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.

Application value of extreme flexion and abduction hip combined with stirrup-shaped multifunctional leg frame in blocking obturator nerve reflex in transurethral resection of bladder tumor.

OBJECTIVE: To explore the effectiveness and safety of the extreme flexion and abduction hip combined with a stirrup-shaped multifunctional leg frame position in preventing obturator nerve reflex during plasma resection of bladder tumors (TUR-BT). METHODS: A total of 112 patients with bladder tumors were included in the study. The control group was placed in a lithotomy position, while the experimental group was placed in an extreme flexion and abduction hip combined with a stirrup-shaped multifunctional leg frame position. The grade of leg jerking, operation time, and some operative complications were compared between groups. RESULTS: The operation time, bleeding volume, the grade of leg jerking, second TUR-BT, and acquisition of detrusor muscle were significantly better in the experimental group compared to the control group (P = 0.018, P = 0.013, P < 0.001, P = 0.041, and P < 0.001, respectively). The grade of leg jerking in the experimental group was extremely low (distributed in grade 1 and 2), and there were no severe reactions in grade 3 and 4. CONCLUSION: The extreme flexion and abduction hip combined with a stirrup-shaped multifunctional leg frame position for TUR-BT is a safe and effective treatment method that can effectively prevent obturator nerve reflex, reduce complications, improve surgical efficacy, and reduce anesthesia dependence and risk.

Enhanced cavitation dose and reactive oxygen species production in microbubble-mediated sonodynamic therapy for inhibition of Escherichia coli and biofilm.

Sonodynamic therapy (SDT) is an emerging antibacterial therapy. This work selected hematoporphyrin monomethyl ether (HMME) as the sonosensitizer, and studied the enhanced inhibition effect of Escherichia coli and biofilm by microbubble-mediated cavitation in SDT. Firstly, the influence of microbubble-mediated cavitation effect on different concentrations of HMME (10 µg/ml, 30 µg/ml, 50 µg/ml) was studied. Using 1,3-diphenylisobenzofuran (DPBF) as an indicator, the effect of microbubble-mediated cavitation on the production of reactive oxygen species (ROS) was studied by absorption spectroscopy. Secondly, using agar medium, laser confocal microscopy and scanning electron microscopy, the effect of microbubble-mediated cavitation on the activity and morphology of bacteria was studied. Finally, the inhibitory effect of cavitation combined with SDT on biofilm was evaluated by laser confocal microscopy. The research results indicate that: (1) Microbubble-mediated ultrasound cavitation can significantly increase cavitation intensity and production of ROS. (2) Microbubble-mediated acoustic cavitation can alter the morphological structure of bacteria. (3) It can significantly enhance the inhibition of SDT on the activity of Escherichia coli and its biofilm. Compared with the control group, the addition of microbubbles resulted in an increase in the number of dead bacteria by 61.7 %, 71.6 %, and 76.2 %, respectively. The fluorescence intensity of the biofilm decreased by 27.1 %, 80.3 %, and 98.2 %, respectively. On the basis of adding microbubbles to ensure antibacterial and biofilm inhibition effects, this work studied the influence of cavitation effect in SDT on bacterial structure, providing a foundation for further revealing the intrinsic mechanism of SDT.

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.

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.

Development of a new cerebral ischemia reperfusion model of Mongolian gerbils and standardized evaluation system.

BACKGROUND: The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis. However, the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle. Additionally, the lack of an evaluation system for the cerebral ischemia/reperfusion (I/R) model of gerbils has shackled the application of this model. METHODS: We created a symptom-oriented principle and detailed neurobehavioral scoring criteria. At different time points of reperfusion, we analyzed the alteration in locomotion by rotarod test and grip force score, infarct volume by triphenyltetrazolium chloride (TTC) staining, neuron loss using Nissl staining, and histological characteristics using hematoxylin-eosin (H&E) straining. RESULTS: With a successful model rate of 56%, 32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury, and the mortality rate in the male gerbils was significantly higher than that in the female gerbils. The successfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion; formed obvious infarction; exhibited typical pathological features, such as tissue edema, neuronal atrophy and death, and vacuolated structures; and were partially recovered with the extension of reperfusion time. CONCLUSION: This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model, which could provide a new cerebral I/R model of gerbils with more practical applications.

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.

G6PD Maintains Redox Homeostasis and Biosynthesis in LKB1-Deficient KRAS-Driven Lung Cancer.

Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NAPDH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer model, we show that ablation of G6PD significantly suppresses KrasG12D/+;Lkb1-/- (KL) but not KrasG12D/+;p53-/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics revealed that G6PD ablation significantly impaired NADPH generation, redox balance and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation caused p53 activation that suppressed tumor growth. As tumor progressed, G6PD-deficient KL tumors increased an alternative NADPH source, serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations.

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.

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.

Extracorporeal membrane oxygenation in immunocompromised patients with acute respiratory failure: A retrospective cohort study.

BACKGROUND: The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure. METHODS: This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed. RESULTS: The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/µL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34-2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14-1.61, p = 0.003) were identified as independent risk factors for mortality. CONCLUSIONS: In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.

Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a major clinical challenge. Periplocin, a major bioactive component of the traditional Chinese herb Cortex periplocae, has recently been reported to be a potential anticancer drug. However, the mechanism of action is poorly understood. Here, we show that periplocin exhibits promising anticancer activity against CRC both in vitro and in vivo. Mechanistically, periplocin promotes lysosomal damage and induces apoptosis in CRC cells. Notably, periplocin upregulates LGALS3 (galectin 3) by binding and preventing LGALS3 from Lys210 ubiquitination-mediated proteasomal degradation, leading to the induction of excessive lysophagy and resultant exacerbation of lysosomal damage. Inhibition of LGALS3-mediated lysophagy attenuates periplocin-induced lysosomal damage and growth inhibition in CRC cells, suggesting a critical role of lysophagy in the anticancer effects of periplocin. Taken together, our results reveal a novel link between periplocin and the lysophagy machinery, and indicate periplocin as a potential therapeutic option for the treatment of CRC.Abbreviations: 3-MA: 3-methyladenine; ACACA/ACC1: acetyl-CoA carboxylase alpha; AMPK: adenosine monophosphate-activated protein kinase; AO: Acridine orange; ATG5: autophagy related 5; ATG7: autophagy related 7; CALM: calmodulin; CHX: cycloheximide; CRC: colorectal cancer; CQ: chloroquine; CTSB: cathepsin B; CTSD: cathepsin D; ESCRT: endosomal sorting complex required for transport; LAMP1: lysosomal associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MKI67/Ki-67: marker of proliferation Ki-67; MTOR: mechanistic target of rapamycin kinase; P2RX4/P2X4: purinergic receptor P2X 4; PARP1/PARP: poly(ADP-ribose) polymerase 1; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TRIM16: tripartite motif containing 16.

Investigation of In Situ Vibration During Wire and Arc Additive Manufacturing.

Wire and arc additive manufacturing (WAAM) is becoming a promising technique due to its high deposition rate and low cost. However, WAAM faces challenges of coarse grains. In this study, a novel in situ vibration method was proposed to suppress these imperfections of WAAM. Temperature and vibration distributions were explored first, and the optimized parameters were utilized for manufacturing low-carbon steel parts. The results revealed that after the vibration, the average grain size in fine grain zone was reduced from 9.8 to 7.1 µm, and that in coarse grain zone was declined from 10.6 to 7.4 µm, respectively. No large deformation occurred due to the low temperature. Grain refining was attributed to more dendrite fragments induced by excessive stress at the roots of dendrites. The refined grains enhanced mechanical strength of the parts in both X and Z directions and improved the average hardness. After the vibration, the ultimate tensile strength and yield strength were increased to 522.5 and 395 MPa, which represented an increase of 10% and 13.8%, respectively. The average hardness was improved to 163 HV, which was an increase of 10.1%.

Acid and alkali-resistant fabric-based triboelectric nanogenerator for self-powered intelligent monitoring of protective clothing in highly corrosive environments.

The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common. Here, we demonstrate a chemical-resistant triboelectric nanogenerator (CR-TENG) based on polysulfonamide (PSA) and polytetrafluoroethylene (PTFE) non-woven fabrics. The CR-TENG can stably harvest biological motion energy and perform intelligent safety protection monitoring in a strong corrosive environment. After treatment with strong acid and alkali solution for 7 days, the fabric morphology, diameter, tensile properties and output of CR-TENG are not affected, showing high reliability. CR-TENG integrated into protective equipment can detect the working status of protective equipment in real time, monitor whether it is damaged, and provide protection for wearers working in high-risk situations. In addition, the nonwoven-based CR-TENG has better wearing comfort and is promising for self-powered sensing in harsh environments.

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.

Short Peptide Nanofiber Biomaterials Ameliorate Local Hemostatic Capacity of Surgical Materials and Intraoperative Hemostatic Applications in Clinics.

Short designer self-assembling peptide (dSAP) biomaterials are a new addition to the hemostat group. It may provide a diverse and robust toolbox for surgeons to integrate wound microenvironment with much safer and stronger hemostatic capacity than conventional materials and hemostatic agents. Especially in noncompressible torso hemorrhage (NCTH), diffuse mucosal surface bleeding, and internal medical bleeding (IMB), with respect to the optimal hemostatic formulation, dSAP biomaterials are the ingenious nanofiber alternatives to make bioactive neural scaffold, nasal packing, large mucosal surface coverage in gastrointestinal surgery (esophagus, gastric lesion, duodenum, and lower digestive tract), epicardiac cell-delivery carrier, transparent matrix barrier, and so on. Herein, in multiple surgical specialties, dSAP-biomaterial-based nano-hemostats achieve safe, effective, and immediate hemostasis, facile wound healing, and potentially reduce the risks in delayed bleeding, rebleeding, post-operative bleeding, or related complications. The biosafety in vivo, bleeding indications, tissue-sealing quality, surgical feasibility, and local usability are addressed comprehensively and sequentially and pursued to develop useful surgical techniques with better hemostatic performance. Here, the state of the art and all-round advancements of nano-hemostatic approaches in surgery are provided. Relevant critical insights will inspire exciting investigations on peptide nanotechnology, next-generation biomaterials, and better promising prospects in clinics.

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.

Identification of Typical Ecosystem Types by Integrating Active and Passive Time Series Data of the Guangdong-Hong Kong-Macao Greater Bay Area, China.

The identification of ecosystem types is important in ecological environmental assessment. However, due to cloud and rain and complex land cover characteristics, commonly used ecosystem identification methods have always lacked accuracy in subtropical urban agglomerations. In this study, China's Guangdong-Hong Kong-Macao Greater Bay Area (GBA) was taken as a study area, and the Sentinel-1 and Sentinel-2 data were used as the fusion of active and passive remote sensing data with time series data to distinguish typical ecosystem types in subtropical urban agglomerations. Our results showed the following: (1) The importance of different features varies widely in different types of ecosystems. For grassland and arable land, two specific texture features (VV_dvar and VH_diss) are most important; in forest and mangrove areas, synthetic-aperture radar (SAR) data for the months of October and September are most important. (2) The use of active time series remote sensing data can significantly improve the classification accuracy by 3.33%, while passive time series remote sensing data improves by 4.76%. When they are integrated, accuracy is further improved, reaching a level of 84.29%. (3) Time series passive data (NDVI) serve best to distinguish grassland from arable land, while time series active data (SAR data) are best able to distinguish mangrove from forest. The integration of active and passive time series data also improves precision in distinguishing vegetation ecosystem types, such as forest, mangrove, arable land, and, especially, grassland, where the accuracy increased by 21.88%. By obtaining real-time and more accurate land cover type change information, this study could better serve regional change detection and ecosystem service function assessment at different scales, thereby supporting decision makers in urban agglomerations.

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.

Long-term follow-up of HER2 overexpression in patients with rectal cancer after preoperative radiotherapy: A prospective cohort study.

BACKGROUND: The role of HER2 overexpression in rectal cancer is controversial. AIM: To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer. METHODS: Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected. A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy, followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients' HER2 expression status. Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed. Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status, and the differences between groups were verified using the log-rank test. RESULTS: A total of 151 patients were enrolled in this study. A total of 27 (17.9%) patients were ultimately confirmed to be HER2-positive. The follow-up duration ranged from 9 mo to 210 mo, with a median of 134 mo. Distant metastasis and local recurrence occurred in 60 (39.7%) and 24 (15.9%) patients, respectively. HER2 positivity was significantly associated with the pre-treatment lymph node stage (pre-N) (P = 0.040), while there were no differences between HER2 status and age, sex, preoperative CEA levels (pre-CEA), T stage, and lympho-vascular invasion. In terms of prognosis, HER2 overexpression was correlated with distant metastasis (P = 0.002) rather than local recurrence (P > 0.05). The multivariate analysis demonstrated that elevated pre-CEA [P = 0.002, odds ratio (OR) = 3.277, 97.5% confidence interval (CI): 1.543-7.163], post N(+) (P = 0.022, OR = 2.437, 97.5%CI: 1.143-5.308) and HER2(+) (P = 0.003, OR = 4.222, 97.5%CI: 1.667-11.409) were risk factors for distant metastasis. The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival (DFS) [hazard ratio: 1.69 (95%CI: 0.91-3.14); P = 0.048] and overall survival (OS) [1.95 (1.05-3.63); P = 0.0077]. CONCLUSION: HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis, which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.