Real-time stealth optical transmission via fast laser frequency dithering.

We report a real-time 150 kbps stealth transmission within public optical communication of 10 Gbps dual polarization QPSK. The stealth data is modulated onto the frequency tuning signals of a fast-tuning laser source in the transmitter, which causes slight frequency dithering for the transmitted optical signal. In the receiver, the stealth receiver recovers the stealth data from the estimated frequency offset by the QPSK DSP algorithm. The experiments show the stealth transmission has few impacts on the public channel over a 300 km distance. The proposed method is fully compatible with existing optical transmission systems, and the only hardware change is to upgrade the transmitter laser to support frequency tuning through an external analog port for receiving stealth signal. The proposed stealth scheme can combine with cryptographic protocols to improve the integrated security of the system, and can be used as signaling transport for low level network control to reduce the communication overhead.

A histidine-rich fusion tag enables real-time monitoring of recombinant protein expression by Pauly reaction-based colorimetric assay.

Commercially available recombinant expression systems always use fusion tags to facilitate target protein purification and SDS-PAGE analysis followed by Coomassie Brilliant Blue (CBB) staining is the classical method to validate the expression level of target protein, which is time-consuming, although not very laborious. Previously, we found that a histidine-rich elastin-like polypeptide (HRELP) tag could make its fusion proteins being quickly and specifically stained with Pauly's reagent. In this study, we designed a Pauly reaction-based colorimetric assay to real-time monitoring of the expression level of recombinant protein tagged HRELP and found that the absorption value of post-induction E. coli cells stained with Pauly's reagent correlated well with both the band intensity of the target protein from Pauly's reagent-stained and CBB-stained gels. Moreover, we found the colorimetric assay could also be helpful to roughly estimate the expression efficiency by using a poly-histidine-tagged protein, which has only 1.17% histidine residue. In our opinion, Pauly reaction-based colorimetric assay could significantly shorten the time to validate the over-expression of recombinant protein tagged with either HRELP or poly-histidine. And HRELP seemed to be an ideal fusion tag for it can not only facilitate protein purification but also simplify protein detection.

Enhancement of the phase sensitivity with two-mode squeezed coherent state based on a Mach-Zehnder interferometer.

We theoretically study the phase estimation based on a Mach-Zehnder interferometer (MZI) with a two-mode squeezed coherent state. By maximizing the quantum Fisher information, we find that the quantum Cramér-Rao bounds (QCRB) can reach sub-Heisenberg limit under the phase-matched condition. The optimal phase sensitivity can reach the sub-shot noise limit (SNL) and approach the QCRB by employing the intensity difference detection. Meanwhile, compared with the MZI fed with a coherent plus a single-mode squeezed vacuum state, this scheme can have better performance by adjusting the squeezing parameter and the mean photon number. With the same parameter, our scheme shows more sensitive phase measurement than the SU(1,1) interferometer with a coherent plus a vacuum state. We also show that the phase sensitivity of our proposal can still reach the SNL when the loss of the photon is 36%. This scheme can provide potential applications in optical sensors.

Real-time stealth optical transmission via dither-remodulation in a bias controller of a Mach-Zehnder modulator.

The physical layer transmission security is a promising technology against security threats. As an effective supplement to the encryption strategy, steganography has received widespread attention. We report a real-time 2 kbps stealth transmission in the 10 Gbps dual polarization QPSK public optical communication. The stealth data is embedded in dither signals via precise and stable bias control technique for a Mach-Zehnder modulator. In the receiver, the stealth data can be recovered from the normal transmission signals by low SNR signal processing and digital down conversion. The stealth transmission has been verified to pose almost no impact on the public channel over a 117 km distance. The proposed scheme is compatible with existing optical transmission systems, so that no new hardware needs to be employed. It can be accomplished and is exceeded economically by adding simple algorithms, which utilizes only a small amount of FPGA resources. The proposed method can cooperate with encryption strategies or cryptographic protocols at different network layers to reduce the communication overhead and improve the overall security of the system.

A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Discovery of novel indazole derivatives as SOS1 agonists that activate KRAS signaling.

KRAS serves as a vital regulator for cellular signaling and drives tumor pathogenesis after mutation. Despite extensive research efforts spanning several decades, targeting KRAS is still challenging due to the multiple KRAS mutations and the emergence of drug resistance. Interfering the interactions between KRAS and SOS1 is one of the promising approaches for modulating KRAS functions. Herein, we discovered small-molecule SOS1 agonists with novel indazole scaffold. Through structure-based optimization, compound 11 was identified with high SOS1 activation potency (p-ERK EC50 = 1.53 µM). In HeLa cells, compound 11 enhances cellular RAS-GTP levels and exhibits biphasic modulation of ERK1/2 phosphorylation through an on-target mechanism and presents the therapeutic potential to modulate RAS signaling by activating SOS1.

Coagulation after paediatric miniaturised versus conventional cardiopulmonary bypass: Retrospective cohort study.

BACKGROUND: Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). METHODS: We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score-matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. RESULTS: A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. CONCLUSIONS: Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss.

The novel STAT3 inhibitor WZ-2-033 causes regression of human triple-negative breast cancer and gastric cancer xenografts.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Impact of miniaturized cardiopulmonary bypass circuits on ultrafiltration during congenital heart surgery.

OBJECTIVE: To investigate whether the miniaturized cardiopulmonary bypass (CPB) system decreased the usage of ultrafiltration (UF), and to explore whether the non-UF with miniaturized CPB strategy could get good clinical results during congenital heart surgery. METHODS: We performed a retrospective analysis of all patients undergoing congenital heart surgery with CPB at Shenzhen Children's Hospital from 1 May 2015 to 30 September 2019. We classified patients to UF with miniaturized CPB group, non-UF with miniaturized CPB group, UF with conventional CPB group and non-UF with conventional CPB group. RESULTS: Of the 2145 patients, 721 (33.6%) were in the conventional CPB group, and 1424 (66.4%) were in the miniaturized CPB group. The UF rate was significantly lower in the miniaturized CPB group compared with that in the conventional CPB group (12.5% vs. 76.8%, p < 0.001). Compared with patients in the other groups, patients in the non-UF with miniaturized CPB group had a shorter postoperative MV time (p < 0.05), and a shorter length of stay in the ICU (p < 0.001) and hospital (p < 0.001). The age of children in the UF with miniaturized CPB group was relatively younger (median: 1.5 months, IQR: 0.3-4.6 months), and the preoperative weight was relatively lower (median: 3.9 kg, IQR: 3.2-5.4 kg). Moreover, this group of children had a relatively longer postoperative MV time and length of stay in the ICU and hospital. CONCLUSION: The miniaturized CPB system could decrease the usage of UF. Good results were achieved in children who did not use UF based on the miniaturized CPB circuit system during congenital heart surgery.

Ultra-sensitive phase measurement based on an SU(1,1) interferometer employing external resources and substract intensity detection.

A new scheme has been proposed to realize the enhancement of phase sensitivity based on an SU(1,1) interferometer. Compared with the classical Mach-Zehnder interferometer, the SU(1,1) interferometer is splitted and recombined by an optical parametric amplifier and the phase sensitivity can beat shot noise limit by adjusting the parametric strength. In this model, the inputs of the SU(1,1) interferometer are bright entangled twin beams generated from four wave mixing and the detection method is substract intensity difference with one of the twin beams entering into the interferometer. The detection efficiency of the detector is taken into consideration. This scheme also proves that when one of the inputs of an SU(1,1) interferometer is an vacuum beam, the phase sensitivity can beat shot noise limit by employing substract intensity detection and external resources.

The Experience of Early Extubation After Paediatric Congenital Heart Surgery in a Chinese Hospital.

BACKGROUND: Early extubation has become widely adopted in cardiac surgery practices. This study aimed to present experience of early extubation after congenital heart surgery and to explore the factors that affect successful immediate postoperative extubation and early extubation. METHODS: A retrospective analysis was performed of all patients who underwent congenital heart surgery with cardiopulmonary bypass (CPB) at Shenzhen Children's Hospital between 01 May 2015 and 30 September 2019. The demographic and cardiac surgery information were derived from the medical records. Multivariable logistic regression models were used to explore the influence factors for successful immediate postoperative extubation and early extubation. RESULTS: This study consisted of 2,060 patients, 65.0% of whom were extubated in the operating room and 16.1% of whom were extubated early (within 6 hours) in the Intensive Care Unit. The overall rates of reintubation and nasal continuous positive airway pressure were 2.0% and 6.4%, respectively. Preoperative weight (OR, 1.24; 95% CI, 1.20-1.29), preoperative pneumonia (OR, 0.60; 95% CI, 0.44-0.80), CPB type (OR, 1.23; 95% CI, 1.06-1.43), CPB time (OR, 0.98; 95% CI, 0.98-0.99), deep hypothermic circulatory arrest (OR, 0.42; 95% CI, 0.25-0.70), and Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery (STAT) categories (OR, 0.54; 95% CI, 0.45-0.65) were included in the immediate postoperative extubation model. In addition to the above six variables, ultrafiltration (OR, 0.63; 95% CI, 0.44-0.89) was also included in the early extubation model. Similar results were found in the immediate postoperative extubation model for non-newborns. The influencing factors for early extubation in the non-newborn population included preoperative weight, preoperative pneumonia, ultrafiltration, CPB time, and STAT categories. CONCLUSIONS: Early extubation for children with congenital heart surgery was successful in this hospital. Patients with early extubation had a lower reintubation rate and nasal continuous positive airway pressure rate, and a shorter length of stay in the ICU and hospital. Early extubation was influenced by age, weight at surgery, preoperative pneumonia, CPB type, CPB time, deep hypothermic circulatory arrest, ultrafiltration, and STAT categories.

Control of laser light by a plasma immersed in a tunable strong magnetic field.

The interaction between laser light and an underdense plasma immersed in a spatio-temporally tunable magnetic field is studied analytically and numerically. The transversely nonuniform magnetic field can serve as a magnetic channel, which can act on laser propagation in a similar way to the density channel. The envelope equation for laser intensity evolution is derived, which contains the effects of magnetic channel and relativistic self-focusing. Due to the magnetic field applied, the critical laser power for relativistic self-focusing can be significantly reduced. Theory and particle-in-cell simulations show that a weakly relativistic laser pulse can propagate with a nearly constant peak intensity along the magnetic channel for a distance much longer than its Rayleigh length. By setting the magnetic field tunable in both space and time, the simulation further shows that the magnetized plasma can then act as a lens of varying focal length to control the movement of laser focal spot, decoupling the laser group velocity from the light speed c in vacuum.

Application of Thiol-yne/Thiol-ene Reactions for Peptide and Protein Macrocyclizations.

The application of thiol-yne/thiol-ene reactions to synthesize mono- and bicyclic-stapled peptides and proteins is reported. First, a thiol-ene-based peptide-stapling method in aqueous conditions was developed. This method enabled the efficient stapling of recombinantly expressed coil-coiled proteins. The resulting stapled protein demonstrated higher stability in its secondary structure than the unstapled version. Furthermore, a thiol-yne coupling was performed by using an α,ω-diyne to react with two cysteine residues to synthesize a stapled peptide with two vinyl sulfide groups. The stapled peptide could further react with another biscysteine peptide to yield a bicyclic stapled peptide with enhanced properties. For example, the cell permeability of a stapled peptide was further increased by appending an oligoarginine cell-penetrating peptide. The robustness and versatility of thiol-yne/thiol-ene reactions that can be applied to both synthetic and expressed peptides and proteins were demonstrated.

Real-time experimental demonstration of PS-QPSK transmission with manipulated rotating and novel correlated CMA.

In this paper, we propose a novel manipulated rotating polarization switched quadrature phase shift keying (MR-PS-QPSK) technique, and corresponding correlated constant modulus algorithm (CMA) for signal recovery. The latter utilizes the correlation between the PS-QPSK symbols in the two polarizations to lock the phase of output signals. Then the signals in the two polarizations are merged according to the recovered switching bit, which suppresses the noise and simplifies the subsequent process. A field programmable gate array (FPGA) based real-time platform is built for experimental demonstration. The experimental results show that the proposed MR-PS-QPSK modulation format with correlated CMA can provide 3.2 dB optical signal-to-noise ratio (OSNR) improvement over dual-polarization QPSK (DP-QPSK) at back-to-back case and 3.8 dB OSNR improvement after fiber transmission at the same symbol rate, which corresponds to be about 2 dB OSNR improvement at the same bit rate. The resource consumption analysis in FPGA digital signal processing blocks and logic utilizations shows that the MR-PS-QPSK with correlated CMA only requires a small additional computational effort.

[A preliminary investigation of relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease].

OBJECTIVE: To preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease. METHODS: One hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery. RESULTS: The non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05). CONCLUSIONS: The decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

Metal-free, efficient hydrazination of imidazo[1,2-a]pyridine with diethyl azodicarboxylate in neutral media.

The first example of metal-free regioselective hydrazination of imidazo[1,2-a]pyridine with diethyl azodicarboxylate is accomplished. This procedure is chemically appealing due to the high degree of functional group tolerance and efficiency in expanding the molecular diversity.

A Thiol-Ene Coupling Approach to Native Peptide Stapling and Macrocyclization.

We report the discovery of a peptide stapling and macrocyclization method using thiol-ene reactions between two cysteine residues and an α,ω-diene in high yields. This new approach enabled us to selectively modify cysteine residues in native, unprotected peptides with a variety of stapling modifications for helix stabilization or general macrocyclization. We synthesized stapled Axin mimetic analogues and demonstrated increased alpha helicity upon peptide stapling. We then synthesized stapled p53 mimetic analogues using pure hydrocarbon linkers and demonstrated their abilities to block the p53-MDM2 interaction and selectively kill p53 wild-type colorectal carcinoma HCT-116 cells but not p53 null cells. In summary, we demonstrated a robust and versatile peptide stapling method that could be potentially applied to both synthetic and expressed peptides.

Discovery of the First-in-Class RORγ Covalent Inhibitors for Treatment of Castration-Resistant Prostate Cancer.

Nuclear receptor receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor and has been established as a key player in castration-resistant prostate cancers (CRPC) by driving androgen receptor (AR) overexpression, representing a potential therapeutical target for advanced prostate cancers. Here, we report the identification of the first-in-class RORγ covalent inhibitor 29 via the structure-based drug design approach following structure-activity relationship (SAR) exploration. Mass spectrometry assay validated its covalent inhibition mechanism. Compound 29 significantly inhibited RORγ transcriptional activity and remarkably suppressed the expression levels of AR and AR-targeted genes. Compound 29 also exhibited much superior activity in inhibiting the proliferation and colony formation and inducing apoptosis of the CRPC cell lines relative to the positive control 2 and noncovalent control 33. Importantly, it markedly suppressed the tumor growth in a 22Rv1 mouse tumor xenograft model with good safety. These results clearly demonstrate that 29 is a highly potent and selective RORγ covalent inhibitor.

Discovery of a Highly Potent Lysine Methyltransferases G9a/NSD2 Dual Inhibitor to Treat Solid Tumors.

Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16 demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3 and NSD2 inhibitor 15. In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16 as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.

[Protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease].

OBJECTIVE: To study the protective effect of cold autologous blood cardioplegic solution on the heart of infants with cyanotic congenital heart disease (CCHD). METHODS: Ninety-six infants with CCHD who underwent cardiopulmonary bypass (CPB) were randomly and equally divided into three groups: histidine-tryptophan-ketoglutarate (HTK) solution, cold non-autologous blood cardioplegic solution, and cold autologous blood cardioplegic solution. The right auricular tissues were taken before aortic cross-clamping and at 30 minutes after aortic declamping, and ATP level and energy charge (EC) in the myocardium were measured. Venous blood was collected before and immediately after CPB, and the serum levels of creatine kinase (CK)-MB and cardiac troponin I (cTnI) were measured. The clinical parameters, such as the re-beat time and re-beat rate during CPB, cardiac index, dependence on positive inotropic agents, and left ventricular ejection fraction (LVEF) at 2 hours after CPB, the incidence rate of arrhythmia within 24 hours after CPB, and postoperative complications and mortality, were recorded. RESULTS: At 30 minutes after aortic declamping, the three groups showed significantly decreased ATP and EC levels (P<0.05), and the cold autologous blood group had significantly higher ATP and EC levels than the other two groups (P<0.05). Immediately after CPB, the three groups showed significantly increased serum levels of CK-MB and cTnI (P<0.05), and the cold autologous blood group had significantly lower serum levels of CK-MB and cTnI than the other two groups (P<0.05). The cold autologous blood group had significantly better outcomes than the other two groups in terms of the re-beat time during CPB and the dependence on positive inotropic agents and LVEF at 2 hours after CPB (P<0.05). CONCLUSIONS: Cold autologous blood cardioplegic solution is superior to HTK and cold non-autologous blood cardioplegic solutions in preserving myocardial energy and reducing myocardial injury in infants with CCHD who undergo CPB, thus providing a better protective effect on the heart.