly expressed in CRC tissues. Moreover, high-expression of either SRSF3 or B7-H3 was significantly correlated with poor prognosis of patients. The expression of B7-H3 mRNA and protein were evidently reduced by SRSF3 silence, but were enhanced by overexpression of SRSF3 in both HCT-116 and HCT-8 cells. The results from the RNA immunoprecipitation (RIP) assays demonstrated that SRSF3 protein directly binds to B7-H3 mRNA. In addition, we constructed a minigene recombinant plasmid for expressing B7-H3 exons 3-6. We found that SRSF3 contributed to the retention of B7-H3 exon 4. These findings demonstrate that SRSF3 involves in the splicing of B7-H3 by directly binding to its exon 4 and/or 6. It may provide novel insights into the regulatory mechanisms of B7-H3 expression and potential strategies for the treatment of CRC.

Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia.

BACKGROUND: Epigenetic dysregulation plays important roles in leukemogenesis and the progression of acute myeloid leukemia (AML). Histone acetyltransferases (HATs) and histone deacetylases (HDACs) reciprocally regulate the acetylation and deacetylation of nuclear histones. Aberrant activation of HDACs results in uncontrolled proliferation and blockade of differentiation, and HDAC inhibition has been investigated as epigenetic therapeutic strategy against AML. METHODS: Cell growth was assessed with CCK-8 assay, and apoptosis was evaluated by flow cytometry in AML cell lines and CD45 + and CD34 + CD38- cells from patient samples after staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI). EZH2 was silenced with short hairpin RNA (shRNA) or overexpressed by lentiviral transfection. Changes in signaling pathways were detected by western blotting. The effect of chidamide or EZH2-specific shRNA (shEZH2) in combination with adriamycin was studied in vivo in leukemia-bearing nude mouse models. RESULTS: In this study, we investigated the antileukemia effects of HDAC inhibitor chidamide and its combinatorial activity with cytotoxic agent adriamycin in AML cells. We demonstrated that chidamide suppressed the levels of EZH2, H3K27me3 and DNMT3A, exerted potential antileukemia activity and increased the sensitivity to adriamycin through disruption of Smo/Gli-1 pathway and downstream signaling target p-AKT in AML cells and stem/progenitor cells. In addition to decreasing the levels of H3K27me3 and DNMT3A, inhibition of EZH2 either pharmacologically by chidamide or genetically by shEZH2 suppressed the activity of Smo/Gli-1 pathway and increased the antileukemia activity of adriamycin against AML in vitro and in vivo. CONCLUSIONS: Inhibition of EZH2 by chidamide has antileukemia activity and increases the chemosensitivity to adriamycin through Smo/Gli-1 pathway in AML cells (Fig. 5). These findings support the rational combination of HDAC inhibitors and chemotherapy for the treatment of AML.

Concomitant inhibition of B7-H3 and PD-L1 expression by a novel and synthetic microRNA delivers potent antitumor activities in colorectal tumor models.

The families of miR-34 and miR-449 share the same seed region. However, the members showed differential effects on the expression of B7-H3 and PD-L1 in HCT-116 cells. Using miR-34a as a template, the non-seed region was modified by nucleotide alteration, yielding four synthetic microRNA (miRNA) analogs. Among those, NS-MX3, with a base alteration from G to C at the 18th locus of miR-34a, showed the most potent inhibition on both B7-H3 and PD-L1 expression. Subsequent investigations demonstrated that NS-MX3 had a broad anti-proliferation activity against several colorectal tumor cell lines and its antitumor effect was consistently reflected by tumor growth inhibition (TGI) in the HCT-116 xenograft model. In addition, NS-MX3 displayed a synergistic effect on TGI when combined with bevacizumab or regorafenib. Further analysis revealed that the superior antitumor activity of NS-MX3 was correlated to concomitant suppression of both B7-H3 and PD-L1 expression in tumor tissues. Taken together, the present study indicates that the non-seed region of miRNAs plays an important role in the regulation of checkpoint genes, thus showcasing single nucleotide alteration of the non-seed region as a promising approach to discover and develop novel immunotherapies.

Broadening the Horizon of the Bell-Evans-Polanyi Principle towards Optically Triggered Structure Planarization.

Finding a relationship between kinetics and thermodynamics may be difficult. However, semi-empirical rules exist to compensate for this shortcoming, among which the Bell-Evans-Polanyi (B-E-P) principle is an example for reactions involving bond breakage and reformation. We expand the B-E-P principle to a new territory by probing photoinduced structure planarization (PISP) of a series of dibenz[b,f]azepine derivatives incorporating bent-to-planar and rotation motion. The latter involves twisting of the partial double bond character, thereby inducing a barrier that is substituent dependent at the para N-phenyl position. The transition-state structure and frequency data satisfy and broaden the B-E-P principle to PISP reactions without bond rearrangement. Together with dual emissions during PISP, this makes possible harnessing of the kinetics/thermodynamics relationship and hence ratiometric luminescence properties for excited-state structural transformations.

High-Sensitivity, Quantified, Linear and Mediator-Free Resonator-Based Microwave Biosensor for Glucose Detection.

This article presents a high-sensitivity, quantified, linear, and mediator-free resonator-based microwave biosensor for glucose sensing application. The proposed biosensor comprises an air-bridge-type asymmetrical differential inductor (L) and a center-loaded circular finger-based inter-digital capacitor (C) fabricated on Gallium Arsenide (GaAs) substrate using advanced micro-fabrication technology. The intertwined asymmetrical differential inductor is used to achieve a high inductance value with a suitable Q-factor, and the centralized inter-digital capacitor is introduced to generate an intensified electric field. The designed microwave sensor is optimized to operate at a low resonating frequency that increases the electric field penetration depth and interaction area in the glucose sample. The microwave biosensor is tested with different glucose concentrations (0.3-5 mg/ml), under different ambient temperatures (10-50 °C). The involvement of advanced micro-fabrication technology effectively miniaturized the microwave biosensor (0.006λ0 × 0.005λ0) and enhanced its filling factor. The proposed microwave biosensor demonstrates a high sensitivity of 117.5 MHz/mgmL-1 with a linear response (r2 = 0.9987), good amplitude variation of 0.49 dB/mgmL-1 with a linear response (r2 = 0.9954), and maximum reproducibility of 0.78% at 2 mg/mL. Additionally, mathematical modelling was performed to estimate the dielectric value of the frequency-dependent glucose sample. The measured and analyzed results indicate that the proposed biosensor is suitable for real-time blood glucose detection measurements.

Mono-Heteroatom Substitution for Harnessing Excited-State Structural Planarization of Dihydrodibenzo[a,c]phenazines.

With the aim of generalizing the structure-properties relationship of bending heterocyclic molecules that undergo prominent photoinduced structural planarization (PISP), a series of new dihydrodibenzo[ac]phenazine derivatives in which one nitrogen atom is replaced by oxygen (PNO), sulfur (PNS), selenium (PNSe), or dimethylmethanediyl (PNC) was strategically designed and synthesized. Compounds PNO, PNS, and PNSe have significantly nonplanar geometries in the ground state, which undergo PISP to give a planarlike conformer and hence a large emission Stokes shift. A combination of femtosecond early relaxation dynamics and computational approaches established an R*→I* (intermediate)→P* sequential kinetic pattern for PNS and PNSe, whereas PNO undergoes R*→P* one-step kinetics. The polarization ability of the substituted heteroatoms, which is in the order O

Haploidentical haematopoietic stem cell transplantation for thalassaemia major based on an FBCA conditioning regimen.

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available curative therapy for patients with thalassaemia major. With the progress in human leucocyte antigen (HLA) antigen typing technology and supportive care, the outcomes of thalassaemia major have greatly improved in recent years, even in high-risk patients. However, the problem of finding a suitable donor is still a major obstacle to curing these patients. In recent decades, the lack of available HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT in haematological malignancies. Recently, we explored the effect of HD HSCT to eight children with thalassaemia major based on the FBCA conditioning regimen (fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is usually used in leukaemia patients receiving haploidentical HSCT in our centre. So far, all of the transplanted patients have a stable engraftment and are transfusion independent in daily life. This encouraging result has revised our previous conception about haploidentical HCST for thalassaemia major and strongly suggests that HD HSCT is a feasible and safe method for thalassaemia major patients.

Numerical investigation of nematic liquid crystals in the THz band based on EIT sensor.

This paper introduces the concept of electromagnetically induced transparency (EIT) into the permittivity extraction of an anisotropic material-nematic liquid crystal (NLC). A novel two-step strategy is presented to extract the complex permittivity of the NLC at the THz band, which evaluates the relative permittivity tensor from the resonant frequencies and then determines the loss tangent from the quality factor Q of the EIT sensor. The proposed method features high accuracy due to the sharp resonance of the EIT sensor and also high robustness to the thickness of the NLC layer because only amplitude rather than phase information of the transmission coefficients is required. The NLC filled EIT sensor shows a sensitivity of 56.8 µm/RIU (the resonance wavelength shift over the refractive index change unit (RIU)) and Figure of Merit (FoM) of 6.92. The uncertainty of the proposed technique in the relative permittivity and loss tangent is 3% and 8.2%, respectively.

A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer.

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility.