Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells Through Activating Ezrin.

Proteins containing a CAAX motif at the C-terminus undergo prenylation for localization and activity and include a series of key regulatory proteins, such as RAS superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal cancer are limited. Here, through research on large-scale proteomic data of esophageal cancer in our laboratory, we found that paralemmin-2 (PALM2), a potential prenylated protein, was upregulated and associated with poor prognosis in patients. Low-throughput verification showed that the expression of PALM2 in esophageal cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal cancer cells. PALM2 interacted with the two subunits of farnesyl transferase (FTase), FNTA and FNTB. Either the addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization and reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma cells, whereas PALM2C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of the ezrin/radixin/moesin (ERM) family. Mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin's FERM domain and C408 in PALM2's CAAX motif were important for PALM2/ezrin interaction and ezrin activation. Knockout of ezrin prevented enhanced cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, increased both ezrin membrane localization and phosphorylation of ezrin at Y146. In summary, prenylated PALM2 enhances the migration of cancer cells by activating ezrin.

Sulconazole Induces PANoptosis by Triggering Oxidative Stress and Inhibiting Glycolysis to Increase Radiosensitivity in Esophageal Cancer.

Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance remain problematic. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously showed that the Food and Drug Administration-approved drug sulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various types of programmed cell death and inhibit glycolysis and its related pathways. Experimentally, we found that sulconazole induced apoptosis, pyroptosis, necroptosis, and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress and inhibited glycolysis. Finally, we showed that low-dose sulconazole can increase radiosensitivity of esophageal cancer cells. Taken together, these new findings provide strong laboratory evidence for the clinical application of sulconazole in esophageal cancer.

Nitrogen-mediated volatilisation of defensive metabolites in tomato confers resistance to herbivores.

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.

Critical window for the association between early electronic screen exposure and hyperactive behaviors in preschool children.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA-MB-468 Cells by Altering Cell Energy Metabolism.

Triple-negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell-type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50 nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA-MB-468 cells. A short-term AA005 exposure markedly suppressed mitochondrial function in MDA-MB-468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K-AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy-producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the in vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.

Efficient mode exchanger-based silicon photonic switch enabled by inverse design.

A novel and energy efficient mode insensitive switch building block is proposed and experimentally demonstrated on a silicon-on-insulator platform. Based on a Mach-Zehnder interferometer, the switch uses a relatively compact mode insensitive phase shifter which includes a mode exchanger. The novel structure realizes the exact same phase shift for all modes by exchanging the modes midway within the phase shifter. The design approach leads to reduced power consumption otherwise not possible. Switching the first two quasi transverse electric (TE) modes simultaneously consumes 25.6 mW of power, an approximately 30% reduction from previous reported demonstrations. The measured insertion loss is 3.1 dB on average with a worst-case crosstalk of -14.9 dB over a 40 nm optical bandwidth from 1530 nm to 1570 nm. The design methodology enables scalability up to four optical modes.

Fabrication error tolerant broadband mode converters and their working principles.

Computational inverse design techniques have shown potential to become reliable means for designing compact nanophotonic devices without compromising the performance. Much effort has been made to reduce the computation cost involved in the optimization process and obtain final designs that are robust to fabrication imperfections. In this work, we experimentally demonstrate TE0-TE1 and TE1-TE3 mode converters (MCs) on the silicon-on-insulator platform designed using the computationally efficient shape optimization method. These MCs have mode conversion efficiencies above 95%, and the insertion loss ranges from 0.3 dB to 1 dB over a wavelength span of 80 nm ranging from 1.5 µm to 1.58 µm. Maximum modal crosstalk found experimentally in the C-band is -19 dB. The conversion efficiency drops at most by 2.2% at 1.55 µm for 10 nm over/under etch, implying good robustness to dimensional variations. We present the mode conversion mechanism of these MCs by studying the simulated electromagnetic field patterns and validate with supportive data. We also demonstrate their performance in the time domain with a 28 Gbps OOK and a 20 GBaud PAM-4 payload transmissions, which supports their utility for high throughput data communications. The open eye diagrams exhibit Q-factors of 8 dB.

Athermal echelle grating and tunable echelle grating demultiplexers using a Mach-Zehnder interferometer launch structure.

We present a comparative experimental study of three silicon photonic echelle grating demultiplexers that are integrated with a Mach-Zehnder interferometer (MZI) launch structure. By appropriate choice of the MZI configuration, the temperature induced shift of the demultiplexer channel wavelengths can be suppressed (athermal) or enhanced (super-thermal) or be controlled by an on-chip micro-heater. The latter two configurations allow the channel wavelengths to be actively tuned using lower power than possible by temperature tuning a conventional echelle demultiplexer. In the athermal configuration, the measured channel spectral shift is reduced to less than 10 pm/°C, compared to the 83 pm/°C shift for an unmodified echelle device. In super-thermal operation an enhanced channel temperature tuning rate of 170 pm/°C is achieved. Finally, by modulating the MZI phase with an on-chip heater, the demultiplexer channels can be actively tuned to correct for ambient temperature fluctuations up to 20 °C, using a drive current of less than 20 mA.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth.

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Association between prenatal exposure to indoor air pollution and autistic-like behaviors among preschool children.

Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.

Simultaneous subacute interstitial nephritis and anticoagulant-related nephropathy related to novel oral anticoagulants use.

Introduction: Interstitial nephritis related to novel oral anticoagulants was only reported in sporadic case reports and none was accompanied by anticoagulants related nephropathy (ARN).Case Report: We presented here a case of biopsy-proven subacute interstitial nephritis (SubAIN) accompanied by ARN after oral dabigatran to alarm clinicians. This case manifested with gross hematuria, acute kidney injury, slightly prolonged thrombin time, moderate anemia, moderate proteinuria, a large quantity of intratubular hemoglobin casts confirmed by hemoglobin antibody immunohistochemical staining which presumed to occur around 1 week after dabigatran and subacute interstitial nephritis accompanied by focal proliferative glomerulonephritis. Serum creatinine level did not continue to elevate after discontinuation of the oral anticoagulant. With the subsequent supportive therapy, it decreased to some extent then reduced to normal with the help of prednisone (half of the full dose).Conclusions: When we came across a patient who manifested as hematuria or acute kidney injury with a history of anticoagulants usage, we should think of ARN and pay more attention on history collection. Secondly, subacute interstitial nephritis may coexist with ARN. Thirdly, hemoglobin immunohistochemical staining may be helpful to make it clear whether the intra-tubular protein casts came from red blood cells. In addition, for those patients who may have decreased kidney function, anticoagulants dose should be reduced to prevent the occurrence of ARN.

Topological inverse design of nanophotonic devices with energy constraint.

In this paper, we introduce an energy constraint to improve topology-based inverse design. Current methods typically place the constraints solely on the device geometry and require many optimization iterations to converge to a manufacturable solution. In our approach the energy constraint directs the optimization process to solutions that best contain the optical field inside the waveguide core medium, leading to more robust designs with relatively larger minimum feature size. To validate our method, we optimize two components: a mode converter (MC) and a wavelength demultiplexer. In the MC, the energy constraint leads to nearly binarized structures without applying independent binarization stage. In the demultiplexer, it also reduces the appearance of small features. Furthermore, the proposed constraint improves the robustness to fabrication imperfections as shown in demultiplexer design. With energy constraint optimization, the corresponding spectrum shifts under ±10 nm dimensional variations are reduced by 17% to 30%. The proposed constraint is unique in simultaneously taking both geometry and electric field into account, opening the door to new ideas and insights to further improve the computationally intensive topology-based optimization process of nanophotonic devices.

Efficient Bloch mode calculation of periodic systems with arbitrary geometry and open boundary conditions in the complex wavevector domain.

We show how existing iterative methods can be used to efficiently and accurately calculate Bloch periodic solutions of Maxwell's equations in arbitrary geometries. This is carried out in the complex-wavevector domain using a commercial frequency-domain finite-element solver that is available to the general user. The method is capable of dealing with leaky Bloch mode solutions, and is extremely efficient even for 3D geometries with non-trivial material distributions. We perform independent finite-difference time-domain simulations of Maxwell's equations to confirm our results. This comparison demonstrates that the iterative mode finder is more accurate, since it provides the true solutions in the complex-wavevector domain and removes the need for additional signal processing and fitting. Due to its efficiency, generality and reliability, this technique is well suited for complex and novel design tasks in integrated photonics, and also for a wider range of photonics problems.

Compact and highly-efficient broadband surface grating antenna on a silicon platform.

We present a compact silicon-based surface grating antenna design with a high diffraction efficiency of 89% (-0.5 dB) and directionality of 0.94. The antenna is designed with subwavelength-based L-shaped radiating elements in a 300-nm silicon core, maintaining high efficiency with a compact footprint of 7.6 µm × 4.5 µm. The reflectivity remains below -10 dB over the S, C and L optical communication bands. A broad 1-dB bandwidth of 230 nm in diffraction efficiency is achieved with a central wavelength of 1550 nm.

Fiber Fabry-Perot astrophotonic correlation spectroscopy for remote gas identification and radial velocity measurements.

We present a novel, to the best of our knowledge, remote gas detection and identification technique based on correlation spectroscopy with a piezoelectric tunable fiber-optic Fabry-Perot filter. We show that the spectral correlation amplitude between the filter transmission window and gas absorption features is related to the gas absorption optical depth, and that different gases can be distinguished from one another using their correlation signal phase. Using a previously captured telluric-corrected high-resolution near-infrared spectrum of Venus, we show that the radial velocity of Venus can be extracted from the phase of higher order harmonic lock-in signals. This correlation spectroscopy technique has applications in the detection and radial velocity determination of weak spectral features in astronomy and remote sensing. We experimentally demonstrate a remote CO2 detection system using a lock-in amplifier, fiber-optic Fabry-Perot filter, and single channel avalanche photodiode.

High-throughput next-generation sequencing for identifying pathogens during early-stage post-lung transplantation.

BACKGROUND: High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. METHODS: In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. RESULTS: HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P < 0.001). For three LTx recipients, treatment regimens were adjusted according to the results of HT-NGS, leading to a complete recovery. CONCLUSION: HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.

Determination of Mineral Elements in Nanyang Mugwort (Artemisia argyi) Leaves Harvested from Different Crops by Inductively Coupled Plasma Mass Spectrometry and Inductively Coupled Plasma Atomic Emission Spectrometry.

Due to high need for medical purposes, multiple harvests of mugwort (Artemisia argyi) have been extensively applied in China for the increase of mugwort yield recently. However, the investigation on the mineral elements in different crops, which are significantly related to mugwort growth and the clinical efficacy of this medicinal herb, has not been conducted. This study provided an analytical method and quality evaluation for mineral elements in Nanyang mugwort leaves harvested from three different crops. The contents of 35 mineral elements were determined by inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). ANOVA, principal component analysis and factor analysis were applied to evaluate the results. Four principal components were identified and their comprehensive evaluation function was as follows: F = 0.7008Fl + 0.1236F2 + 0.0936F3 + 0.0321F4. The comprehensive scores of the mugwort leaves from different crops were ranked as follows: 3rd crop > 2nd crop ≈ 1st crop. These findings can provide a reference for the quality control and clinical use of mugwort leaves, and a guidance of differential nourishing strategies for different crops.

Screen time and autistic-like behaviors among preschool children in China.

Screen time is becoming increasingly common in daily life. Early and excessive screen use has raised growing concerns for children's neuropsychological development. The purpose of this study was to evaluate the association between exposure to screen time in early life and the presence of autistic-like behaviors among preschool children. 29,461 child-caregiver dyads at kindergartens in Longhua New District of Shenzhen, China, were enrolled in this cross-sectional study. Information concerning socio-demographic characteristics, frequency and duration of children's electronic screen exposure for each year since birth, and autistic-like behaviors (measured by the Autism Behavior Checklist) were collected using a self-administered structured questionnaire completed by the primary caregivers. A series of logistic regression models assessed the association between screen time and autistic-like behaviors. Results indicated that younger initial age, longer daily screen time and longer cumulative years of screen exposure since birth were associated with the presence of autistic-like behaviors at preschool age. The risk was enhanced with the increase of both daily screen time and cumulative years of screen exposure during preschool period. Moreover, the cross-over analysis indicated that the first three years following birth might be a sensitive period for children when screen exposure increases the risk of experiencing autistic-like behaviors. In conclusion, our study implied that screen exposure in early life might increase the occurrence of autistic-like behaviors among preschoolers. These findings support the need for early interventions into preschoolers' screen use, however longitudinal studies are necessary to further confirm the causal relationship between early screen time and the incidence of later autistic-like behaviors among preschool children.

Photonic temperature and wavelength metrology by spectral pattern recognition.

Spectral pattern recognition is used to measure temperature and generate calibrated wavelength/frequency combs using a single silicon waveguide ring resonator. The ring generates two incommensurate interleaving TE and TM spectral combs that shift independently with temperature to create a spectral pattern that is unique at every temperature. Following an initial calibration, the ring temperature can be determined by recognizing the spectral resonance pattern, and as a consequence, the wavelength of every resonance is also known. Two methods of pattern-based temperature retrieval are presented. In the first method, the ring is locked to a previously determined temperature set-point defined by the coincidence of only two specific TE and TM cavity modes. Based on a prior calibration at the set-point, the ring temperature and hence all resonance wavelengths are then known and the resulting comb can be used as a wavelength calibration reference. In this configuration, all reference comb wavelengths have been reproduced within a 5 pm accuracy across an 80 nm range by using an on-chip micro-heater to tune the ring. For more general photonic thermometry, a spectral correlation algorithm is developed to recognize a resonance pattern across a 30 nm wide spectral window and thereby determine ring temperature continuously to 50 mK accuracy. The correlation method is extended to simultaneously determine temperature and to identify and correct for wavelength calibration errors in the interrogating light source. The temperature and comb wavelength accuracy is limited primarily by the linewidth of the ring resonances, with accuracy and resolution scaling with the ring quality factor.