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In this study, we introduce an innovative photoacoustic frequency shift (PAFS) technique for hydrogen (H2) detection, complemented by both theoretical models and practical experiments. To mitigate cross-sensitivity, we analyzed the sound speeds of six different gases, confirming minimal interference with H2 due to significant velocity disparities. Central to our approach is the design of a miniaturized step-added T-type Photoacoustic Cell (PAC), with parameters meticulously optimized for enhanced performance. Using COMSOL Multiphysics' Thermal Viscous Acoustics module, we conducted simulations to evaluate the quality factor and acoustic pressure, both crucial for the sensor's efficiency. Additionally, we assessed the system's stability, influenced by gas flow, through gas velocity distribution analyses using the Computational Fluid Dynamics module. Experimental investigations focused on the system's sensing performance, revealing a distinct frequency shift of âˆ¼45 Hz for every 1 % change in H2 concentration, with a high linear correlation (R2 = 0.99825). The system's response and recovery times were measured at 1.09 s and 1.25 s, respectively. Long-term stability, evaluated over 3000 s using Allan deviation, indicated a minimum detection limit (MDL) of 102.47 ppm at an integration time of 375 s. These findings validate the efficacy of the step-added T-type PAC in H2 detection.

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Peptides and proteins undergo crucial modifications to alter their physicochemical properties to expand their applications in diverse fields. Various techniques, such as unnatural amino acid incorporation, enzyme catalysis, and chemoselective methods, have been employed for site-selective peptide and protein modification. While traditional methods remain valuable, advancement in host-guest chemistry introduces innovative and promising approaches for the selective modification of peptides and proteins. Macrocycles exhibit robust binding affinities, particularly with natural amino acids, which facilitates their use in selectively binding to specific sequences. This distinctive property endows macrocycles with the potential for modification of target peptides and proteins. This review provides a comprehensive overview of strategies utilizing macrocycles for the selective modification of peptides and proteins. These strategies unlock new possibilities for constructing antibody-drug conjugates and stabilizing volatile medications.

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Myocardial fibrosis (MF) is involved in hypertension, myocardial infarction and heart failure. It has been reported that circular RNA (circRNA) is a key regulatory factor of MF progression. In this study, we revealed that circ_0002295 and CXCR2 were elevated, and miR-1287 was reduced in MF patients. Knockdown of circ_0002295 effectively suppressed the proliferation, migration and MF progression. Circ_0002295 was the molecular sponge of miR-12878, and miR-1287 inhibitor reversed the biological functions of circ_0002295 on the myocardial fibrosis. CXCR2 was a target gene of miR-1287, and CXCR2 silencing relieved the impacts of miR-1287 inhibitor on cardiac myofibroblasts. Circ_0002295 promoted MF progression by regulating the miR-1287/CXCR2 axis, providing a possible circRNA-targeted therapy for MF.

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MicroRNAs (miRNAs) play an important biomarker in various biological processes, especially cancer related, yet economic, simple, sensitive and specific methods for miRNA determination are still challenging. In this study, we have developed stepwise-strand displacement amplification (S-SDA)-based colorimetric sensing platform for let-7a miRNA detection in clinical serum samples. Our results demonstrated that the developed S-SDA-based method shows high sensitivity with a detection limit of 63.2 pM and a naked eye detection limit of 0.1 nM. Moreover, the S-SDA amplifier is able to discriminate target miRNAs from their mutants with high accuracy and specificity. With its high sensitivity and selectivity, this method successfully identified healthy individuals from patients with colon cancer by detecting let-7a miRNAs in serum. We believe the colorimetric analysis method will provide a new paradigm for the detection of miRNA with different abundance and show great potential for clinical application in biomedical analysis and early clinical diagnosis.

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Highly sensitive and stable measurement of methane (CH4) and acetylene (C2H2) based on a novel dual-channel off-beam quartz-enhanced photoacoustic spectroscopy and time-division multiplexing technique was realized by a compact 3D-printed gas cell with a size of 3 × 2 × 1 cm3. Two near-infrared distributed feedback diode lasers were employed to target the CH4 absorption line at 6046.9 cm-1 and the C2H2 absorption line at 6521.2 cm-1, respectively. Second-harmonic wavelength modulation spectroscopy method was used for photoacoustic signal recovery. A minimum detection level of âˆ¼ 7.63 parts-per-million in volume (ppmv) for CH4 and a level of âˆ¼ 17.47 ppmv for C2H2 were achieved with a 1 s lock-in integration time, leading to a normalized noise equivalent absorption (NNEA) coefficient of 7.24 × 10-8 cm-1·W·Hz-1 and 3.73 × 10-8 cm-1·W·Hz-1 for CH4 and C2H2, respectively. Allan-Werle deviation analysis was employed to evaluate the stability and the minimum detection limit (MDL) of the developed photoacoustic CH4/C2H2 dual-gas photoacoustic sensor. Owing to the high stability of the developed sensor system, an MDL of âˆ¼ 0.73 ppmv and an MDL of âˆ¼ 1.60 ppmv with a 100 s averaging time were achieved for CH4 and C2H2, respectively.

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To realize early fire identification in cotton harvesting operations, a mid-infrared carbon monoxide (CO) sensor system was developed. To match the broadband light source with a 15° divergence angle, a multipass gas cell (MPGC) with an effective path length of 180 cm was designed to improve sensor sensitivity, leading to a limit of detection (LoD) of 0.83 parts-per-million by volume (ppmv). A damping module with springs at the bottom and front/back sides was fabricated, which can effectively reduce the vibration intensity by >80%. The sensor system can operate normally from -40 °C to 85 °C by stabilizing the temperature of the optical module through heating or cooling as well as using automotive electronic components. An adaptive early fire identification algorithm based on a dual-parameter threshold alarming method was proposed to avoid false and missing alarms. Field deployments on a harvester verified the good practicability of the sensor system.

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Background: The Hippo pathway is an essential signaling cascade that regulates cell and organ growth. However, there is no consensus about (i) the expression levels of the Hippo signaling core components yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in lung cancer, especially in small cell lung cancer (SCLC), or (ii) their association with the prognosis of patients with SCLC. Methods: We screened relevant articles and identified eligible studies in the PubMed, EMBASE, COCHRANE, and WanFang databases. A combined analysis was performed to investigate (i) the expression levels of the major effectors, YAP and TAZ, in lung cancer and its subsets and (ii) their prognostic role in lung cancer, especially in SCLC. Results: In total, 6 studies related to TAZ and 13 studies concerning YAP were enrolled in this meta-analysis. We found that high TAZ expression was significantly associated with poor overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in the overall population [P h < 0.001, crude hazard ratio (HR) = 1.629, 95% CI = 1.199-2.214 for TAZ expression; P h = 0.029, adjusted HR = 2.127, 95% CI = 1.307-3.460 for TAZ], the Caucasian population (P h = 0.043, crude HR = 1.233, 95% CI = 1.030-1.477 for TAZ expression), and the Asian population (P h = 0.551, adjusted HR = 2.676, 95% CI = 1.798-3.982 for TAZ). Moreover, there was a significant negative association between YAP expression and an unsatisfactory survival of patients with lung cancer (P h = 0.327, crude HR = 1.652, 95% CI = 1.211-2.253 for YAP expression) and patients with NSCLC [disease-free survival (DFS): Ph = 0.693, crude HR = 2.562, 95% CI = 1.876-3.499 for YAP expression; Ph = 0.920, crude HR = 2.617, 95% CI = 1.690-4.052 for YAP-mRNA; OS: Ph = 0.878, crude HR = 1.777, 95% CI = 1.233-2.562 for YAP expression], especially in the Asian population (DFS: P h = 0.414, crude HR = 2.515, 95% CI = 1.755-3.063; OS: P h = 0.712, crude HR = 1.772, 95% CI = 1.214-2.587). However, no association was observed in the multivariate combined analysis. High YAP expression was significantly associated with short OS of patients with SCLC in our combined multivariate analysis in the Asian population (P h = 0.289, crude HR = 4.482, 95% CI = 2.182-9.209), but not with crude data (P h = 0.033, crude HR = 1.654, 95% CI = 0.434-6.300). Conclusion: The Hippo pathway is involved in carcinogenesis and progression of NSCLC and SCLC, and high expression levels of YAP and TAZ are independent and novel prognostic factors for lung cancer.

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In order to realize early fire detection and location, a mid-infrared carbon monoxide (CO) and carbon dioxide (CO2) dual-gas sensor system was developed, which mainly includes a gas pretreatment module, a CO2 sensor module, a CO sensor module, and a laptop monitoring platform. CO2 and CO absorption lines located at 4.26 µm and 4.66 µm, respectively, were selected to ensure good selectivity of the sensor system. A series of experiments were carried out to evaluate the sensor performance. The 10-90% response time of the CO and CO2 sensor modules was measured to be âˆ¼ 30 s at a flow rate of 1 L/min, and the limits of detection (LoD) of CO2 and CO were assessed to be 5.66 parts per million by volume (ppmv) and 0.94 ppmv, respectively, when the averaging time was 0.25 s. According to the correlation between CO2 and CO concentration in the early fire stage, a method of early fire detection was studied and proposed using the normalized concentration ratio between CO and CO2 (C(CO)/C(CO2)) as the key alarm parameter. Based on gas turbulent diffusion (GTD) model combined with particle swarm optimization (PSO) algorithm, a mobile early fire location method was presented. Correlative experiment results verified that the reported sensor system has a good performance for early fire detection and location.

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BACKGROUND: Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance. METHODS: Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo. RESULTS: We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdown CrkL expression suppressed PI3K/Akt/MRP1 signaling, which indicated CrkL siRNA reversed doxorubicin effect through regulating PI3K/Akt/MRP1 pathway. In addition, overexpression of MRP1 could evidently reduce apoptosis rate and reversed the inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells. Finally, in vivo experiments revealed that CrkL silencing acted a tumor-suppressing role in myelogenous leukemia via regulating PI3K/Akt/MRP1 signaling. CONCLUSION: Together, we indicated that CrkL is up-regulated in myelogenous leukemia cells and silencing of CrkL could reverse Doxorubicin resistance effectively. These results show a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy.

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Three-dimensional (3D) reconstruction and measurement are popular techniques in precision manufacturing processes. In this manuscript, a single image 3D reconstruction method is proposed based on a novel monocular vision system, which includes a three-level charge coupled device (3-CCD) camera and a ring structured multi-color light emitting diode (LED) illumination. Firstly, a procedure for the calibration of the illumination's parameters, including LEDs' mounted angles, distribution density and incident angles, is proposed. Secondly, the incident light information, the color distribution information and gray level information are extracted from the acquired image, and the 3D reconstruction model is built based on the camera imaging model. Thirdly, the surface height information of the detected object within the field of view is computed based on the built model. The proposed method aims at solving the uncertainty and the slow convergence issues arising in 3D surface topography reconstruction using current shape-from-shading (SFS) methods. Three-dimensional reconstruction experimental tests are carried out on convex, concave, angular surfaces and on a mobile subscriber identification module (SIM) card slot, showing relative errors less than 3.6%, respectively. Advantages of the proposed method include a reduced time for 3D surface reconstruction compared to other methods, demonstrating good suitability of the proposed method in reconstructing surface 3D morphology.

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In order to improve the performance of the large divergence angle mid-infrared source in gas sensing, this paper aims at developing a methane (CH4) sensor with non-dispersive infrared (NDIR) technology using a compact pentahedron gas-cell. A paraboloid concentrator, two biconvex lenses and five planar mirrors were used to set up the pentahedron structure. The gas cell is endowed with a 170 mm optical path length with a volume of 19.8 mL. The mathematical model of the cross-section and the three-dimension spiral structure of the pentahedron gas-cell were established. The gas-cell was integrated with a mid-infrared light source and a detector as the optical part of the sensor. Concerning the electrical part, a STM32F429 was employed as a microcontroller to generate the driving signal for the IR source, and the signal from the detector was sampled by an analog-to-digital converter. A static volumetric method was employed for the experimental setup, and 20 different concentration CH4 samples were prepared to study the sensor's evaluation, which revealed a 1σ detection limit of 2.96 parts-per-million (ppm) with a 43 s averaging time.

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System-level integration of a midinfrared carbon dioxide (CO2) sensor system based on tunable laser absorption spectroscopy (TLAS) was realized for the analysis of dissolved CO2 in seawater, employing an interband cascade laser (ICL) centered at 4319 nm and a multipass cell (MPC) with an optical path length of 29.8 m. At a low measurement pressure of 30 Torr, three absorption lines of 12CO2 were selected to realize different measurement ranges and a 13CO2 absorption line was targeted for simultaneous isotopic abundance analysis of δ13CO2. The sensor system was compactly integrated into a standalone system with automatic operation for underwater field deployment, and the working process was controlled by a specially designed electrical system. A gas-liquid separator system was developed for CO2 extraction from water, and a pressure-control mechanism with two operation modes (i.e., static and dynamic modes) was proposed to make the sensor system applicable under a deep-sea environment. A series of experiments were carried out in the laboratory for performance assessment of the developed sensor system employed for the analysis of dissolved CO2 in water. The sensor was deployed for a field test for natural gas hydrates exploration at an underwater depth of 0-2000 m in the South China Sea, with the sensor operating normally during the deployment.

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Rationale: The circadian clock coordinates cell proliferation and metabolism and impacts the progression of some diseases, particularly cancer. Pharmacological modulation of the circadian machinery may be an effective therapeutic approach for treating cancer. SR9009 is a specific synthetic agonist of the REV-ERBs, essential circadian clock components. However, the potential efficacy and antitumor mechanism of this drug in small-cell lung cancer (SCLC) remains poorly understood. Methods: Here, we used chemosensitive cells (H69 and H446) and the corresponding chemoresistant cells (H69AR and H446DDP) to assess the efficacy of the REV-ERB agonist SR9009 for the treatment of SCLC in vitro and further validated the antitumor effect in subcutaneous tumor models of SCLC. Then, we determined whether REV-ERBα was correlated with the anti-SCLC effect of SR9009. Chromatin immunoprecipitation (ChIP) sequencing assays were conducted to identify potential DNA sequences directly regulated by REV-ERBα. Autophagy regulation by REV-ERBα and its possible mechanism in SR9009-based SCLC therapy were analyzed. Results: Here, we showed that the REV-ERB agonist SR9009 is specifically lethal to both chemosensitive and chemoresistant SCLC cells. REV-ERBα was involved in the antitumor effect of SR9009 in SCLC. The core autophagy gene Atg5 was identified as a direct downstream target of REV-ERBα and was suppressed by the REV-ERB agonist SR9009 in SCLC. Furthermore, the interaction of REV-ERBα with this autophagy gene impaired autophagy activity, leading to SR9009 cytotoxicity in SCLC cells. Principal conclusions: Our study provided a novel viewpoint indicating that the REV-ERB agonist SR9009 could be a novel and promising therapeutic strategy in first- or second-line SCLC treatment. The anti-SCLC effect of SR9009 is mediated by REV-ERB dependent suppression of autophagy via direct repression of the autophagy gene Atg5.

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BACKGROUND: The hepatic microenvironment, which may include chronic inflammation and fibrosis, is considered to contribute to the development of liver metastases. Hepatic steatosis (HS) might cause liver inflammation and fibrosis. However, to date, no studies have investigated the impact of HS on liver metastasis in patients with non-small cell lung cancer (NSCLC). METHODS: A retrospective cohort study was performed on patients who received NSCLC treatment at two hospitals affiliated with the Southern Medical University from January 2005 to December 2015. The patients were grouped according to the presence of HS. The clinicopathological features of patients between the two groups were compared. The effect of HS on liver metastasis and overall metastasis was evaluated, adjusting for other confounders using Cox regression analyses. RESULTS: In total, 1,873 patients with NSCLC with no distant metastases were included in this study, and 408 (21.8%) patients were diagnosed with HS (at the time of diagnosis or before diagnosis). Liver metastases occurred in 166 (8.9%) patients. Liver metastasis-free survival was significantly worse in the study (HS) group (hazard ratio (HR) 1.42; (95% CI [1.03-1.96]); P = 0.031). Multivariate regression analysis demonstrated that HS was an independent risk factor for liver metastasis (HR 1.43; 95% CI [1.02-2.01]; P = 0.039). However, HS was not associated with overall metastasis of NSCLC (HR 0.99; 95% CI [0.84-1.17]; P = 0.895). CONCLUSION: Hepatic steatosis was an independent predictor of liver metastasis from in patients with NSCLC.

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BACKGROUND: The impact of hepatitis B virus (HBV) infection status on liver metastasis of nasopharyngeal carcinoma (NPC) has not been thoroughly elucidated to date. This study aimed to determine how HBV infection status influences liver metastasis of NPC through the analysis of clinical samples. METHODS: A total of 1,367 patients with pathologically diagnosed NPC who received systemic treatment at Nanfang Hospital or Zhujiang Hospital between January 2005 and December 2015 were enrolled in this retrospective study. Based on their HBV infection status, these patients were separated into four groups: negative infection (n=492), chronic HBV infection (n=123), inactive HBV carrier (n=175), and resolved HBV infection (n=577). The relationship between HBV infection status and liver metastasis of NPC was examined. RESULTS: Compared with the negative infection group, we observed that an inactive HBV carrier status was related to liver metastasis in patients with NPC (HR: 0.392; 95% CI: 0.178-0.863; P=0.020). The resolved HBV infection group had a lower risk of liver metastasis than the negative infection group (HR: 0.621; 95% CI: 0.402-0.959; P=0.032). There was no direct association between HBV infection status and distant metastasis of NPC. CONCLUSIONS: Inactive HBV infections and resolved HBV infections are highly associated with a decreased risk of liver metastases in NPC patients compared with patients without HBV infections.

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A mid-infrared cavity-enhanced sensor system was demonstrated for the detection of formaldehyde (H2CO) using a continuous-wave (cw) interband cascade laser (ICL) centered at 3599 nm. A compact Fabry-Perot (F-P) cavity with a physical size of 38 × 52 × 76 mm3 was developed consisting of two concave mirrors with a radius of curvature of 80 mm and a reflectivity of 99.8% at 3.6 µm. Different from the widely reported electro-optical (EO) external modulation based Pound-Drever-Hall (PDH) locking technique, a radio-frequency electrical internal modulation based PDH technique was used for locking the laser mode to the cavity mode. A dual-feedback control on the laser current and on the piezo transducer (PZT) displacement was utilized for further stabilizing mode locking. A 20 m effective optical path length was achieved with a cavity length of 2 cm and a finesse of 1572. The effectiveness and sensitivity of the sensor system were demonstrated by targeting an absorption line at 2778.5 cm-1 for H2CO measurements. A linear relation between the cavity transmitted signal amplitude and the H2CO concentration was obtained within the range of 0-5 ppm. A 1σ detection limit of 25 parts-per-billion (ppb) was achieved with an averaging time of 1 s based on Allan-Werle variance analysis. The reported dual-feedback RF modulation based PDH technique led to a method for gas detection using a similar experimental setup and measurement scheme.

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Design and fabrication of a dual spot-ring Herriott cell (DSR-HC) were proposed. The sealed Herriott cell with a dimensional size of 5.5 cm × 9.2 cm × 32.1 cm, possessed two input/output coupling holes leading to two absorption path lengths of ~20 m and ~6 m, respectively. An acetylene (C2H2) sensor system with a double-range was developed using the DSR-HC and wavelength modulation spectroscopy (WMS) technique. A near-infrared distributed feedback (DFB) laser was employed for targeting a C2H2 absorption line at 6521.2 cm-1. C2H2 concentration measurements were carried out by modulating the laser at a 5 kHz frequency and demodulating the detector signal with LabVIEW software. An Allan-Werle deviation analysis indicated that the limit of detection (LoD) for the two absorption path lengths of 20 m and 6 m are 7.9 parts-per-million in volume (ppmv) and 4.0 ppmv, respectively. The DSR-HC concept can be used to fabricate similar cells for single-gas detection requiring two different detection ranges as well as for dual-gas detection requiring different absorption path lengths.

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Correlation analysis of red blood cell distribution width (RDW) and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-10 in rheumatoid arthritis (RA) to investigate whether RDW can serve as a potential parameter for indicating inflammation in RA patients. A total of 670 RA patients from October 2014 to April 2016 were enrolled in our study. The white blood cell (WBC), red blood cell (RBC), platelet (PLT), hemoglobin (HGB), RDW, CRP, and ESR in peripheral blood of patients with RA were retrospectively analyzed. The relative expression of TNF-α, IL-6, and IL-10 was detected by RT-qPCR. Correlation analysis between RDW and CRP, ESR, TNF-α, IL-6, and IL-10 in RA was conducted by Microsoft Excel. RDW level was significantly increased in RA patients compared to osteoarthritis (OA) patients (P < 0.001) and healthy donors (HDs) (P < 0.001), and RDW was positively associated with inflammatory markers, such as CRP and ESR. In ROC curve analysis, the area under the curve (AUC) of RDW for the identification of RA was 0.881, with a 95% confidence interval (CI) from 0.864 to 0.898. Moreover, correlation analysis showed that RDW level was positively associated with TNF-α and IL-6, however negatively associated with IL-10. RDW was increased in patients with RA which was associated with inflammation in RA, suggesting that RDW may be a potential auxiliary marker for indicating inflammation process in RA conveniently.

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To suppress sensor noise with unknown statistical properties, a novel self-adaptive direct laser absorption spectroscopy (SA-DLAS) technique was proposed by incorporating a recursive, least square (RLS) self-adaptive denoising (SAD) algorithm and a 3291 nm interband cascade laser (ICL) for methane (CH4) detection. Background noise was suppressed by introducing an electrical-domain noise-channel and an expectation-known-based RLS SAD algorithm. Numerical simulations and measurements were carried out to validate the function of the SA-DLAS technique by imposing low-frequency, high-frequency, White-Gaussian and hybrid noise on the ICL scan signal. Sensor calibration, stability test and dynamic response measurement were performed for the SA-DLAS sensor using standard or diluted CH4 samples. With the intrinsic sensor noise considered only, an Allan deviation of ~43.9 ppbv with a ~6 s averaging time was obtained and it was further decreased to 6.3 ppbv with a ~240 s averaging time, through the use of self-adaptive filtering (SAF). The reported SA-DLAS technique shows enhanced sensitivity compared to a DLAS sensor using a traditional sensing architecture and filtering method. Indoor and outdoor atmospheric CH4 measurements were conducted to validate the normal operation of the reported SA-DLAS technique.

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A Pound-Drever-Hall (PDH)-based mode-locked cavity-enhanced sensor system was developed using a distributed feedback diode laser centered at 1.53 µm as the laser source. Laser temperature scanning, bias control of the piezoelectric ceramic transducer (PZT) and proportional-integral-derivative (PID) feedback control of diode laser current were used to repetitively lock the laser modes to the cavity modes. A gas absorption spectrum was obtained by using a series of absorption data from the discrete mode-locked points. The 15 cm-long Fabry-Perot cavity was sealed using an enclosure with an inlet and outlet for gas pumping and a PZT for cavity length tuning. The performance of the sensor system was evaluated by conducting water vapor measurements. A linear relationship was observed between the measured absorption signal amplitude and the H2O concentration. A minimum detectable absorption coefficient of 1.5 × 10-8 cm-1 was achieved with an averaging time of 700 s. This technique can also be used for the detection of other trace gas species by targeting the corresponding gas absorption line.