Genome-wide identification, molecular evolution and gene expression of P450 gene family in Cyrtotrachelus buqueti.

BACKGROUND: Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking. RESULTS: In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds. CONCLUSIONS: We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.

Internal standard optimization advances sensitivity and robustness of ratiometric detection method.

We design a p-aminothiophenol (pATP) modified Au/ITO chip to determine nitrite ions in lake water by a ratiometric surface-enhanced Raman scattering (SERS) method based on nitrite ions triggering the transformation of pATP to p,p'-dimercaptoazobenzene (DMAB). Intriguingly, by using the SERS peak (at 1008 cm-1) from benzoic ring deforming as an internal standard instead of the traditional peak at 1080 cm-1, the detection sensitivity of the method was improved 10 times.

Studying Transient Phenomena in Thin Films with Reinforcement Learning.

Neutron reflectometry has long been a powerful tool to study the interfacial properties of energy materials. Recently, time-resolved neutron reflectometry has been used to better understand transient phenomena in electrochemical systems. Those measurements often comprise a large number of reflectivity curves acquired over a narrow q range, with each individual curve having lower information content compared to a typical steady-state measurement. In this work, we present an approach that leverages existing reinforcement learning tools to model time-resolved data to extract the time evolution of structure parameters. By mapping the reflectivity curves taken at different times as individual states, we use the Soft Actor-Critic algorithm to optimize the time series of structure parameters that best represent the evolution of an electrochemical system. We show that this approach constitutes an elegant solution to the modeling of time-resolved neutron reflectometry data.

Correlation of serum anti-Mullerian hormone and Inhibin-B levels with osteoporosis of menopausal woman in Chinese Daur ethnic group.

PURPOSE: To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group. METHODS: A total of 175 menopausal women were selected and divided into the osteoporosis group (N = 90) and the control group (N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), ß-collagen special sequence (ß-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression. RESULTS: The level of BMD was decreased and the levels of OC, ß-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value. CONCLUSION: AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, ß-CTX, BALP, AMH, and InhB.

Unraveling the Role of Solvation and Ion Valency on Redox-Mediated Electrosorption through In Situ Neutron Reflectometry and Ab Initio Molecular Dynamics.

Solvation and ion valency effects on selectivity of metal oxyanions at redox-polymer interfaces are explored through in situ spatial-temporally resolved neutron reflectometry combined with large scale ab initio molecular dynamics. The selectivity of ReO4- vs MoO42- for two redox-metallopolymers, poly(vinyl ferrocene) (PVFc) and poly(3-ferrocenylpropyl methacrylamide) (PFPMAm) is evaluated. PVFc has a higher Re/Mo separation factor compared to PFPMAm at 0.6 V vs Ag/AgCl. In situ techniques show that both PVFc and PFPMAm swell in the presence of ReO4- (having higher solvation with PFPMAm), but do not swell in contact with MoO42-. Ab initio molecular simulations suggest that MoO42- maintains a well-defined double solvation shell compared to ReO4-. The more loosely solvated anion (ReO4-) is preferably adsorbed by the more hydrophobic redox polymer (PVFc), and electrostatic cross-linking driven by divalent anionic interactions could impair film swelling. Thus, the in-depth understanding of selectivity mechanisms can accelerate the design of ion-selective redox-mediated separation systems for transition metal recovery and recycling.

Research on ultrawideband photodetector module based on parasitic parameter regulation.

A four-channel ultrawideband photodetector (PD) module with a size of 26.1 mm ×33.2 mm × 8.5 mm has been demonstrated in our laboratory. We propose a method to improve the bandwidth of the PD module based on compensating parasitic parameters by dual resistance regulation on the P and N terminals of the PD chip. A small signal equivalent circuit model with package matching network is established for the PD module, and the effectiveness of the proposed method and the accuracy of the model are verified by experiments. A four-channel photodetector module with a -3 dB bandwidth of up to 67 GHz is fabricated by using photodetector chips with -3 dB bandwidths of 46 GHz, and the responsivity is up to 0.50A/W.

Photonic Weyl Waveguide and Saddle-Chips-like Modes.

Topological Weyl semimetals are characterized by open Fermi arcs on their terminal surfaces, these materials not only changed accepted concepts of the Fermi loop but also enabled many exotic phenomena, such as one-way propagation. The key prerequisite is that the two terminal surfaces have to be well separated, i.e., the Fermi arcs are not allowed to couple with each other. Thus, their interaction was overlooked before. Here, we consider coupled Fermi arcs and propose a Weyl planar waveguide, wherein we found a saddle-chips-like hybridized guiding mode. The hybridized modes consist of three components: surface waves from the top and bottom surfaces and bulk modes inside the Weyl semimetal. The contribution of these three components to the hybridized mode appears to be z-position-dependent rather than uniform. Beyond the conventional waveguide framework, those non-trivial surface states, with their arc-type band structures, exhibit strong selectivity in propagation direction, providing an excellent platform for waveguides. Compared with the conventional waveguide, the propagation direction of hybridized modes exhibits high z-position-dependency. For example, when the probe plane shifts from the top interface to the bottom interface, the component propagating horizontally becomes dimmer, while the component propagating vertically becomes brighter. Experimentally, we drilled periodic holes in metal plates to sandwich an ideal Weyl meta-crystal and characterize the topological guiding mode. Our study shows the intriguing behaviors of topological photonic waveguides, which could lead to beam manipulation, position sensing, and even 3D information processing on photonic chip. The Weyl waveguide also provides a platform for studying the coupling and the interaction between surface and bulk states.

The Construction of a Lattice Image and Dislocation Analysis in High-Resolution Characterizations Based on Diffraction Extinctions.

This paper introduces a method for high-resolution lattice image reconstruction and dislocation analysis based on diffraction extinction. The approach primarily involves locating extinction spots in the Fourier transform spectrum (reciprocal space) and constructing corresponding diffraction wave functions. By the coherent combination of diffraction and transmission waves, the lattice image of the extinction planes is reconstructed. This lattice image is then used for dislocation localization, enabling the observation and analysis of crystal planes that exhibit electron diffraction extinction effects and atomic jump arrangements during high-resolution transmission electron microscopy (HRTEM) characterization. Furthermore, due to the method's effectiveness in localizing dislocations, it offers a unique advantage when analyzing high-resolution images with relatively poor quality. The feasibility of this method is theoretically demonstrated in this paper. Additionally, the method was successfully applied to observed edge dislocations, such as 1/6[211-], 1/6[2-11-], and 1/2[01-1], which are not easily observable in conventional HRTEM characterization processes, in electro-deposited Cu thin films. The Burgers vectors were determined. Moreover, this paper also attempted to observe screw dislocations that are challenging to observe in high-resolution transmission electron microscopy. By shifting a pair of diffraction extinction spots and superimposing the reconstructed images before and after the shift, screw dislocations with a Burgers vector of 1/2[011-] were successfully observed in electro-deposited Cu thin films.

Prognostic implications of combining EGFR-TKIs and radiotherapy in Stage IV lung adenocarcinoma with 19-Del or 21-L858R mutations: A real-world study.

OBJECTIVE: To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19-Del) or exon 21 L858R mutation (21-L858R). METHODS: In this real-world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR-TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real-world study was overall survival (OS). RESULTS: The clinical characteristics of patients with Stage IV LUAD harboring 19-Del were similar to those harboring 21-L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6-35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19-Del group compared to the 21-L858R group, especially when EGFR-TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). CONCLUSIONS: Patients with Stage IV LUAD harboring 19-Del experience a notably prolonged OS following combined therapy with EGFR-TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19-Del and 21-L858R groups.

Primary cilia restrict autoinflammation by mediating PD-L1 expression.

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Ciprofol alleviates remifentanil-induced hyperalgesia by regulating α2GABAARs, NR2B, and P-CaMKIIα levels in the spinal cord and hippocampus.

OBJECTIVES: Several studies have shown that propofol administration during surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, a novel intravenous sedative agent analogous to propofol, has not yet been proven efficacious in alleviating RIH. The present study aimed to investigate the effect of ciprofol on RIH and the possible mechanisms involved. METHODS: The RIH model was established by an infusion of remifentanil (1 µg·kg-1·min-1) 60 min in rats with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg·kg-1·min-1) was simultaneously infused to evaluate its effect on RIH. The antinociception of ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). γ-aminobutyric acid type A receptor α2 subunit (α2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and phosphorylated CaMKIIα (P-CaMKIIα) in the spinal cord and hippocampus of rats were assessed by western blotting and immunohistochemistry. KEY FINDINGS: The results showed that ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, ciprofol upregulated α2GABAAR and downregulated NR2B and P-CaMKIIα in the rat spinal cord and hippocampus. CONCLUSIONS: Ciprofol alleviates RIH effectively, and the anti-hyperalgesic mechanisms may involve increasing α2GABAAR levels and decreasing NR2B and P-CaMKIIα levels in the spinal cord and hippocampus.

Twisted photonic Weyl meta-crystals and aperiodic Fermi arc scattering.

As a milestone in the exploration of topological physics, Fermi arcs bridging Weyl points have been extensively studied. Weyl points, as are Fermi arcs, are believed to be only stable when preserving translation symmetry. However, no experimental observation of aperiodic Fermi arcs has been reported so far. Here, we continuously twist a bi-block Weyl meta-crystal and experimentally observe the twisted Fermi arc reconstruction. Although both the Weyl meta-crystals individually preserve translational symmetry, continuous twisting operation leads to the aperiodic hybridization and scattering of Fermi arcs on the interface, which is found to be determined by the singular total reflection around Weyl points. Our work unveils the aperiodic scattering of Fermi arcs and opens the door to continuously manipulating Fermi arcs.

Optimal conditions for adenoviral transduction of immature dendritic cells without affecting the tolerogenic activity of DC-based immunotherapy.

Dendritic cells (DCs) play a pivotal role in maintaining immune tolerance. Using recombinant adenovirus (rAd) to deliver vectors to immature dendritic cells (imDCs) is an important method for studying the tolerogenic function of DCs. We found that using RPMI medium and a higher MOI during transduction increased the expression of CD80, CD86, and MHC-II on the surface of imDCs. Our data reveal a significant increase in the secretion of the pro-inflammatory cytokine IL-6 in the group showing the most pronounced phenotypic changes. In the mouse heart transplant model, imDCs with unstable phenotype and function due to adenoviral transduction resulted in an increased proportion of Th1 and Th17 cells in recipients. However, these effects can be managed, and our proposed optimized transduction strategy significantly minimizes these adverse effects. Our study holds significant implications for the development and optimization of immunotherapy utilizing tolerogenic dendritic cells.

Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae.

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health.

Boosting Electrocatalytic Ethylene Epoxidation by Single Atom Modulation.

The electrochemical synthesis of ethylene oxide (EO) using ethylene and water under ambient conditions presents a low-carbon alternative to existing industrial production process. Yet, the electrocatalytic ethylene epoxidation route is currently hindered by largely insufficient activity, EO selectivity, and long-term stability. Here we report a single atom Ru-doped hollandite structure KIr4O8 (KIrRuO) nanowire catalyst for efficient EO production via a chloride-mediated ethylene epoxidation process. The KIrRuO catalyst exhibits an EO partial current density up to 0.7 A cm-2 and an EO yield as high as 92.0 %. The impressive electrocatalytic performance towards ethylene epoxidation is ascribed to the modulation of electronic structures of adjacent Ir sites by single Ru atoms, which stabilizes the *CH2CH2OH intermediate and facilitates the formation of active Cl2 species during the generation of 2-chloroethanol, the precursor of EO. This work provides a single atom modulation strategy for improving the reactivity of adjacent metal sites in heterogeneous electrocatalysts.

The role of medical support workers during the COVID-19 pandemic in the NHS in the UK: A qualitative service evaluation at the Oxford University Hospitals NHS Foundation Trust.

We conducted a service evaluation of the medical support worker (MSW) role at Oxford University Hospitals NHS Foundation Trust following the Coronavirus 2019 (COVID-19) pandemic. The aim was to explore the roles of MSWs, their contributions to the NHS, factors influencing their career choices, and the goals of the MSW position, to inform quality improvement in relation to their integration into the Trust. The perspectives of MSWs, their supervisors and recruiters were analysed through nine semi-structured interviews and two focus group discussions involving 18 participants. Results were categorised into micro-, meso-, and macro-levels of the health system. At the micro-level, MSWs were recognised as a diverse group of highly qualified international medical graduates (IMGs) who had a crucial role during the pandemic. At the meso-level, participants emphasised the importance of a comprehensive induction by the hospital, to clarify responsibilities and familiarise MSWs with the health system. At the macro-level, the role facilitated MSW integration within the NHS, with the aim of practising as doctors. The importance of comprehensive hospital induction, with role clarity for both MSWs and their teams, supportive supervision and assistance with applying for registration with the General Medical Council, were highlighted as key quality improvement areas.

Schisandrin A alleviates renal fibrosis by inhibiting PKCß and oxidative stress.

BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.

Value of markers of systemic inflammation for the prediction of postoperative progression in patients with pancreatic neuroendocrine tumors.

Background: Non-invasive prognostic predictors for rare pancreatic neuroendocrine tumors (PNETs) are lacking. We aimed to approach the prognostic value of preoperative systemic inflammatory markers in patients with PNETs. Methods: The clinical data of 174 patients with PNETs undergoing surgical treatment were retrospectively analyzed to explore the correlation of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and platelet to white blood cell ratio (PWR) with clinicopathological parameters and the progression of tumor after the operation. The optimal cutoff values for predictors and the area under the curve (AUC) of the receiver operating characteristic (ROC) were estimated. Univariate and multivariate Cox proportional hazards models were used to assess the relation between NLR, LMR, PLR, and progression-free survival (PFS), examined by the Kaplan-Meier and log-rank tests. Results: The scores of the NLR (P = 0.039) and PLR (P = 0.011) in the progression group were significantly higher than those in the progression-free group, and the LMR was significantly lower than those in the progression-free group (P = 0.001). The best cutoff values of NLR, LMR, and PLR before operation were 2.28, 4.36, and 120.91. The proportions of tumor progression in the high NLR group (P = 0.007) and high PLR group (P = 0.013) obviously increased, and the proportion of tumor development in the low LMR group was higher than that in the high LMR group (P < 0.001). The K-M survival curve showed that the progression-free survival rate was lower in the high NLR group (P = 0.004), the low LMR group (P < 0.001), and the high PLR group (P = 0.018). The results of the multivariate Cox proportional hazards model suggested that preoperative LMR (HR = 3.128, 95% CI: 1.107~8.836, P = 0.031) was an independent predictor of PFS. Conclusion: The markers of systemic inflammation, especially LMR, can predict the postoperative progression of PNETs.

Charged Biological Membranes Repel Large Neutral Molecules by Surface Dielectrophoresis and Counterion Pressure.

Macromolecular crowding is the usual condition of cells. The implications of the crowded cellular environment for protein stability and folding, protein-protein interactions, and intracellular transport drive a growing interest in quantifying the effects of crowding. While the properties of crowded solutions have been extensively studied, less attention has been paid to the interaction of crowders with the cellular boundaries, i.e., membranes. However, membranes are key components of cells and most subcellular organelles, playing a central role in regulating protein channel and receptor functions by recruiting and binding charged and neutral solutes. While membrane interactions with charged solutes are dominated by electrostatic forces, here we show that significant charge-induced forces also exist between membranes and neutral solutes. Using neutron reflectometry measurements and molecular dynamics simulations of poly(ethylene glycol) (PEG) polymers of different molecular weights near charged and neutral membranes, we demonstrate the roles of surface dielectrophoresis and counterion pressure in repelling PEG from charged membrane surfaces. The resulting depletion zone is expected to have consequences for drug design and delivery, the activity of proteins near membrane surfaces, and the transport of small molecules along the membrane surface.