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Hydrogen sulfide (H 2 S), as the third gas transporter in biological systems, plays a key role in the regulation of biological cells. Real-time detection of local H 2 S concentration in vivo is an important and challenging task. Herein, we explored a novel and facile strategy to develop a flexible and transparent H 2 S sensor based on gold nanowire (AuNW) and carbon nanotube (CNT) films embedded in poly(dimethylsiloxane) (PDMS) (AuNWs/CNTs/PDMS). Taking the advantage of the sandwich-like nanostructured network of AuNWs/CNTs, the prepared electrochemical sensing platform exhibited desirable electrocatalytic activity toward H 2 S oxidation with a wide linear range (5 nM to 24.9 μM) and a low dete ction limit (3 nM). Furthermore, thanks to the good biocompatibility and flexibility of the sensor, HeLa cells can be cultured directly on the electrode, allowing real-time monitoring of H 2 S released from cells under a stretched state. This work provides a versatile strategy for the construction of stretchable electrochemical sensors, which has potential applications in the study of H 2 S-related signal mechanotransduction and pathological processes.

Serotonin (5-HT) is an essential inhibitory neurotransmitter in vivo that is critical for interneuronal communication of the nervous system. Herein, we constructed an electrochemical cell-sensing platform for 5-HT detection based on MXene/single-walled carbon nanotubes (SWCNTs) nanocomposite. The one-dimensional SWCNTs with good electrical conductivity are uniformly dispersed on the surface and intermediate layers of the two-dimensional MXene to form a tightly heterogeneous heterostructure. The synthesized MXene-SWCNTs could improve the stacking problem of MXene nanosheets and expose more active sites, effectively promoting the conductive properties and electrochemical activity of the composite. The fabricated MXene-SWCNTs/GCE possessed outstanding detection capability for 5-HT with a wide linear range of 4 nM-103.2 μM and a low detection limit of 1.5 nM. Moreover, the sensor was further applied for the real-time monitoring trace amount of 5-HT releasing from different cell lines, which confirmed its promising applications in 5-HT related physiological and pathological fields. MXene-SWCNTs/GCE was developed and applied for the real-time monitoring of trace amounts of 5-HT secreted from living cells., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Dendrobium officinale, often used as a kind of tea for daily drinks, has drawn increasing attention for its beneficial effects. Quality evaluation of D. officinale is of great significance to ensure its health care value and safeguard consumers' interest. Given that traditional analytical methods for assessing D. officinale quality are generally time-consuming and laborious, this study developed a comprehensive strategy, with the advantages of being rapid and efficient, enabling the quality evaluation of D. officinale from different geographical origins using near-infrared (NIR) spectroscopy and chemometrics. As the quality indicators, polysaccharides, polyphenols, total flavonoids, and total alkaloids were quantified. Three types of wavelength selection methods were used for model optimization and these were synergy interval (SI), genetic algorithm (GA), and competitive adaptive reweighted sampling (CARS). From the qualitative perspective, the geographical origins of D. officinale were differentiated by NIR spectroscopy combined with partial least squares-discriminant analysis (PLS-DA) and support vector classification (SVC). The PLS models constructed based on the wavelengths selected by CARS yielded the best performance for prediction of the contents of quality indicators in D. officinale. The root mean square error (RMSEP) and coefficient of determination (R p 2 ) in the independent test sets were 12.7768 g kg -1 and 0.9586, 1.1346 g kg -1 and 0.9670, 0.3938 g kg -1 and 0.8803, 0.0825 and 0.7031 and for polysaccharides, polyphenols, total flavonoids, and total alkaloids, respectively. As for the origin identification, the nonlinear SVC was superior to the linear PLS-DA, with the correct recognition rates in calibration and prediction sets up to 100% and 100%, respectively. The overall results demonstrated the potential of NIR spectroscopy and chemometrics in the rapid determination of quality parameters and geographical origin. This study could provide a valuable reference for quality evaluation of D. officinale in a more rapid and comprehensive manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The connections between pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) constitutes the crucial signaling pathways in the innate immune system. Cytoplasmic nucleic acid sensor melanoma differentiation-associated gene 5 (MDA5) serves as an important pattern recognition receptor in the innate immune system by recognizing viral RNA. MDA5 also plays a role in identifying the cytoplasmic RNA from damaged, dead cancer cells or autoimmune diseases. MDA5's recognition of RNA triggers innate immune responses, induces interferon (IFN) response and a series of subsequent signaling pathways to produce immunomodulatory factors and inflammatory cytokines. Here we review the latest progress of MDA5 functions in triggering anti-tumor immunity by sensing cytoplasmic dsRNA, and recognizing SARS-CoV-2 virus infection for antiviral response, in which the virus utilizes multiple ways to evade the host defense mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin, Cao, Lu, Gao and Ma.)

Although Cisplatin (DDP) is a widely used first-line chemotherapy medication, DDP resistance is one of the main causes of treatment failure in advanced lung cancer. Therefore, it is urgent to identify DDP sensitizers and investigate the underlying molecular mechanisms. Here we utilized DDP-resistant organoids established from tumor biopsies of patients with relapsed lung cancers. In this study, we identified Solamargine as a potential DDP sensitizer through screening a natural product library. Mechanically, Solamargine induced G0/G1-phase arrest and apoptosis in DDP-resistant lung cancer cell lines. Gene expression analysis and KEGG pathway analysis indicated that the hedgehog pathway was suppressed by Solamargine. Moreover, Gli responsive element (GRE) reporter gene assay and BODIPY-cyclopamine binding assay showed that Solamargine inhibited the hedgehog pathway via direct binding to SMO protein. Interestingly, Solamargine and DDP showed a synergetic effect in inhibiting DDP-resistant lung cancer cell lines. Taken together, our work herein revealed Solamargine as a hedgehog pathway inhibitor and DDP-sensitizer, which might provide a new direction for further treatment of advanced DDP-resistant lung cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Shi, Xu, Zhang, Cao, Yu, Li and Xu.)

The treatment of hypersaline oilfield wastewater (HSOW) is a challenge due to its complex composition and low biodegradability, especially in coastal areas. In this study, an HSOW treatment system of gas flotation and biochemistry technology combined with constructed wetland (CW) was investigated. The combined treatment system could efficiently remove COD, NH 4 + -N and oil under high salinity (1.36-2.21 × 10 4 mg/L), with average removal rates of 98.5%, 99.9% and 96%, respectively. Meanwhile, different salinity shaped particular community structures and functions. The abundance of Marivita, Parvibaculum, etc. was highly correlated with salinity. Co-occurrence network resulted that the microorganisms were highly interconnected, and formed a functional group of petroleum degrading. Pseudomonas, Rosevarius, Alternaria, etc. were the key genera. Moreover, functional prospected revealed that high salinity reduced the energy metabolism activity. This study will optimize the combined process and provide the basis for further extraction of high-efficiency degradation strains for HSOW enhanced treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC., Methods: Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles., Results: Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity., Conclusions: Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target for T-cell receptor-engineered T cell (TCR-T) therapy, and targeting the human leukocyte antigen (HLA)-A2 restricted NY-ESO-1 157-165 epitope has yielded remarkable clinical benefits in the treatment of multiple advanced malignancies. Herein, we report the identification of two NY-ESO-1 157-165 epitope-specific murine TCRs obtained from HLA-A * 0201 transgenic mice. NY-ESO-1 157-165 specific TCRs were isolated after vaccinating HLA-A2 transgenic mice with epitope peptides. HZ6 and HZ8 TCRs could specifically bind to NY-ESO-1 157-165 /HLA-A2 and were capable of cytokine secretion with engineered Jurkat T cells and primary T cells upon recognition with K562 target cells expressing the single-chain trimer (SCT) of NY-ESO-1 157-165 /HLA-A2. The reactivity profiles of the HZ6 and HZ8 TCRs were found to be distinct from one another when co-cultured with K562 target cells carrying alanine-substituted NY-ESO-1 157-165 SCTs. The binding characterization revealed that the recognition pattern of the HZ6 TCR to NY-ESO-1 157-165 /HLA-A2 was substantially different from the widely used 1G4 TCR. These findings would broaden the understanding of immunogenicity of the NY-ESO-1 157-165 , and the two identified TCRs may serve as promising candidates for the future development of TCR-T therapy for tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Sun, Wang, Zeng, Cao, Han, Tan and Gao.)

Background: Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues., Methods: We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR)., Results: Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA., Conclusions: In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.

Cathelicidins play pivotal roles in host defense. The discovery of novel cathelicidins is important research; however, despite the identification of many cathelicidins in vertebrates, few have been reported in amphibians. Here we identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an amphibian species, Odorrana andersonii. Produced by posttranslational processing of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence of 'IGRDPTWSHLAASCLKCIFDDLPKTHN' and a molecular mass of 3038.5 Da. Functional analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing promotion in a mouse model with full-thickness skin wounds, accelerating re-epithelialization and granulation tissue formation by enhancing the recruitment of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell migration. This is the first cathelicidin identified from an amphibian that shows potent wound-healing activity. These results will help in the development of new types of wound-healing agents and in our understanding of the biological functions of cathelicidins.

The stress response induced by surgery and anesthesia can inhibit the immune function of the body. Studies have shown that pain can inhibit the proliferation of T cells and weaken the activity of NK cells, resulting in immunosuppression. In this study, flurbiprofen axetil was used for drug intervention. The results showed that flurbiprofen can make the serum TNF- and IL-6 levels significantly reduce, illustrate the application of flurbiprofen axetil can promote the inflammatory balance, inhibit excessive stress reaction, thus contributing to the clinical curative effect and postoperative recovery of patients. The authors have also analyzed treatment of primary spontaneous pneumothorax by using single port thoracoscopy. Based on the analysis of the effect of single hole thoracoscopic surgery, it shows that the average time of single hole thoracoscopic surgery group (49±12.34) min, intraoperative blood loss (32.5±7.32) ml, there was no significant difference between the two groups. The result proved that the technique of single hole thoracoscopic surgery can reduce the injury of the chest wall and the hemostasis time, and reduce the incision scar.

The deregulation of p53 in cancer cells is one of the important factors by which cancer cells escape from the immune surveillance. Cholecystokinin (CCK) has strong bioactivity in the regulation of a number of cell activities. This study tests a hypothesis that CCK interferes with p53 expression to affect the apoptotic process in lung cancer (tumor) cells. In this study, tumor-bearing mice and A549 cells (a tumor cell line) were irradiated. The expression of CCK and p53 in tumor cells was assessed with RT-qPCR and Western blotting. The binding of p300 to the promoter of p53 was evaluated by chromatin immunoprecipitation. We observed that, with a given amount and within a given period, small doses/more sessions of irradiation markedly increased the levels of CCK in the sera and tumor cells, which were positively correlated with the tumor growth in mice and negatively correlated with tumor cell apoptosis. CCK increased the levels of histone acetyltransferase p300 and repressed the levels of nuclear factor-kB at the p53 promoter locus in tumor cells, which suppressed the expression of p53. In conclusion, CCK plays an important role in attenuating the radiation-induced lung cancer cell apoptosis. CCK may be a novel therapeutic target in the treatment of lung cancers.

List mode format is commonly used in modern positron emission tomography (PET) for image reconstruction due to certain special advantages. In this work, we proposed a list mode based regularized relaxed ordered subset (LMROS) algorithm for static PET imaging. LMROS is able to work with regularization terms which can be formulated as twice differentiable convex functions. Such a versatility would make LMROS a convenient and general framework for fulfilling different regularized list mode reconstruction methods. LMROS was applied to two simulated undersampling PET imaging scenarios to verify its effectiveness. Convex quadratic function, total variation constraint, non-local means and dictionary learning based regularization methods were successfully realized for different cases. The results showed that the LMROS algorithm was effective and some regularization methods greatly reduced the distortions and artifacts caused by undersampling.