Study on monitoring broken rails of heavy haul railway based on ultrasonic guided wave.

Real-time monitoring of broken rails in heavy haul railways is crucial for ensuring the safe operation of railway lines. U78CrV steel is a common material used for heavy haul line rails in China. In this study, the semi-analytical finite element (SAFE) method is employed to calculate the dispersion curves and modal shapes of ultrasonic guided waves in U78CrV heavy steel rails. Guided wave modes that are suitable for detecting rail cracks across the entire cross-section are selected based on the total energy of each mode and the vibration energy in the rail head, web, and foot. The excitation method for the chosen mode is determined by analyzing the energy distribution of the mode shape on the rail surface. The ultrasonic guided wave (UGW) signal in the rail is analyzed using ANSYS three-dimensional finite element simulation. The group velocity of the primary mode in the guided wave signal is obtained through continuous wavelet transform to confirm the existence of the selected mode. It is validated that the selected mode can be excited by examining the similarity between the vibration shapes of a specific rail section and all modal vibration shapes obtained through SAFE. Through simulation and field verification, the guided wave mode selected and excited in this study demonstrates good sensitivity to cracks at the rail head, web, and foot, and it can propagate over distances exceeding 1 km in the rail. By detecting the reflected signal of the selected mode or the degree of attenuation of the transmitted wave, long-distance monitoring of broken rails in heavy-haul railway tracks can be achieved.

G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.

Ultra-compact, low-loss,TE0- and TE1-compatible mode waveguide bends.

Waveguide bends have become an interesting research direction because they allow highly curved light transmission in a limited space. Here, we propose waveguide bends supporting two TE modes by etching slots and adding germanium arcs in the inner side of a waveguide bend. Simulations show that the bending radius of our proposed base-mode T E 0 waveguide bend drops to 500 nm and its insertion loss (IL) is reduced to 0.13 dB with footprints as small as 0.75µm×0.75µm. For the higher-order T E 1 mode waveguide bend, we adjust the introduced structure in combination with the light field distribution. The IL of the waveguide bend is also reduced to 0.18 dB with footprints as small as 1.85µm×1.85µm. T E 0 mode has 410 nm bandwidth in the optical communication band while T E 1 mode has 330 nm bandwidth by keeping I L<0.5d B. Through the analysis of these structural characteristics, we believe that this method still has great potential in higher-order mode transmission.

Compact mode converter on SOI based on a polygonal subwavelength grating structure.

In this Letter, we design and experimentally demonstrate compact mode converters with a lightning-like and arrow-like polygonal subwavelength grating (SWG) structure on a silicon-on-insulator (SOI) platform, which can convert the TE0 mode to the TE1 and TE2 modes, respectively. The footprints of the proposed TE0-1 and TE0-2 mode converters are only 4.44 × 1.3 and 5.89 × 1.8 µm2, respectively. The experimental results show the mode converters have a low insertion loss (<1 dB) and a broad bandwidth (>50 nm). The measured cross talks of the TE0-1 and TE0-2 mode converters are -7.2 dB and -10.3 dB, respectively. In addition, the proposed mode converters with the SWG structure have the advantage in fabrication, since only a one-step full-etching process is required.

A novel method for evaluating load restraint assemblies to ensure the safety of railway freight transportation.

The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

Molecular determinants within the C-termini of L-HDAg that regulate hepatitis D virus replication and assembly.

Background & Aims: Hepatitis D virus (HDV) is the causative agent of chronic hepatitis delta, the most severe form of viral hepatitis. HDV encodes one protein, hepatitis delta antigen (HDAg), in two isoforms: S- and L-HDAg. They are identical in sequence except that L-HDAg contains an additional 19-20 amino acids at its C-terminus, which confer regulatory roles that are distinct from those of S-HDAg. Notably, these residues are divergent between different genotypes. We aimed to elucidate the molecular determinants within the C-termini that are essential for the regulatory role of L-HDAg in HDV replication and assembly. Methods: Northern blot, reverse-transcription quantitative PCR, and a newly established HDV trans-complementary system were used in this study. Results: C-termini of L-HDAg, albeit with high sequence variation among different genotypes, are interchangeable with respect to the trans-inhibitory function of L-HDAg and HDV assembly. The C-terminus of L-HDAg features a conserved prenylation CXXQ motif and is enriched with proline and hydrophobic residues. Abolishment of the CXXQ motif attenuated the inhibitory effect of L-HDAg on HDV replication. In contrast, the enrichment of proline and hydrophobic residues per se does not modify the trans-inhibitory function of L-HDAg. Nevertheless, these residues are essential for HDV assembly. Mechanistically, prolines and hydrophobic residues contribute to HDV assembly via a mode of action independent of the prenylated CXXQ motif. Conclusions: Within the C-terminus of L-HDAg, the CXXQ motif and the enrichment of proline and hydrophobic residues are all essential determinants of L-HDAg's regulatory roles in HDV replication and assembly. This intrinsic viral regulatory mechanism we elucidated deepens our understanding of the unique life cycle of HDV. Impact and implications: Hepatitis D virus (HDV) encodes one protein, hepatitis delta antigen (HDAg), in two isoforms: S- and L-HDAg. They are identical in sequence except that L-HDAg contains an additional 19-20 amino acids at its C-terminus. This C-terminal extension in L-HDAg confers regulatory roles in the HDV life cycle that are distinct from those of S-HDAg. Herein, we found that C-termini of L-HDAg, although with high sequence variation, are interchangeable among different HDV genotypes. Within the C-terminus of L-HDAg, the prenylation motif, and the enrichment of proline and hydrophobic residues are all essential determinants of L-HDAg's regulatory roles in HDV replication and assembly.

Low loss and ultra-broadband design of an integrated 3 dB power splitter centered at 2 µm.

Because chemical gas is sensitive to absorption in the 2 µm band, and 2 µm matches the absorption band of the remote sensing material, many remote sensors and optical sensors are designed to operate in the 2 µm wavelength region. In this paper, we designed an integrated 3 dB power splitter centered at 2 µm. The study of this device is built on a silicon-on-insulator (SOI) platform. We introduced a subwavelength grating (SWG) to improve the performance of the device. We used the three-dimensional finite-difference time-domain (3D FDTD) method to analyze the effect of the structure on the power splitter. The insertion loss (IL) of the fundamental TE mode is only 0.04 dB at 2 µm and its bandwidth of IL <0.45d B is 940 nm (1570-2510 nm). It is suitable for multidomain and all-band photonic integrated circuits at 2 µm.

On-chip multifunctional polarizer based on phase change material.

Polarizers are used to eliminate the undesired polarization state and maintain the other one. The phase change material Ge2Sb2Se4Te1 (GSST) has been widely studied for providing reconfigurable function in optical systems. In this paper, based on a silicon waveguide embedded with a GSST, which is able to absorb light by taking advantage of the relatively large imaginary part of its refractive index in the crystalline state, a multifunctional polarizer with transverse electric (TE) and transverse magnetic (TM) passages has been designed. The interconversion between the two types of polarizers relies only on the state switching of GSST. The size of the device is 7.5µm∗4.3µm, and the simulation results showed that the extinction ratio of the TE-pass polarizer is 45.37 dB and the insertion loss is 1.10 dB at the wavelength of 1550 nm, while the extinction ratio (ER) of the TM-pass polarizer is 20.09 dB and the insertion loss (IL) is 1.35 dB. For the TE-pass polarizer, a bandwidth broader than 200 nm is achieved with ER>20dB and IL<2.0dB over the wavelength region from 1450 to 1650 nm  and for the TM-pass polarizer, ER>15dB and IL<1.5dB in the wavelength region from 1525 to 1600 nm, with a bandwidth of approximately 75 nm.

Hepatitis D infection induces IFN-ß-mediated NK cell activation and TRAIL-dependent cytotoxicity.

Background and aims: The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes. Methods: We established in vitro co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients. Results: Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-ß released by HDV-infected cells as an important enhancer of NK cell activity. In line with our in vitro data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients. Conclusion: Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.

Construction and functional verification of size-reduced plasmids based on TMP resistance gene dfrB10.

IMPORTANCE: Plasmid size is one of the factors affecting transfection efficacy in most of the molecular genetic research studies. One effective approach for reducing plasmid size is to replace relatively large, conventional antibiotic resistance genes with the short-size dfrB10 gene. The successful construct of a series of dfrB10-based tool plasmids and their functional validation, via comparison with original plasmids, suggest that dfrB10 is a potent drug resistance selection marker. The antibiotic trimethoprim offers convenient usage comparable to that of ampicillin or kanamycin. Additionally, fluorescence analysis has demonstrated the compatibility of TMP with protein expression in various host cells. Based on these findings, TMP-dfrB10 could be an alternative choice for future use in molecular genetic research studies that require miniature plasmids to achieve optimal results.

Examining the impact of perceived stress, anxiety, and resilience on depression among medical staff after COVID-19 quarantine: a chain mediation analysis.

Introduction: The COVID-19 pandemic and subsequent quarantine measures have led to a significant impact on mental health worldwide. Medical staff, in particular, have been exposed to high levels of stress due to their frontline work during the crisis. However, there is still limited research on the psychological mechanism among medical staff after quarantine. Methods: In this cross-sectional observational study, 150 medical staff from Shanghai YangZhi Rehabilitation Hospital, Shanghai, China, were enrolled in October 2022. SPSS 26.0 and PROCESS 4.0 model 6 were used to analyze the chain mediating effect of perceived stress, anxiety, resilience and depression among medical staff after quarantine. Anxiety and depression were compared during and after the quarantine. All scales have high validity and reliability in a Chinese population. Results: Our findings revealed a positive correlation between perceived stress and anxiety (r = 0.60, p < 0.001) and depression (r = 0.60, p < 0.001) levels among medical staff. Conversely, resilience was found to have a negative correlation with perceived stress (r = -0.67, p < 0.001), anxiety (r = -0.57, p < 0.001) and depression (r = -0.61, p < 0.001). The score of depression during the quarantine was higher than the score after the quarantine, but the p-value is only marginally significant (p = 0.067). The score of anxiety during the quarantine was significantly higher than the score after the quarantine (p < 0.05). Moreover, the chain mediation model suggested that anxiety and resilience could mediate the association between perceived stress and depression among medical staff following quarantine. Specifically, perceived stress had no direct effect on depression (ß = 0.025, t = 0.548, p = 0.59) but positively predicted anxiety (ß = 0.381, t = 8.817, p < 0.001) and resilience (ß = -1.302, t = -6.781, p < 0.001), which influenced depression levels indirectly through multiple pathways. The three indirect paths: the mediating role of anxiety, the mediating role of resilience, and the chain mediating role of both anxiety and resilience. Discussion: This study emphasizes the importance of psychological interventions aimed at protecting medical staff's psychological resilience and promoting coping mechanisms to manage stress during and after crises such as the COVID-19 pandemic. Additionally, our findings suggest that both anxiety and resilience play critical roles in mitigating the detrimental effects of perceived stress on mental health and further highlight the need for continued research to better understand the complex interplay of these factors.

Identification of Potential Protein Targets in Extracellular Vesicles Isolated from Chemotherapy-Treated Ovarian Cancer Cells.

Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.

Reconfigurable TE-pass polarizer based on lithium niobate waveguide assisted by Ge2Sb2Te5 and silicon nitride.

On-chip polarization management components play a critical role in tackling polarization dependence in the lithium-niobate-on-insulator (LNOI) platform. In this work, we proposed a reconfigurable TE-pass polarizer based on optical phase change material (GST) and the LNOI wafer. The key region is formed by a hybrid GST-S i 3 N 4 layer symmetrically deposited atop the centerline of the LNOI waveguide along the propagation direction where the GST is sandwiched in the middle of the S i 3 N 4 layer. Whether the polarizer will take effect depends on the phase states of the GST layer and the graphene and aluminum oxide layers are coated atop the G S T-S i 3 N 4 layer as the microheater to control the conversion of phase states. The proposed device length is 7.5 µm with an insertion loss (IL)=0.22 dB and extinction ratio (ER)=32.8 dB at the wavelength of 1550 nm. Moreover, it also has a high ER (>25d B) and a low IL (<0.5d B) in the operating bandwidth of 200 nm. Such a high-performance TE-pass polarizer paves a new way for applications of photonics integrated circuits.

Experiences of decisional conflict related to epidural labour analgesia among women during late pregnancy in a tertiary hospital in China: a mixed methods study.

BACKGROUND: Research has indicated some women were in a state of uncertainty about pharmacological pain management decisions, which may lead to maternal anxiety and decisional regret. However, little is known about decisional conflict in the choice of epidural labour analgesia amongst Chinese women. AIM: This study aimed to investigate the level of and reasons underlying decisional conflict in Chinese women during their late pregnancy when making a decision on the use of epidural analgesia in labour. METHODS: A convergent parallel mixed methods study was undertaken, that included a quantitative survey (n = 323) and qualitative interviews (n = 17) with women recruited from a tertiary general hospital in Hangzhou, China. The quantitative survey assessed the level of and its influencing factors of women's decisional conflict, while the qualitative interview further explored experiences of and reasons underlying the conflict. FINDINGS: Participants reported a high level of decisional conflict (mean±SD, 39.59±15.92), which related to decision delay and/or negative perceptions about the decision. Multiple stepwise linear regression analysis identified that highest level of education and knowledge of epidural were negatively associated with decisional conflict (p<0.05). Four decision-making styles (rational, dependant, intuitive and avoidant decision-making) associated with different levels of decisional conflict, and four underlying reasons (personal characteristics, informational provision, emotional support and participation in decision-making) of the conflict were thematized. CONCLUSION: Decisional conflict related to epidural labour analgesia is a noteworthy issue amongst women during their late pregnancy. This study suggests a need for provision of family-centred shared decision-making practice about the use of epidural analgesia in labour.

PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3.

Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases. Results: The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3. Conclusions: Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.

Association of diabetes mellitus with early-onset colorectal cancer: A systematic review and meta-analysis of 19 studies including 10 million individuals and 30,000 events.

BACKGROUND AND AIMS: Early-onset colorectal cancer (EoCRC) constitutes 2%-10% of all colorectal cancers and is becoming more common globally. Diabetes mellitus (DM) has increased substantially in younger adults; however, its involvement in EoCRC remains unclear. We conducted a systematic review and meta-analysis of observational studies to (1) explore the prevalence of DM in individuals with EoCRC and (2) investigate the association between DM and EoCRC. METHODS: A systematic literature search was conducted to identify studies published before May 2022 that evaluated the association between DM and EoCRC risk in four databases, including Medline (PubMed), Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. Results from the studies were summarized in meta-analyses using random effects models. RESULTS: Nineteen eligible studies were included. A total of 33,359 EoCRC cases and 14,259,289 controls in 12 studies were included in the meta-analysis. The pooled odds ratio [OR] of 1.43 (95% confidence interval [CI]: 1.08-1.8) indicated significant positive association between DM and increased risk of EoCRC. Subgroup analysis demonstrated that diabetes severity was significantly associated with unmanaged DM (OR = 1.28, 95% CI: 1.02-1.6), but not with managed DM (OR = 1.04, 95% CI: 0.84-1.28). CONCLUSION: Our results suggest that DM is a risk factor for EoCRC, and the higher prevalence of DM among younger adults may contribute to the increasing incidence of EoCRC. Interventions to reduce this bidirectional risk should be further investigated for the development of effective prevention and treatment strategies. PROSPERO registration: CRD42022306347.

Case report: Hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma: a rare case and review of the literature.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.

CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small group of genes, most of which were inducible by serum or PKC stimulation. Prolonged CDK8/19 inhibition or mutagenesis upregulated a larger gene set, along with a post-transcriptional increase in the proteins comprising the core Mediator complex and its kinase module. Regulation of both RNA and protein expression required CDK8/19 kinase activities but both enzymes protected their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Analysis of isogenic cell populations expressing CDK8, CDK19 or their kinase-inactive mutants revealed that CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression at the RNA and protein levels, whereas differential effects of CDK8 versus CDK19 knockouts were attributable to quantitative differences in their expression and activity rather than different functions.

Highly efficient and tunable polarization rotator based on lithium niobate on an insulator.

The lithium niobate on an insulator (LNOI) platform has greatly advanced the development of integrated photonics recently, where efficient polarization management components are indispensable. In this work, we propose a highly efficient and tunable polarization rotator based on the LNOI platform and the low-loss optical phase change material antimony triselenide (S b 2 S e 3). The key polarization rotation region is formed by a LNOI waveguide with a cross section of the double trapezoidal shape and a S b 2 S e 3 layer deposited atop the LNOI waveguide in an asymmetrical way, where an isolating layer of silicon dioxide is sandwiched between them to reduce the material absorption loss. Based on such a structure, we have achieved the efficient polarization rotation in a length of only 17.7 µm, where the polarization conversion efficiency and insertion loss are 99.6% (99.2%) and 0.38 dB (0.4 dB) for the trans-electric (TE)-to-trans-magnetic (TM) rotation. If we further change the phase state of the S b 2 S e 3 layer, other polarization rotation angles besides 90° can also be obtained for the same device, revealing a tunable function. We believe that the proposed device and design scheme could offer an efficient method for realizing the polarization management on the LNOI platform.

High-performance thin-film lithium niobate electro-optic modulator based on etching slot and ultrathin silicon film.

An electro-optic modulator (EOM) is an indispensable component to connect the electric and optical fields. Here, we propose a high-performance, thin-film lithium niobate-based EOM, where the modulation waveguide is formed by an etching slot on the lithium niobate film and the deposit of an ultrathin silicon film in the slot region. Therefore, a small mode size and high mode energy can be simultaneously achieved in the LN region with a high EO coefficient, which will be beneficial to increase the EO overlap and gradually decrease in the mode size. Further, we employed a waveguide structure to construct a typical Mach-Zehnder interference-type EOM. According to the requirements of high-speed traveling wave modulation, we conduct the index matching, impedance matching, and low-loss operation. From the results, the key half-wave voltage length product and 3 dB modulation bandwidth are, respectively, 1.45 V cm and 119 GHz in a modulation length of 4 mm. Moreover, a larger 3 dB bandwidth also can be achieved by shortening the modulation length. Therefore, we believe the proposed waveguide structure and EOM will provide new ways to enhance the performance of LNOI-based EOMs.