High-mobility InSnZnO Thin Film Transistors via Introducing Water Vapor Sputtering Gas.

There is always a doubt that introducing water during oxide growing has a positive or negative effect on the properties of oxide films and devices. Herein, a comparison experiment on the condition of keeping the same oxygen atom flux in the sputtering chamber is designed to examine the influences of H2O on In-Sn-Zn-O (ITZO) films and their transistors. In comparison to no-water films, numerous unstable hydrogen-related defects are induced on with-water films at the as-deposited state. Paradoxically, this induction triggers an ordered enhancement in the microstructure of the films during conventional annealing, characterized by a reduction in H-related and vacancy (Vo) defects as well as an increase in film packing density and the M-O network ordering. Ultimately, the no-water thin-film transistors (TFTs) exhibit nonswitching behavior, whereas 5 sccm-water TFT demonstrates excellent electrical performance with a remarkable saturation field-effect mobility (µFE) of 122.10 ± 5.00 cm2·V-1·s-1, a low threshold (Vth) of -2.30 ± 0.40 V, a steep sub-threshold swing (SS) of 0.18 V·dec-1, a high output current (Ion) of 1420 µA, and a small threshold voltage shift ΔVth of -0.77 V in the negative bias stability test (3600 s).

Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Homogeneous and Nanogranular Prussian Blue to Enable Long-Term-Stable Electrochromic Devices.

The increasing demand for the state-of-the-art electrochromic devices has received great interest in synthesizing Prussian blue (PB) nanoparticles with a uniform diameter that exhibit excellent electrochromism, electrochemistry, and cyclability. Herein, we report the controllable synthesis of sub-100 nm PB nanoparticles via the coprecipitation method. The diameter of PB nanoparticles can be modulated by adjusting the reactant concentration, the selection of a chelator, and their purification. The self-assembled nanogranular thin films, homogeneously fabricated by using optimized PB nanoparticles with an average diameter of 50 nm as building blocks via the blade coating technique enable excellent performance with a large optical modulation of 80% and a high coloration efficiency of 417.79 cm2 C-1. It is also demonstrated by in situ and ex situ observations that the nanogranular PB thin films possess outstanding structural and electrochemical reversibility. Furthermore, such nanogranular PB thin films can enjoy the enhanced long-term cycling stability of the PB-WO3 complementary electrochromic devices having a 91.4% optical contrast retention after 16,000 consecutive cycles. This work provides a newly and industrially compatible approach to producing a complementary electrochromic device with extraordinary durability for various practical applications.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

"Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.

BACKGROUND: Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. METHODS: Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. RESULTS: We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. CONCLUSION: This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.

Improved Electrical Resistivity of Atomic-Layer-Deposited Copper Thin Films on Polyimide Substrates by an In Situ ZnO Interlayer.

The low-temperature atomic layer deposition of metal on polymer surfaces is often challenging owing to the deficiency of functional groups and reactivity. Here, the deposition of ALD-Cu employing Cu(hfac)2 and Et2Zn at a low temperature (120 °C) on polyimide (PI) substrates is improved by the utilization of an in situ ultrathin ALD-ZnO buffer layer. A conformal and continuous ALD-Cu thin film with low resistivity (6.07 µΩ cm) is fabricated on an ALD-ZnO/PI substrate. The findings demonstrate that the ALD-ZnO buffer layer provides chemisorption and a nucleation site for the initial growth of ALD-Cu. Transmission electron microscopy and energy-dispersive X-ray analysis reveal that the ALD-ZnO layer plays a buffer role in the fitness of ALD-Cu on PI substrates and its ability to elicit the formation of an ALD-ZnO nanocluster and polar surface. ALD-ZnO can be effectively utilized as a buffer layer for polymer-based ALD-metal processes, showing potential in flexible electronic applications.

Mechanistic Insights into Anion-Induced Electrochromism of Ru(II)-Based Metallo-Supramolecular Polymer.

The metallo-supramolecular polymer (MSP) is considered one of the most promising electrodes for electrochromic devices due to its intrinsically stable redox properties. Nevertheless, despite extensive work focusing on improving the electrochromic and electrochemical properties of MSPs, little experimental evidence exists from in-depth investigations on the anion-induced electrochromism of MSPs. Herein, Ru-based metallo-supramolecular polymer (polyRu) films with excellent electrochromic performance were fabricated through a novel electrochemical deposition method, and the electrochromic mechanism was further understood. The polyRu films possess fast reaction kinetics with a short switching time of 4.0 s (colored) and 2.8 s (bleached) and highly reversible redox properties due to the resulting impacts on the capacitive behaviors (containing surface, near-surface and intercalation pseudo-capacitance) of the perchlorate ions in the electrochromic process. Moreover, the electrochromic degradation of the polyRu films is considered to stem from the numerous nanopores in the film induced by ClO4- transport and the exchange of counter anions from Cl- to ClO4-. In addition, a physical model, revealing the transport of conduction ions and the evolution of the structure and properties of the polyRu film during the electrochromic process, is presented. It is observed that the charge balance of Ru3+ and Ru2+, achieved through the adsorption/desorption of ClO4- on the film, provides electrochromic and electrochemical reversibility to the polyRu film under positive/negative bias. Correspondingly, a transformation from polyRu·(Cl-)2n to polyRu·(ClO4-)x(Cl-)2n-x in the polyRu film is induced by a counter anion exchange from Cl- to ClO4-. Revealing the detailed perchlorate ion transfer kinetics and electrochromic mechanism in this film can offer new insights into the application of metallo-supramolecular polymers in electrochromic devices.

Progress of near-infrared-II fluorescence in precision diagnosis and treatment of colorectal cancer.

Colorectal cancer is a malignant tumour with high incidence and mortality worldwide; therefore, improving the early diagnosis of colorectal cancer and implementing a targeted "individualized treatment" strategy is of great concern. NIR-II fluorescence imaging is a large-depth, high-resolution optical bioimaging tool. Around the NIR-II window, researchers have developed a variety of luminescent probes, imaging systems, and treatment methods with colorectal cancer targeting capabilities, which can be visualized and image-guided in clinical surgery. This article aims to overcome the difficulties in diagnosing and treating colorectal cancer. The present review summarizes the latest results on using NIR-II fluorescence for targeted colorectal cancer imaging, expounds on the application prospects of NIR-II optical imaging for colorectal cancer, and discusses the imaging-guided multifunctional diagnosis and treatment platforms.

Homologous proteins SAPCD2X1 and SAPCD2 have significantly different carcinogenic capacities in human colorectal cancer cells based on structural prediction and functional verification.

We discussed the expression and biological functions of the SAPCD2X1 protein in the HCT116 CRC cell line by bioinformatics analysis and prediction, and biological function verification. Spatial conformation models of SAPCD2X1 and SAPCD2 were predicted using the threading method, ensemble method, and several other protein structure prediction approaches. The conformational similarity between SAPCD2X1 and SAPCD2 was studied, and their functions were predicted. The biological experiments showed that SAPCD2X1 and SAPCD2 were overexpressed in CRC cells. SAPCD2X1-specific antibodies were prepared. The expressions of SAPCD2X1 and SAPCD2 were localized in cells using the immunofluorescence assay. The SAPCD2 and SAPCD2X1 overexpression models were validated using Western Blot and RT-qPCR. We successfully predicted the structures of the SAPCD2X1 and SAPCD2 proteins, and visualized them using the VDM software. It was predicted that the tertiary structure of SAPCD2X1 changed significantly compared with SAPCD2. Alteration of the biological functions of SAPCD2X1 was also predicted due to the changes in the spatial conformation of the protein. Anti-SAPCD2X1 antibody and SAPCD2X1-EGFP and SAPCD2-EGFP recombinant plasmids were established. The overexpression of the two proteins was induced in HCT116 cells using the recombinant plasmids, and verified by RT-qPCR and Western Blot. Meanwhile, the anti-SAPCD2X1 antibody was proved to have a high specificity. The immunofluorescence assay showed that SAPCD2X1 and SAPCD2 are mainly expressed in the cytoplasm. SAPCD2X1 and SAPCD2 exhibited significantly different biological functions in HCT116 cells. SAPCD2 is a carcinogenic protein, while SAPCD2X1 does not affect the proliferation, invasion, and migration of human CRC HCT116 cells.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

[Modulation of autophagy in the rats with acute intracerebral hemorrhage by acupuncture based on JNK pathway].

OBJECTIVE: To investigate the effects of acupuncture on JNK pathway and autophagy level in rats with intracerebral hemorrhage （ICH） and explore the partial mechanism of acupuncture against ICH. METHODS: SD rats were randomly divided into blank group, model group and acupuncture group. Each group was divided into Day 1, Day 3 and Day 7 subgroups respectively, with 5 rats in each group. The autologous blood injection was adopted to duplicate rat model of ICH. In the acupuncture group, the needle was inserted from "Baihui" （GV20） towards "Qubin" （GB7） on the affected side, stimulating for 30 min each time, once daily； the same acupuncture technique was opera-ted in each subgroup for 1, 3 and 7 days, separately. Using Bederson scale, the neurological deficit was evaluated in each group. Western blot was adopted to detect the protein expression levels of Beclin1, LC3Ⅰ/Ⅱ, phosphorylated c-Jun amino-terminal kinase （p-JNK） and the phosphorylated （p）-c-Jun around hematoma lesion of the brain tissue of rats in each group. RESULTS: After treatment, the neurological deficit score of rats in the model group was higher than that of the blank group at each time point （P<0.05）, and the score of the acupuncture group started declining since the 3rd day of treatment when compared with the model group （P<0.05）. At each time point, compared with the blank group, the protein expression levels of LC3Ⅰ/Ⅱ, Beclin1, p-c-Jun and p-JNK was increased （P<0.01）. Compared with the model group, the protein expression level of LC3Ⅰ/Ⅱ was reduced （P<0.05）； the protein expression levels of Beclin1, p-c-Jun and p-JNK was increased （P<0.05, P<0.01） on day 3 and 7 in the acupuncture group. CONCLUSION: Acupuncture can activate the JNK pathway in the brain tissue of rats with ICH and increase the level of autophagy, thereby improving the neurological function of the rats with ICH.

One-Pot Synthesis and Excited-State Dynamics of Null Exciton-Coupled Diketopyrrolopyrroles Oligo-Grids.

Exciton coupling in molecular aggregates plays a vital role in impacting and fine-tuning optoelectronic materials and their efficiencies in devices. A versatile platform to decipher aggregation-property relationships is built around multichromophoric architectures. Here, a series of cyclic diketopyrrolopyrrole (DPP) oligomers featuring nanoscale gridarene structures and rigid bifluorenyl spacers are designed and synthesized via one-pot Friedel-Crafts reaction. DPP dimer [2]Grid and trimer [3]Grid, which are cyclic rigid nanoarchitectures of rather different sizes, are further characterized via steady-state and time-resolved absorption and fluorescence spectroscopies. They exhibit monomer-like spectroscopic signatures in the steady-state measurements, from which null exciton couplings are derived. Moreover, in an apolar solvent, high fluorescence quantum yields and excited-state dynamics that resembled DPP monomer are gathered. In a polar solvent, the localized singlet excited state on a single DPP dissociates into the adjacent null coupling DPP with charge transfer characteristics. This pathway facilitates the evolution of the symmetry-broken charge-separated state (SB-CS). Notable is the fact that the SB-CS of [2]Grid is, on one hand, in equilibrium with the singlet excited state and promotes, on the other hand, the formation of the triplet excited state with a yield of 32% via charge recombination.

Flexible but Refractory Single-Crystalline Hyperbolic Metamaterials.

The fabrication of flexible single-crystalline plasmonic or photonic components in a scalable way is fundamentally important to flexible electronic and photonic devices with high speed, high energy efficiency, and high reliability. However, it remains a challenge. Here, we have successfully synthesized flexible single-crystalline optical hyperbolic metamaterials by directly depositing refractory nitride superlattices on flexible fluorophlogopite-mica substrates with magnetron sputtering. Interestingly, these flexible hyperbolic metamaterials show dual-band hyperbolic dispersion of dielectric constants with small dielectric losses and high figures of merit in the visible to near-infrared ranges. More importantly, the optical properties of these nitride-based flexible hyperbolic metamaterials show remarkable stability during 1000 °C heating or after being bent 1000 times. Therefore, the strategy developed in this work offers an easy and scalable route for fabricating flexible, high-performance, and refractory plasmonic or photonic components, which can significantly expand the applications of current electronic and photonic devices.

Addressing the Conflict between Mobility and Stability in Oxide Thin-film Transistors.

Amorphous oxide semiconductor thin-film transistors (AOS TFTs) are ever-increasingly utilized in displays. However, to bring high mobility and excellent stability together is a daunting challenge. Here, the carrier transport/relaxation bilayer stacked AOS TFTs are investigated to solve the mobility-stability conflict. The charge transport layer (CTL) is made of amorphous In-rich InSnZnO, which favors big average effective coordination number for all cations and more edge-shared structures for better charge transport. Praseodymium-doped InSnZnO is used as the charge relaxation layer (CRL), which substantially shortens the photoelectron lifetime as revealed by femtosecond transient absorption spectroscopy. The CTL and CRL with the thickness suitable for industrial production respectively afford minute potential barrier fluctuation for charge transport and fast relaxation for photo-generated carriers, resulting in transistors with an ultrahigh mobility (75.5 cm2 V-1 s-1 ) and small negative-bias-illumination-stress/positive-bias-temperature-stress voltage shifts (-1.64/0.76 V). The design concept provides a promising route to address the mobility-stability conflict for high-end displays.

Identification of Gene Signature-Related Oxidative Stress for Predicting Prognosis of Colorectal Cancer.

Background: Colorectal cancer (CRC) is the third most common cancer. Nearly a decade of studies had shown that cancer regimens tailored to molecular and pathological features lead to improved overall survival. Oxidative stress (OS) refers to a state in which oxidation and antioxidant effects are unbalanced in the body. However, the molecular mechanism of OS-related CRC remains unclear. Methods: Univariate Cox regression analysis gained OS signature genes related to CRC prognosis, and then, different CRC molecular subtypes were obtained by consensus clustering analysis. Differential expression analysis and least absolute shrinkage and selection operator (LASSO) algorithm were used to obtain prognostic-related signature genes. Significantly, risk score was calculated by RiskScore = Σßi × Expi. Moreover, the Kaplan-Meier survival analysis, immune cell infiltration, and sensitivity to treatment regimens were performed to assess the model's validity and adaptability. Finally, RiskScore incorporated clinicopathological features to further improve prognostic models and survival prediction. Results: 63 OS-related prognostic genes were obtained, and four distinct molecular subtypes of CRC were identified based on the expression characteristics. 230 differentially expressed genes (DEGs) between different molecular subtypes were compressed by LASSO algorithm, and finally, 6 OS-related genes were obtained. The Kaplan-Meier survival analysis indicated that the high RiskScore groups had poorer prognosis and the RiskScore model showed better predictive performance in all three other independent datasets. Moreover, immunotherapy/chemosensitivity analysis found that the low-risk group was more sensitive to different treatment options and could achieve better treatment outcomes. Conclusion: Oxidative stress-related RiskScore model built in this work has good predictive performance for CRC.

Modulating the nonlinear absorption response of SnOx thin films via phase engineering.

Phase (composition) is known to play a key role in determining the electronic and optical properties of amorphous oxide semiconductors. In this work, modulating the ultrafast nonlinear optical (NLO) response of SnO2 and SnO thin films by tuning oxygen partial pressure during film sputtering is explored. Femtosecond Z-scan results demonstrate that intermediate phases have no profound impact on the two-photon absorption (TPA) response of SnO2 and SnO films. Interestingly, the magnitude of the effective nonlinear absorption coefficient (ßeff) of both intermediate SnO2-x and SnOx are enhanced after the change of Sn2+/Sn4+ composition ratio, as measured by picosecond Z-scan technique. Femtosecond degenerate pump-probe measurements show that intermediate phases accelerate the carrier trapping and improve the defect-related carrier absorption in SnOx (SnO-rich) film, while intermediate phase suppress the TPA response of SnO2-x (SnO2-rich) films, therefore carrier-induced absorption dominates the NLO behavior of SnO2-x film on picosecond regime. Our results indicate a simple and effective way to modulate the NLO response of transparent conductive oxide SnO2 and SnO.

Enhanced Efficiency of Exciplex Emission from a 9-Phenylfluorene Derivative.

The exciplex-thermally activated delayed fluorescence (exciplex-TADF) system is an excellent candidate for the fabrication of high-efficiency organic light-emitting diodes (OLEDs) because of its more easily achieved small singlet-triplet energy splitting (ΔEST) and doping control. However, exciplex-TADF is still faced with the problems of low external quantum efficiency (ηext) and unclear effect of structure modification in electron acceptors. Herein, we provide a steric hindrance increase strategy to obtain high-efficiency exciplex emissions. Through introducing a 9-phenylfluorene group into N-ethylcarbazole of the dicyano-substituted 9-phenylfluorene, an electron acceptor material with increased steric hindrance is obtained, which helps the exciplex harvest a larger driving force and higher emission efficiencies. Encouragingly, the obtained OLED displays a maximum ηext of 25.8%, which is one of the best efficiency values among reported exciplex-OLEDs, simultaneously possessing excellent current efficiency of 83.6 cd A-1 and power efficiency of 93.7 lm W-1. It is expected that this work will offer a new avenue for designing electron acceptors for highly efficient exciplex emissions.

Early diagnosis value of peripheral blood PPARγ combined with IFN-γ detection for tuberculosis infection in patients with end-stage renal disease / 中国热带医学

@#Abstract: Objective　To explore the early diagnostic value of peripheral blood peroxisome proliferator-activated receptor γ (PPARγ) combined with γ-interferon (IFN-γ) release assay (IGRA) in the diagnosis of pulmonary tuberculosis in patients with end-stage renal disease (ESRD), and to provide reference for clinical diagnosis and treatment. Methods　From January 2019 to December 2021, 70 ESRD patients with suspicious symptoms of pulmonary tuberculosis were treated at Hebei Chest Hospital were selected as the research objects. According to the examination results, they were divided into ESRD group (40 cases) and ESRD complicated by pulmonary tuberculosis (40 cases, comorbidity group). In addition, 40 cases with pulmonary tuberculosis were used as the PTB group. All three groups of patients underwent IGRA test, and the peripheral blood PPARγ level was detected by enzyme-linked immunosorbent assay, and the diagnostic value of PPARγ combined with IGRA test for ESRD patients with pulmonary tuberculosis was explored. Results The expression level of PPARγ and IFN-γ content in the PTB group and the comorbidity group were obviously higher than those in the ESRD group (P<0.05), while the differences in PPARγ expression level and IFN-γ content between the PTB and comorbidity groups were not statistically significant (P>0.05). The ROC curve showed that the areas under the curve (AUC) of PPARγ and IGRA in the diagnosis of end-stage renal disease combined with tuberculosis were 0.823 (95%CI: 0.722-0.925) and 0.773 (95%CI: 0.662-0.883), respectively, and the AUC of combined detection was 0.928 (95%CI: 0.871-0.984), which was better than that of PPARγ and IGRA alone (Z/P=2.057/0.039, 2.843/0.005). The Kappa values of serum PPARγ and IGRA test compared with the clinical gold standard results in the diagnosis of ESRD complicated with pulmonary tuberculosis were 0.557 and 0.444 (P<0.05). The combined screening of ESRD with pulmonary tuberculosis was consistent with the clinical gold standard (Kappa=0.661, P<0.05). Among the 30 ESRD patients complicated with pulmonary tuberculosis, the sensitivity of PPARγ combined with IGRA test in diagnosis of ESRD complicated with pulmonary tuberculosis was 93.33% (28/30), which was higher than 70.00% (21/30) of PPARγ and 66.67% (20/30) of IGRA test alone (P<0.05). Conclusions Peripheral blood PPARγ and IGRA tests have certain diagnostic value for ESRD complicated with tuberculosis, and the combined detection of the two can improve the sensitivity and reduce the rate of missed diagnosis, which is worthy of clinical promotion.

Multidrug resistance genes screening of pancreatic ductal adenocarcinoma based on sensitivity profile to chemotherapeutic drugs.

BACKGROUNDS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types and chemotherapeutic drug resistance is a stumbling block in improving the overall survival of PDAC patients. The nature of specific drug resistant subpopulation within pancreatic ductal adenocarcinoma is believed to be partly attributed to epithelial-mesenchymal transition (EMT) and cell stemness. Various PDAC cell lines show various degrees of resistance to chemotherapeutic agents including gemcitabine (GEM) and 5-fluorouracil (5-FU). In-depth understanding of drug resistance mechanisms and profile heterogeneities could lead to the development of novel and precise therapeutic strategies for addressing the chemo-resistant dilemma in PDAC patients. METHODS: Cytotoxicity assays were performed by CCK8 in ten common PDAC cell lines including AsPC-1, BxPC-3, CAPAN-1, CFPAC, HPAFII, MIA PaCa-2, PANC-1, Patu-8988, SW1990 and T3M4. RNA-seq data of the ten cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE) database and subsequently analyzed for differentially expressed genes (DEGs). Based on first-line chemotherapy regimens of PDAC, DEGs between resistant and sensitive cell lines were validated by qRT-PCR. Enriched pathways of differentially expressed genes between the resistant and sensitive cell lines were acquired by Metascape database. RESULTS: We found that the top two toxic drugs for PDAC cell lines were paclitaxel (PTX) and GEM. Among the ten PDAC cell lines, SW1990 was the most resistant PDAC cell line with the highest IC50 levels for three drugs, while MIA PaCa-2 and BxPC-3 were the most sensitive PDAC cell lines. Differential expression analysis revealed the highest number of DEGs associated with cisplatin (CIS) sensitivity up to 642 genes, of which 181 genes were upregulated and 461 genes were downregulated in CIS-resistant cell lines. The least number of DEGs are associated with GEM sensitivity, of which 37 genes were highly expressed in GEM-resistant PDAC cell lines and 25 genes were lowly expressed. Enrichment analysis of the DEGs revealed that pathways associated with drug resistance were mainly extracellular matrix and cell-cell junction related pathways. CONCLUSIONS: PDAC cell lines showed diverse sensitivities to commonly used chemotherapeutic agents, which was caused by differential gene expression between the resistant and sensitive cell lines. The heterogeneity and its associated genes were enriched in extracellular matrix and cell-cell junction related pathways. Our study first portrayed the sensitivity profile to chemotherapeutic drugs of PDAC, which would benefit the chemoresistance mechanism study by reemphasizing the vital role of extracellular matrix and cell-cell junction related pathways and helping the selection of suitable PDAC cell lines.