Skin-Inspired Textile Electronics Enable Ultrasensitive Pressure Sensing.

Wearable pressure sensors have attracted great interest due to their potential applications in healthcare monitoring and human-machine interaction. However, it is still a critical challenge to simultaneously achieve high sensitivity, low detection limit, fast response, and outstanding breathability for wearable electronics due to the difficulty in constructing microstructure on a porous substrate. Inspired by the spinosum microstructure of human skin for highly-sensitive tactile perception, a biomimetic flexible pressure sensor is designed and fabricated by assembling MXene-based sensing electrode and MXene-based interdigitated electrode. The product biomimetic sensor exhibits good flexibility and suitable air permeability (165.6 mm s-1), comparable to the typical air permeable garments. Benefiting from the two-stage amplification effect of the bionic intermittent structure, the product bionic sensor exhibits an ultrahigh sensitivity (1368.9 kPa-1), ultrafast response (20 ms), low detection limit (1 Pa), and high-linearity response (R2 = 0.997) across the entire sensing range. Moreover, the pressure sensor can detect a wide range of human motion in real-time through intimate skin contact, providing essential data for biomedical monitoring and personal medical diagnosis. This principle lays a foundation for the development of human skin-like high-sensitivity, fast-response tactile sensors.

Improvement of differential modal gain in a ring-core few-mode erbium-doped polymer optical waveguide amplifier.

A few-mode erbium-doped waveguide amplifier (FM-EDWA) with a confined Er3+ doped ring structure is proposed to equalize the differential modal gain (DMG). The FM-EDWA amplifying three spatial modes (LP01, LP11a and LP11b) is optimized by genetic algorithm and fabricated using precise lithography overlay alignment technology. We observe gain values of over 14 dB for all modes with DMG of 0.73 dB at 1529 nm pumped only with LP01 for the power of 200 mW. Furthermore, a flat gain of more than 10 dB is demonstrated across 1525-1565 nm, with a sufficiently low DMG of less than 1.3 dB.

ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation.

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6.

Helicobacter pylori (H. pylori, Hp) has been designated a class I carcinogen and is closely associated with severe gastric diseases. During colonization in the gastric mucosa, H. pylori develops immune escape by inducing host immune tolerance. The gastric epithelium acts as the first line of defense against H. pylori, with Toll-like receptors (TLRs) in gastric epithelial cells being sensitive to H. pylori components and subsequently activating the innate immune system. However, the mechanism of immune tolerance induced by H. pylori through the TLR signalling pathway has not been fully elucidated. In this research, we detected the expression of TLRs and inflammatory cytokines in GES-1 cells upon sustained exposure to H. pylori or H. pylori lysate from 1 to 30 generations and in Mongolian gerbils infected with H. pylori for 5 to 90 weeks. We found that the levels of TLR6 and inflammatory cytokines first increased and then dropped during the course of H. pylori treatment in vitro and in vivo. The restoration of TLR6 potentiated the expression of IL-1ß and IL-8 in GES-1 cells, which recruited neutrophils and reduced the colonization of H. pylori in the gastric mucosa of gerbils. Mechanistically, we found that persistent infection with H. pylori reduces the sensitivity of TLR6 to bacterial components and regulates the expression of inflammatory cytokines in GES-1 cells through TLR6/JNK signaling. The TLR6 agonist obviously alleviated inflammation in vitro and in vivo. Promising results suggest that TLR6 may be a potential candidate immunotherapy drug for H. pylori infection.

Discovery, Total Synthesis, and Anti-inflammatory Evaluation of Naturally Occurring Naphthopyrone-Macrolide Hybrids as Potent NLRP3 Inflammasome Inhibitors.

Numerous clinical disorders have been linked to the etiology of dysregulated NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Despite its potential as a pharmacological target, modulation of NLRP3 activity remains challenging. Only a sparse number of compounds have been reported that can modulate NLRP3 and none of them have been developed into a commercially available drug. In this research, we identified three potent NLRP3 inflammasome inhibitors, gymnoasins A-C (1-3), with unprecedented pentacyclic scaffolds, from an Antarctic fungus Pseudogymnoascus sp. HDN17-895, which represent the first naturally occurring naphthopyrone-macrolide hybrids. Additionally, biomimetic synthesis of gymnoasin A (1) was also achieved validating the chemical structure and affording ample amounts of material for exhaustive bioactivity assessments. Biological assays indicated that 1 could significantly inhibited in vitro NLRP3 inflammasome activation and in vivo pro-inflammatory cytokine IL-1ß release, representing a valuable new lead compound for the development of novel therapeutics with the potential to inhibit the NLRP3 inflammasome.

Versatile Electronic Textile Enabled by a Mixed-Dimensional Assembly Strategy.

Electronic textiles (e-textiles) hold great promise for serving as next-generation wearable electronics owing to their inherent flexible, air-permeable, and lightweight characteristics. However, these e-textiles are of limited performance mainly because of lacking powerful materials combination. Herein, a versatile e-textile through a simple, high-efficiency mixed-dimensional assembly of 2D MXene nanosheets and 1D silver nanowires (AgNWs) are presented. The effective complementary actions of MXene and AgNWs endow the e-textiles with superior integrated performances including self-powered pressure sensing, ultrafast joule heating, and highly efficient electromagnetic interference (EMI) shielding. The textile-based self-powered smart sensor systems obtained through the screen-printed assembly of MXene-based supercapacitor and pressure sensor are flexible and lightweight, showing ultrahigh specific capacitance (2390 mF cm-2 ), robust areal energy density (119.5 µWh cm-2 ), excellent sensitivity (474.8 kPa-1 ), and low detection limit (1 Pa). Furthermore, the interconnected conductive MXene/AgNWs network enables the e-textile with ultrafast temperature response (10.4 °C s-1 ) and outstanding EMI shielding effectiveness of ≈66.4 dB. Therefore, the proposed mixed-dimensional assembly design creates a multifunctional e-textile that offers a practical paradigm for next-generation smart flexible electronics.

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances.

Cancer remains the leading cause of death around the world. In cancer treatment, over 50% of cancer patients receive radiotherapy alone or in multimodal combinations with other therapies. One of the adverse consequences after radiation exposure is the occurrence of radiation-induced tissue fibrosis (RIF), which is characterized by the abnormal activation of myofibroblasts and the excessive accumulation of extracellular matrix. This phenotype can manifest in multiple organs, such as lung, skin, liver and kidney. In-depth studies on the mechanisms of radiation-induced fibrosis have shown that a variety of extracellular signals such as immune cells and abnormal release of cytokines, and intracellular signals such as cGAS/STING, oxidative stress response, metabolic reprogramming and proteasome pathway activation are involved in the activation of myofibroblasts. Tissue fibrosis is extremely harmful to patients' health and requires early diagnosis. In addition to traditional serum markers, histologic and imaging tests, the diagnostic potential of nuclear medicine techniques is emerging. Anti-inflammatory and antioxidant therapies are the traditional treatments for radiation-induced fibrosis. Recently, some promising therapeutic strategies have emerged, such as stem cell therapy and targeted therapies. However, incomplete knowledge of the mechanisms hinders the treatment of this disease. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of radiation-induced fibrosis.

Few-mode polymer waveguide amplifier with a dual-layer coronal refractive index profile.

A novel, to the best of our knowledge, few-mode waveguide amplifier with a dual-layer coronal core is first proposed. Reconfiguring the refractive index profile is adopted to equalize the modal gains pumped in a single mode. The polymer in terms of the prominent advantages of simple processing and the ease of adjusting refractive index is utilized. The waveguide supporting LP01, LP11a, and LP11b is optimized by the genetic algorithm and fabricated by accurate alignment mask. The crosstalk effect and modal profiles are characterized. The modal gains with different signal power and pumping modes are revealed. The schemes in forward and backward pumps are represented. An average gain of 11.84 dB per mode and an ultralow differential modal gain of 0.36 dB are obtained in a 0.3 cm waveguide at 1526 nm through backward pumping of the LP21b mode at 240 mW for an input signal power of 0.1 mW.

Removal of Tetracycline Hydrochloride by Photocatalysis Using Electrospun PAN Nanofibrous Membranes Coated with g-C3N4/Ti3C2/Ag3PO4.

In order to improve the photocatalytic performance of g-C3N4, the g-C3N4/Ti3C2/Ag3PO4 S-type heterojunction catalyst was prepared by electrostatic assembly method, and then the g-C3N4/Ti3C2/Ag3PO4/PAN composite nanofiber membrane was prepared by electrospinning technology. The morphology and chemical properties of the nanofiber membrane were characterized by SEM, FTIR, and XRD, and the photocatalytic degradation of tetracycline hydrochloride (TC) in water by the nanofiber membrane was investigated. The results showed that g-C3N4/Ti3C2/Ag3PO4 could be successfully loaded on PAN and uniformly distributed on the surface of composite nanofiber membrane by electrospinning technology. Increasing the amount of loading and catalyst, lowering the pH value and TC concentration of the system were conducive to the oxidation and degradation of TC. The nano-fiber catalytic membrane had been recycled five times and found to have excellent photocatalytic stability and reusability. The study of catalytic mechanism showed that h+, •OH and •O2- were produced and participated in the oxidation degradation reaction of TC, and •O2- plays a major role in catalysis. Therefore, this work provides a new insight into the construction of high-performance and high-stability photocatalytic system by electrospinning technology.

Rational reformation of Corynebacterium glutamicum for producing L-lysine by one-step fermentation from raw corn starch.

This article focuses on engineering Corynebacterium glutamicum to produce L-lysine efficiently from starch using combined method of "classical breeding" and "genome breeding." Firstly, a thermo-tolerable L-lysine-producing C. glutamicum strain KT45-6 was obtained after multi-round of acclimatization at high temperature. Then, amylolytic enzymes were introduced into strain KT45-6, and the resultant strains could use starch for cell growth and L-lysine production except the strain with expression of isoamylase. In addition, co-expression of amylolytic enzymes showed a good performance in starch degradation, cell growth and L-lysine production, especially co-expression of α-amylase (AA) and glucoamylase (GA). Moreover, L-lysine yield was increased by introducing AA-GA fusion protein (i.e., strain KT45-6S-5), and finally reached to 23.9 ± 2.3 g/L in CgXIIIPM-medium. It is the first report of an engineered L-lysine-producing strain with maximum starch utilization that may be used as workhorse for producing amino acid using starch as the main feedstock. KEY POINTS: • Thermo-tolerable C. glutamicum was obtained by temperature-induced adaptive evolution. • The fusion order between AA and GA affects the utilization efficiency of starch. • C. glutamicum with starch utilization was constructed by optimizing amylases expression.

Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933.

Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A-F (1-6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D-F (4-6) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey's method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure-activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to hα4ß2 was explained by molecular docking studies.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Objective: The accurate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) remains challenging. Few studies have investigated pathologic complete response (ypCR) prediction in patients with residual flat mucosal lesions after treatment. This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer (LARC). Methods: Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital. Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed, and a nomogram was constructed by incorporating the significant predictors. Results: Of the 246 patients with residual flat mucosal lesions included in the final analysis, 56 (22.8%) had ypCR. Univariate and multivariate analyses showed that pretreatment cT stage (pre-cT) ≤T2 (P=0.016), magnetic resonance tumor regression grade (MR-TRG) 1-3 (P=0.001) and residual mucosal lesion depth =0 mm (P<0.001) were associated with a higher rate of ypCR. A nomogram was developed with a concordance index (C-index) of 0.759 and the calibration curve showed that the nomogram model had good predictive consistency. The follow-up time ranged from 3.0 to 113.3 months, with a median follow-up time of 63.77 months. The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival (DFS) or overall survival (OS). Conclusions: Completely flat mucosa, early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT. Endoscopic mucosal re-evaluation before surgery is important, as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Transcription factor Sp1 is upregulated by PKCι to drive the expression of YAP1 during pancreatic carcinogenesis.

Recently, we identified that the atypical protein kinase C isoform ι (PKCι) enhances the expression of Yes-associated protein 1 (YAP1) to promote the tumorigenesis of pancreatic adenocarcinoma harboring mutant KRAS (mu-KRAS). To advance our understanding about underlying mechanisms, we analyze the transcription of YAP1 in pancreatic cancer cells and reveal that transcription factor specificity protein 1 (Sp1) is upregulated by PKCι and subsequently binds to multiple sites in YAP1 promoter to drive the transactivation of YAP1 in pancreatic cancer cells carrying mu-KRAS. The bioinformatics analysis further substantiates that the expression of PKCι, Sp1 and YAP1 is correlated and associated with the stages and prognosis of pancreatic tumors. Moreover, our apoptotic detection data demonstrate that combination of PKCι and Sp1 inhibitors at subtoxic doses displays synergistic effects on inducing apoptosis and reversing the immunosuppression of pancreatic cancer cells, establishing the combination of PKCι and Sp1 inhibitors as a promising novel therapeutic approach, or an adjuvant strategy to potentiate the antitumor effects of other immunotherapeutic agents in pancreatic cancer treatment.

An ultrahigh-throughput screening platform based on flow cytometric droplet sorting for mining novel enzymes from metagenomic libraries.

Uncultivable microbial communities provide enormous reservoirs of enzymes, but their experimental identification by functional metagenomics is challenging, mainly due to the difficulty of screening enormous metagenomic libraries. Here, we propose a reliable and convenient ultrahigh-throughput screening platform based on flow cytometric droplet sorting (FCDS). The FCDS platform employs water-in-oil-in-water double emulsion droplets serving as single-cell enzymatic micro-reactors and a commercially available flow cytometer, and it can efficiently isolate novel biocatalysts from metagenomic libraries by processing single cells as many as 108 per day. We demonstrated the power of this platform by screening a metagenomic library constructed from domestic running water samples. The FCDS assay screened 30 million micro-reactors in only 1 h, yielding a collection of esterase genes. Among these positive hits, Est WY was identified as a novel esterase with high catalytic efficiency and distinct evolutionary origin from other lipolytic enzymes. Our study manifests that the FCDS platform is a robust tool for functional metagenomics, with the potential to significantly improve the efficiency of exploring novel enzymes from nature.

Hepatic portal venous gas: A case report and analysis of 131 patients using PUBMED and MEDLINE database.

OBJECTIVE: Hepatic portal pneumatosis has a high mortality rate, and whether surgical intervention is necessary remains controversial. This experiment retrospectively analyzed the etiology, treatment methods and prognosis of adult patients with hepatoportal pneumocele to provide a theoretical basis for the treatment of this disease. METHODS: We analyzed the clinical symptoms and post-treatment of a 43-year-old male patient with HPVG admitted to hospital. We retrieved adult non-iatrogenic HPVG cases with complete clinical data in PUBMED,  and MEDLINE and other databases were retrieved for analysis, and summarized the pathogenesis, clinical symptoms, pathogenesis, pathogenesis and prognosis of different treatment schemes were summarized. RESULTS: The main etiology of HPVG are intestinal ischemia (27%), severe enteritis/intestinal perforation/intestinal fistula (16%), intestinal obstruction (7%), abdominal infection (7%), gastric diseases (11%), appendicitis and its complications (5%), acute hemorrhage or necrotizing pancreatitis (5%), Crohn's disease and its complications (4%), trauma (traffic accidents, falls) (2%), diverticulitis and perforation (6%), nephrogenic diseases (4%), spontaneous pneumohepatic portal vein (2%), other reasons (4%). And after analysis, we found that the survival rate of patients treated by surgery was 40.5% and the mortality rate was 19.1%, the difference between the two was significant. CONCLUSIONS: Etiology should be actively explored and surgical treatment is necessary.

[A Review of Progress of the Relation Between Stress Response and Diabetes Mellitus].

Stress response is an adaptive process of the organism to confront environmental perturbation. Moderate stress response induces the organism to establish effective adaptive strategies for survival, while excessive stress response results in stress injury, which is a major cause of a variety of physical or psychological diseases, including diabetes mellitus. Diabetes mellitus is a typical stress-related disease, with numerous evidence indicating that the development and progression of diabetes mellitus are closely related to stress response, such as metabolic stress, oxidative stress and endoplasmic reticulum stress. However, the detailed mechanisms of stress response mediated regulation of diabetes mellitus and how to prevent or treat diabetes mellitus via modification of stress response remain to be further investigated. Here, we will introduce the definition and regulatory mechanisms of stress response, as well as discuss the biological functions and mechanisms of various stress responses during the pathogenesis of diabetes mellitus. This review highlights recent advances of stress medicine associated with diabetes mellitus, in order to provide theoretical basis and reference for prevention and treatment of diabetes mellitus. Future studies should focus on elucidating the clinical application potential of the key factors of stress response that mediate the pathogenesis of diabetes mellitus, as well as boosting the related translational medicine studies.

Pain threshold, anxiety and other factors affect intensity of postoperative pain in gastric cancer patients: A prospective cohort study.

OBJECTIVE: This prospective cohort study explored factors related to postoperative pain in gastric cancer patients. METHODS: A total of 236 patients who underwent gastrectomy were enrolled. All patients enrolled in the study completed the Hospital Anxiety and Depression Scale (HADS) questionnaire and Life Orientation Test-Revised (LOT-R) questionnaire on the day before surgery. Heat pain threshold (HPT), cold pain threshold (CPT) and pressure pain threshold (PPT) were measured for all patients one day prior to surgery and demographic details were collected. All patients were connected to a patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery. The occurrence of postoperative pain was used as a dependent variable, and multivariate logistic regression analyses were conducted to screen for factors affecting postoperative pain. RESULTS: In total, 83 patients (35.2%) had postoperative pain. Body mass index (BMI) ≥28 kg/m2 [odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.07-6.67], total gastrectomy (OR: 2.64; 95% CI: 1.42-4.91), preoperative anxiety score ≥8 (OR: 2.37; 95% CI: 1.12-5.02), heat pain threshold ≤4.9 s (OR: 2.14; 95% CI: 1.06-4.32), pressure pain threshold ≤4 g (OR: 2.05; 95% CI: 1.05-4.03), and female gender (OR: 1.99; 95% CI: 1.04-3.83) were risk factors for postoperative pain. CONCLUSIONS: Obesity, wide range of gastrectomy, high preoperative anxiety, low HPT and PPT, and female gender are associated with increased risk for postoperative pain.

Exploring the mechanism of cisplatin resistance by transcriptome sequencing and reversing the chemoresistance by autophagy inhibition in small cell lung cancer.

Cisplatin plays a key role in treating small cell lung cancer (SCLC); however, the rapid development of cisplatin resistance limits its treatment effect. The detailed mechanisms of cisplatin-resistance, particularly in SCLC, remain unclear. We analyzed the differentially expressed genes (DEGs) between cisplatin-resistant small cell lung cancer cell line H446/CDDP and its parental cell line H446, using the transcriptome sequencing technique. Gene ontology (GO) analysis and the subsequent tests demonstrated that the functions of protein ubiquitination and autophagy are more active in the H446/CDDP cells. Autophagy plays a protective role in the H446/CDDP cells by using the autophagy inhibitors, 3-methyladenine and bafilomycin A1. Moreover, antimalarial drugs that inhibit autophagy by increasing the pH of lysosomes can also enhance cisplatin-induced cell death.

Highly effective antibacterial zeolitic imidazolate framework-67/alginate fibers.

Antibacterial fibers have great potential in many applications including wound dressings, surgical gowns, and surgical sutures, and play an important role in our daily life. However, the traditional fabrication method for the antibacterial fibers shows high cost, complexity, and inferior antibacterial durability. Herein, we report a facile and scalable fabrication of highly effective antibacterial alginate (SA) composite fibers through blend spinning of zeolitic imidazolate framework-67 (ZIF-67) particles and SA. The fabricated ZIF-67@SA composite fibers show high tensile strength and initial modulus. More importantly, the ZIF-67@SA composite fibers demonstrate excellent antibacterial properties, and the antibacterial efficiency reaches over 99% at ultralow ZIF-67 loading (0.05 wt%). In addition, the ZIF-67@SA fibers show good antibacterial durability even after five laundering cycles. The excellent antibacterial performance of the ZIF-67@SA fibers is attributed to the synergistic effects of the highly effective antibacterial ZIF-67 particles, swelling of alginate, and immobilization of ZIF-67 particles both inside and outside the fiber surface. This work may shed light on the antibacterial mechanism of metal organic frameworks and pave the way for the development of high-performance antibacterial textiles.

Laparoscopy combining with ureteroscopy for horseshoe kidney accompanying with duplicate kidney and a ureteral calculus: a case report.

BACKGROUND: Horseshoe kidney (HSK) is a common renal fusion anomaly, occurring in about 1 in 400-600 individuals. In addition, the incidence of duplicated collecting system is about 0.8%. CASE PRESENTATION: This report documents an extremely rare case, which was treated by multiple procedures in the same operative session to accomplish laparoscopic amputation of the HSK isthmus, resection of duplicate kidney and ureteroscopic lithotripsy. CONCLUSION: Results showed that minimally invasive surgery with use of multiple endoscopes may be a feasible choice for this patient population with complicated comorbid renal conditions.