Search

Breast cancer is one of the most prevalent malignancies, necessitating the exploration of more effective synergistic treatment strategies to overcome the limitations of conventional therapies. Chemodynamic therapy (CDT) is an innovative antitumor approach that can be combined with chemotherapy to achieve potent synergistic effects. Mesoporous silica nanomaterials (MSNs) are ideal drug delivery vehicles in cancer therapy due to their unique advantages. This study presents an effective and straightforward strategy to design an intelligent drug delivery system (DDS) activated by the tumor-specific weakly acidic microenvironment to achieve efficient cancer treatment. By incorporating the chemotherapeutic drug doxorubicin (DOX) and divalent iron (Fe2+) into the unique mesoporous channels of MSNs, we fabricated MSNs@Fe2+@DOX. Under weakly acidic pH conditions, the functional components Fe2+ and DOX of MSNs@Fe2+@DOX are gradually released at the tumor site. The released Fe2+ can then consume hydrogen peroxide (H2O2) in tumor cells, increasing the levels of reactive oxygen species (ROS) and lipid peroxides through the Fenton reaction, thereby inducing ferroptosis. The combination of DOX-induced apoptosis and ferroptosis results in further enhanced cancer treatment. In vitro and in vivo experiments demonstrated that MSNs@Fe2+@DOX had an excellent therapeutic effect on breast cancer cells and tumor-bearing nude mice. We anticipate that this study will provide a promising biotechnological platform for combined breast cancer treatment by inducing CDT and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The relationship between sedentary time, physical activity, and chronic back pain remains unclear. The study aims to investigate whether sedentary time and physical activity predict chronic back pain and morphological brain changes. Methods: This cohort study recruited adults aged 37–73 years enrolled between 2006 and 2010, with follow-up until 2014. The total cohort comprised 33,402 participants (mean age: 54.53). Data were collected on daily sedentary time, physical activity, lifestyle factors, and health outcomes. Results: After nearly 8-year follow-up, 3,006 individuals (9.00%) reported chronic back pain in total. Individuals with daily sedentary time exceeding 6 h had a 33% higher risk of chronic back pain compared to those with sedentary time of 2 h or less (RR, 1.33, 95%CI, 1.17–1.52). Sedentary time was also associated with decreased grey matter volume in several brain regions, including bilateral primary somatosensory cortex (S1), secondary somatosensory cortex, putamen, primary motor cortex (M1), insula, hippocampus, amygdala, as well as right supplementary motor area, left medial frontal cortex, and right anterior cingulate cortex (FDR-corrected p-value < 0.05). Compared to individuals who sat for more than 6 h with light physical activity, those engaging in moderate physical activity with sedentary time of 2 h or less (RR, 0.71, 95%CI, 0.52–0.99) exhibited a significant decrease in chronic back pain risk. In addition, replacing sedentary time with equivalent amount of physical activity also demonstrated a reduction in the risk of chronic back pain (RR, 0.87, 95%CI, 0.77–0.99) and increased the reginal grey matter volumes including the amygdala, insula, M1, putamen and S1. Conclusions: Prolonged sedentary time is associated with heightened risks of chronic back pain and deterioration in brain health. [ABSTRACT FROM AUTHOR]

Modern pharmacological studies have elucidated the presence of aconitine (AC) alkaloids, polysaccharides, and saponins as the primary bioactive constituents of Fuzi. Among these, benzoylaconine, a pivotal active compound, demonstrates notable pharmacological properties including antitumor, anti‐inflammatory, and cardiovascular protective effects. In recent years, benzoylaconine has garnered significant attention in basic research on heart diseases, emerging as a focal point of investigation. This paper presents a comprehensive review of the pharmacological effects of benzoylaconine, alongside an overview of advancements in metabolic characterization. The objective is to furnish valuable insights that can serve as a cornerstone for further exploration, utilization, and advancement of benzoylaconine in pharmacological research. [ABSTRACT FROM AUTHOR]

We propose a new approach capable of measuring local seismic anisotropy from 6C (three‐component translation and three‐component rotation) amplitude observations of ambient seismic noise data. Our recent theory demonstrates that the amplitude ratio of 6C cross‐correlation functions (CCFs) enables retrieving the local phase velocity. This differs from conventional velocity extraction methods based on the travel time. Its local sensitivity kernel beneath the 6C seismometer allows us to study anisotropy from azimuth‐dependent CCFs, avoiding path effects. Such point measurements have great potential in planetary exploration, ocean bottom observations, or volcanology. We apply this approach to a small seismic array at Pin˜ $\widetilde{n}$on Flat Observatory (PFO) in southern California, array‐deriving retrieves rotational ground motions from microseismic noise data. The stress‐induced anisotropy is well resolved and compatible with other tomography results, providing constraints on the origin of depth‐dependent seismic anisotropy. Plain Language Summary: In contrast to the well‐known translational displacement of seismic waves, rotation measures the angle of rotation of a point in a medium as it deforms. Traditionally, the travel time of cross‐correlation functions of translational displacement of ambient seismic noise and its corresponding propagation distance is used to calculate the velocity of the subsurface medium. However, our recent theory shows that the amplitude ratio of translational displacement and rotation allows us to reveal the local velocity of the medium beneath the receiver from ambient seismic noise data and to study anisotropy from earthquake events. This paper points out for the first time that the amplitude observations of 6C cross‐correlation functions of ambient seismic noise provide a new approach to measure the azimuth‐dependent velocity in anisotropic media. Key Points: We show a new approach enabling the extraction of local phase velocity from 6C cross‐correlation functions of ambient noise dataAzimuth‐dependent 6C cross‐correlation functions allow us to study local seismic anisotropy and its depth dependenceLocal anisotropy at Pin˜ $\widetilde{n}$on Flat Observatory is compatible with compression stress, providing constraints on stress‐induced anisotropy [ABSTRACT FROM AUTHOR]

Seismic anisotropy in the upper mantle reveals geodynamic processes and the tectonic evolution of the Earth. The two most powerful methods, surface wave tomography, and shear‐wave splitting observations, cannot investigate the deep local anisotropy with good vertical and lateral resolution, resulting in poor constraints on plate deformation processes of the complex plate boundary beneath the Southern California region. Here, we show that the amplitude ratio of translational displacement and rotation makes it possible to retrieve the local anisotropy in the upper mantle. Azimuthal anisotropy in the asthenosphere is well determined and resolved in lateral and vertical directions. The fast axis retrieved from amplitude observations indicates the local rapid changes in plate deformation and complex pattern of mantle flow, which is compatible with the distributions of horizontal mantle flow illuminated by geodetic measurements, providing new insights on geodynamic processes of the Southern California region. Plain Language Summary: Rotational motion is the angle of ground rotation observed during Earth's deformation, and the ratio of amplitude to translational motion is sensitive to local structure. In the past few decades, study on the mantle structure inside the Earth has mainly relied on the time difference of seismic waves to calculate azimuth‐dependent velocity changes, namely azimuthal anisotropy. Due to the correlation between the direction of maximum velocity propagation and the direction of mantle flow and plate deformation, the study of mantle anisotropy can provide evidence for the evolution of the Earth. However, studying anisotropy based on seismic wave travel time is often affected by heterogeneity, especially in extremely complex structures such as Southern California. The splitting of shear waves can effectively constrain the anisotropy of the mantle in the lateral direction, but its depth resolution is poor. Additional rotational amplitude observations with local sensitivity and depth resolution can provide better constraints on the study of mantle anisotropy, providing new evidence for the direction of mantle flow and plate motion. Key Points: Local seismic anisotropy revealed for the first time from rotational amplitude observationsDepth dependence of anisotropy in the local upper mantle of Southern California region is well resolved in lateral and vertical directionsThe asthenospheric fast axis matches absolute plate motions, providing new insights on geodynamic processes in Southern California [ABSTRACT FROM AUTHOR]

A new approach is proposed for measuring the dispersion relation of surface waves in weakly anisotropic media using a single station, which consists of translational displacement and rotation or strain. The azimuth-dependent surface wave dispersion curve can be directly obtained by using the amplitude ratio of translational displacement to rotation or strain. Using observations from earthquakes from a variety of azimuths allows us to characterize the anisotropy of subsurface media. The amplitude ratio gives the localized azimuth-dependent dispersion relations of the formation beneath a receiver without requiring knowledge of the source or structure along the path. The theory shows that in anisotropic media the coupled quasi-Rayleigh wave and quasi-Love wave will result in elliptically polarized rotational motions. In addition, rotational motion information allows the determination of backazimuth even in general anisotropic media. We carry out numerical experiments, investigate the effects of noise and degree of anisotropy and demonstrate the potential for field studies. [ABSTRACT FROM AUTHOR]

In contrast to the 'community lost' argument describing the changing local social order in urban China, an increasing amount of local civic action is occurring in newly built Chinese commodity housing estates through the application of local social networks and capital, enabling the development of local community life. On the basis of the key themes underlying local civic action, in this study we develop a theoretical framework linking the application and development of local social networks and capital through multiple civic action steps by applying a dichotomised definition of social networks and considering the involvement of multiple stakeholders within China's institutions. In a case study of a newly built Chinese commodity housing estate, we used interviews and questionnaires to identify social changes in the neighbourhood inspired by civic action that promotes place attachment, mutual trust and civic responsibility. The development of local community life is created in a heterogeneous neighbourhood, and the influence of civic action on the local social order is reflected within the Chinese context. This article was published open access under a CC BY licence: https://creativecommons.org/licences/by/4.0. [ABSTRACT FROM AUTHOR]

We develop a novel approach for imaging subsurface lateral heterogeneities using six-component (6C) ambient seismic noise data, consisting of three translational components and three rotational components. We first derive the 6C cross-correlation functions (CCFs) from ambient seismic noise data for surface waves and then apply the modified frequency Bessel (MF-J) transform to the 6C CCFs for surface wave dispersion curves. The phase velocities of Rayleigh and Love waves can be directly calculated from the 6C CCFs of a single pair of stations. Traditional array-based surface wave methods derive the surface wave phase velocity based on the presumption of a horizontally layered model. When this assumption breaks down due to the presence of, for example, dipping layer or heterogeneities, the resulting phase velocity can be severely smeared. By contrast, the proposed approach is not limited by the layered model assumption because it relies on single-point measurements to calculate the localized dispersion relations of the formation right beneath a receiver. Our numerical modelling results demonstrate that this approach is applicable to heterogeneous models and can image small-scale subsurface anomalies with very high lateral resolution. [ABSTRACT FROM AUTHOR]

Background: To report the efficacy and safety data of immunotherapy plus angiogenic inhibitors treatment in lung adenocarcinoma patients. Methods: Eligible patients with pathological or cytological confirmed locally advanced or metastatic lung adenocarcinoma and treated with immune checkpoint inhibitors (ICI) plus angiogenic inhibitors were enrolled. The primary endpoints were progressive free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: A total of 46 consecutive enrolled patients received ICI plus angiogenic inhibitor, and the median follow-up was 9.6 months (range 1.5–32.5). The ORR and DCR were 8.7% (n = 4) and 50% (n = 23), respectively. Median PFS and OS were 2.9 months (95% CI 2.1–3.7) and 12.3 months (95% CI 7.6–17.0), respectively. Patients at stage IVB had an inferior PFS than stage IIIC or IVA (2.8 months vs 4.4 months, P = 0.003). The median PFS of patients who were treated with ICI plus bevacizumab was shorter than ICI plus anlotinib or apatinib (1.2 months vs 3.3 months, P = 0.005). The occurrence of hypertension during the combination treatment has been related to a tendency for prolonged PFS (5.5 months vs 2.6 months; P = 0.05). The overall incidence of treatment-related adverse events (TRAE) was 89.1% (n = 41), and grade 3–4 TRAE was occupied 21.4% (n = 10). Conclusion: This study objectively demonstrated that the treatment of ICI and antiangiogenic agents in lung adenocarcinoma could be a promising alternative therapeutic regimen, and the toxic effects were manageable. Subgroup analysis revealed that small molecular angiogenic inhibitors plus ICI and low tumor burden during treatment were better prognostic factors. [ABSTRACT FROM AUTHOR]

Aim: There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta‐analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. Methods: Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence‐free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. Results: A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p < 0.001) and OS (HR = 2.02, p < 0.001). In subgroup analysis on operation mode, the prognostic value of STAS was prominently shown in patients who underwent limited resection (RFS: HR = 3.58, p < 0.001; OS: HR = 3.37, p < 0.001), while for patients who underwent lobectomy, adverse impact of STAS on RFS was observed (HR = 1.60, p = 0.019), but no significant difference was observed on OS (HR = 1.56, p = 0.061). The results fluctuated in different regions while other factors did not alter the independent predictive value of STAS. Conclusion: Tumor STAS should be considered as an adverse prognostic indicator for patients with stage I lung ADC, especially for those under limited resection. More intensive medical care for those patients needs to be investigated in further studies. [ABSTRACT FROM AUTHOR]

Intra‐tumour immune infiltration is a crucial determinant affecting immunotherapy response in non‐small cell lung cancer (NSCLC). However, its phenotype and related spatial structure have remained elusive. To overcome these restrictions, we undertook a comprehensive study comprising spatial transcriptomic (ST) data (28 712 spots from six samples). We identified two distinct intra‐tumour infiltration patterns: immune exclusion (characterised by myeloid cells) and immune activation (characterised by plasma cells). The immune exclusion and immune activation signatures showed adverse and favourable roles in NSCLC patients' survival, respectively. Notably, CD14+APOE+ cells were recognised as the main cell type in immune exclusion samples, with increased epithelial‒mesenchymal transition and decreased immune activities. The co‐location of CD14+APOE+ cells and MMP7+ tumour cells was observed in both ST and bulk transcriptomics data, validated by multiplex immunofluorescence performed on 20 NSCLC samples. The co‐location area exhibited the upregulation of proliferation‐related pathways and hypoxia activities. This co‐localisation inhibited T‐cell infiltration and the formation of tertiary lymphoid structures. Both CD14+APOE+ cells and MMP7+ tumour cells were associated with worse survival. In an immunotherapy cohort from the ORIENT‐3 clinical trial, NSCLC patients who responded unfavourably exhibited higher infiltration of CD14+APOE+ cells and MMP7+ tumour cells. Within the co‐location area, the MK, SEMA3 and Macrophage migration inhibitory factor (MIF) signalling pathway was most active in cell‒cell communication. This study identified immune exclusion and activation patterns in NSCLC and the co‐location of CD14+APOE+ cells and MMP7+ tumour cells as contributors to immune resistance. [ABSTRACT FROM AUTHOR]

We develop a generalized reflection and transmission coefficient method (GRTM) for generating six-component (6-C) synthetic seismograms in horizontally layered vertically transversely isotropic (VTI) media. Compared with the traditional seismic modelling approaches that only consider translational motion, our method can simultaneously produce three-component translational and three-component rotational data excited by a point vector force or a moment tensor source in a layered half-space. Horizontally layered models are widely used in near surface applications as the properties of near surface formations generally show small lateral variations and change mainly along the depth direction. The use of the VTI constitutive relation can make our method applicable to more general situations because it takes into account the characteristics of sedimentary formations. We compare our method with a finite-difference method (FDM) for a variety of velocity models and acquisition geometries. The numerical results demonstrate that accurate 6-C synthetic seismograms can be calculated using our method. The computational efficiency of our method for 6-C seismic modelling is much higher than the finite-difference method, because it can reduce a 3-D modelling problem to 2.5-D by eliminating the azimuthal dimension. Also, our method does not require to perform additional spatial interpolations to obtain the rotational components. These advantages make our method suitable to serve as a forward modelling tool for rotational seismology. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment. KCNK1 is a potassium channel differentially expressed in many tumors, but the mechanisms underlying its function in breast cancer remain unclear. This study shows that KCNK1 is overexpressed in breast cancer promoting proliferation, invasion and metastasis by increasing glycolysis and activating Lactate Dehydrogenase A. [ABSTRACT FROM AUTHOR]

During embryonic development, one of the two X chromosomes of a mammalian female cell is randomly inactivated by the X chromosome inactivation mechanism, which is mainly dependent on the regulation of the non-coding RNA X-inactive specific transcript at the X chromosome inactivation center. There are three proteins that are essential for X-inactive specific transcript to function properly: scaffold attachment factor-A, lamin B receptor, and SMRT- and HDAC-associated repressor protein. In addition, the absence of X-inactive specific transcript expression promotes tumor development. During the process of chromosome inactivation, some tumor suppressor genes escape inactivation of the X chromosome and thereby continue to play a role in tumor suppression. A well-functioning tumor suppressor gene on the idle X chromosome in women is one of the reasons they have a lower propensity to develop cancer than men, women thereby benefit from this enhanced tumor suppression. This review will explore the mechanism of X chromosome inactivation, discuss the relationship between X chromosome inactivation and tumorigenesis, and consider the consequent sex differences in cancer. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. Methods: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. Results: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. Conclusions: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance makes pathogenic bacteria hard to control, but little is known about the general processes of resistance gain or loss. Here, we compared distinct S. typhimurium DT104 strains resistant to zero, two, five, or more of the tested antimicrobials. We found that common resistance phenotypes could be encoded by distinct genes, on SGI-1 or plasmid. We also demonstrated close clonality among all the tested non-resistant and differently resistant DT104 strains, demonstrating dynamic acquisition or loss (by total deletion or gradual decaying of multi-drug resistance gene clusters) of the genetic traits. These findings reflect convergent processes to make the bacteria resistant to multiple antimicrobials by acquiring the needed traits from stochastically available origins. When the antimicrobial stress is absent, the resistance genes may be dropped off quickly, so the bacteria can save the cost for maintaining unneeded genes. Therefore, this work reiterates the importance of strictly controlled use of antimicrobials. [ABSTRACT FROM AUTHOR]

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of the synthesis of natural products, drugs, and complex compounds. It is anticipated that late-stage functionalization would improve drug discovery's effectiveness and efficiency and hasten the creation of various chemical libraries. Consequently, late-stage functionalization of natural products is a productive technique to produce natural product derivatives, which significantly impacts chemical biology and drug development. Carbon–carbon bonds make up the fundamental framework of organic molecules. Compared with the carbon–carbon bond construction, the carbon–carbon bond activation can directly enable molecular editing (deletion, insertion, or modification of atoms or groups of atoms) and provide a more efficient and accurate synthetic strategy. However, the efficient and selective activation of unstrained carbon–carbon bonds is still one of the most challenging projects in organic synthesis. This review encompasses the strategies employed in recent years for carbon–carbon bond cleavage by explicitly focusing on their applicability in late-stage functionalization. This review expands the current discourse on carbon–carbon bond cleavage in late-stage functionalization reactions by providing a comprehensive overview of the selective cleavage of various types of carbon–carbon bonds. This includes C–C-(sp), C–C-(sp2), and C–C-(sp3) single bonds; carbon–carbon double bonds; and carbon–carbon triple bonds, with a focus on catalysis by transition metals or organocatalysts. Additionally, specific topics, such as ring-opening processes involving carbon–carbon bond cleavage in three-, four-, five-, and six-membered rings, are discussed, and exemplar applications of these techniques are showcased in the context of complex bioactive molecules or drug discovery. This review aims to shed light on recent advancements in the field and propose potential avenues for future research in the realm of late-stage carbon–carbon bond functionalization. [ABSTRACT FROM AUTHOR]

To obtain a new low-cost catalyst that possesses well Hg 0 removal activity in a broad temperature range, a series of Cu-Zr x /Cl-BC catalysts were synthesized with the application of bio-char which was activated by NH 4 Cl. CuO-ZrO 2 as the active component largely improved Hg 0 removal activity of the catalysts. The catalysts were characterized by SEM-EDX, BET, XRD, H 2 -TPR, XPS and FT-IR. When the CuO-ZrO 2 loading value was 10%, Cu-Zr 10 /Cl-BC reached the best Hg 0 removal efficiency (98.87%) at 120 °C and maintained over 80% until 240 °C. O 2 was of benefit to Hg 0 removal process especially at high temperature because it could regenerate the lattice oxygen which participated in the removal reaction. In addition, Hg 0 removal was mainly determined by adsorption at low temperature and the function of oxidation increased at high temperature. The characterization results indicated that the superior performance of Cu-Zr 10 /Cl-BC might be ascribed to lower crystallinity, stronger redox ability and better texture properties which resulted from the interaction of CuO and ZrO 2 . The mechanism for Hg 0 removal over Cu-Zr 10 /Cl-BC was also proposed on the basis of above studies. [ABSTRACT FROM AUTHOR]

In this study, surface-enhanced Raman spectroscopy (SERS) charged probes and an inverted superhydrophobic platform were used to develop a detection method for agricultural chemicals residues (ACRs) in rice combined with lightweight deep learning network. First, positively and negatively charged probes were prepared to adsorb ACRs molecules to SERS substrate. An inverted superhydrophobic platform was prepared to alleviate the coffee ring effect and induce tight self-assembly of nanoparticles for high sensitivity. Chlormequat chloride of 15.5–0.05 mg/L and acephate of 100.2–0.2 mg/L in rice were measured with the relative standard deviation of 4.15% and 6.25%. SqueezeNet were used to develop regression models for the analysis of chlormequat chloride and acephate. And the excellent performances were obtained with the coefficients of determination of prediction of 0.9836 and 0.9826 and root-mean-square errors of prediction of 0.49 and 4.08. Therefore, the proposed method can realize sensitive and accurate detection of ACRs in rice. SERS charged probes and inverted superhydrophobic platform were used to detect chlormequat chloride and acephate in rice. Regression models of chlormequat chloride and acephate were developed using SqueezeNet, and the deconvolution method visualized the feature extraction of SqueezeNet. [Display omitted] • SERS and lightweight deep learning network were used to detect ACRs in rice. • Positively and negatively charged SERS probes were prepared to adsorb ACRs. • Homogeneous hotspot array was self-assembled by inverted superhydrophobic platform. • SqueezeNet was developed for intelligent and accurate analysis of ACRs levels in rice. • Deconvolution method was used to visualize feature extraction of SqueezeNet. [ABSTRACT FROM AUTHOR]

Reflectance spectroscopy was used to detect amylase activity and moisture content in rice with the husk interference removal by spectral data transformation, and the moisture content was added to the analysis model of amylase activity to obtain the improved prediction result. [Display omitted] • Reflectance spectroscopy was used to detect amylase activity and moisture content in rice. • Spectral data transformation was used to remove influence of rice husk. • Random frog and elliptical envelope were used to select effective wavelengths. • Effect of moisture content on analysis of amylase activity was explored. In this study, reflectance spectroscopy was used to achieve rapid and non-destructive detection of amylase activity and moisture content in rice. Since rice husk can interfere with spectral measurements, spectral data transformation was used to remove the husk interference. Reflectance spectra of rice were transformed by direct standardization, convolutional autoencoder network, and kernel regression (KR). Then, random frog and elliptical envelope were adopted to select effective wavelengths, and partial least squares regression (PLSR) and support vector regression were used to establish analysis models. The optimal transformation was from KR, and PLSR and effective wavelengths of the transformed spectra obtained excellent performance with coefficient of determination of test of 0.6987 and 0.8317 and root-mean-square error of test of 0.3359 and 2.2239, respectively. The result was better than that of the rice spectra and was close to that of the husked rice spectra. When the moisture content was integrated into the regression model of amylase activity, a better result was obtained. Thus, the proposed method can detect amylase activity and moisture content in rice accurately. [ABSTRACT FROM AUTHOR]

Background: Observational studies have reported controversial results on the association between obesity and head and neck cancer risk. This study aimed to perform a two-sample Mendelian randomization (MR) analysis to assess the causal association between obesity and head and neck cancer risk using publicly available genome-wide association studies (GWAS) summary statistics. Methods: Single-nucleotide polymorphisms (SNPs) for obesity [body mass index (BMI), waist-to-hip ratio (WHR), whole body fat mass, lean body mass, and trunk fat mass] and head and neck cancer (total head and neck cancer, oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer) were retrieved from published GWASs and used as genetic instrumental variables. Five methods including inverse-variance-weighted (IVW), weighted-median, MR–Egger, weighted mode, and MR-PRESSO were used to obtain reliable results, and odds ratio with 95% confidence interval (CI) were calculated. Tests for horizontal pleiotropy, heterogeneity, and sensitivity were performed separately. Results: Genetically predicted BMI was negatively associated with the risk of total head and neck cancer, which was significant in the IVW [OR (95%CI), 0.990 (0.984–0.996), P = 0.0005], weighted-median [OR (95%CI), 0.984 (0.975–0.993), P = 0.0009], and MR-PRESSO [OR (95%CI), 0.990 (0.984–0.995), P = 0.0004] analyses, but suggestive significant in the MR-Egger [OR (95%CI), 0.9980 (0.9968–0.9991), P < 0.001] and weighted mode [OR (95%CI), 0.9980 (0.9968–0.9991), P < 0.001] analyses. Similar, genetically predicted BMI adjust for smoking may also be negatively associated with the risk of total head and neck cancer (P < 0.05). Genetically predicted BMI may be negatively related to the risk of oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer (P < 0.05), but no causal association was observed for BMI adjust for smoking (P > 0.05). In addition, no causal associations were observed for other exposures and outcomes (all P > 0.05). Conclusion: This MR analysis supported the causal association of BMI-related obesity with decreased risk of total head and neck cancer. However, the effect estimates from the MR analysis were close to 1, suggesting a slight protective effect of BMI-related obesity on head and neck cancer risk. [ABSTRACT FROM AUTHOR]

[Display omitted] • Drugs in human hair were extracted by alkaline hydrolysis and liquid–liquid extraction. • A uniform and sensitive substrate was prepared by inverted evaporation. • Methamphetamine, ketamine, and morphine at 0.05, 0.1, and 0.1 ng/mg can be detected by SERS. • Inception with residual modules achieved best recognition. • Effect of spectral input form on the identification performance was analyzed. Detection of illegal drug users is crucial in controlling drug-related crimes, reducing drug prevalence, and protecting human lives to ensure social stability. In this study, surface-enhanced Raman spectroscopy (SERS) and deep learning networks were employed to determine methamphetamine, ketamine, and morphine in human hair. Drugs were obtained from hair through alkaline hydrolysis and liquid–liquid extraction, and gold nanorods were employed to prepare the self-assembled film as the SERS substrate by inverted evaporation. The film showed good uniformity and excellent sensitivity, with a relative standard deviation of 15.6% and a detection limit of at least 10-10 M in the SERS detection of crystal violet. The spectra of methamphetamine, ketamine, and morphine at 0.05–1.0, 0.1–2.0, and 0.1–2.0 ng/mg were obtained, and the three drugs could be detected. Inception, a multi-scale feature extraction network, was combined with residual modules (Inception–ResNet) to develop the identification models of drugs, and the effect of spectral input form as a vector or matrix was explored. Inception–ResNet with input form of matrix outweighed other methods with 100.00%, 100.00%, and 99.23% accuracies in the training, validation, and prediction sets, respectively. In brief, SERS and Inception–ResNet with the spectra in matrix form provide an efficient and accurate determination of drugs in human hair, enabling the retrospective evaluation of drug use, and the method will be anticipated to detect excitant, poison, and toxic chemicals in human hair. [ABSTRACT FROM AUTHOR]

From multi-substituted 8-aminoimidazo[1,2- a ]pyrazines, prepared via modified Groebke–Blackburn–Bienaymé reaction, a Pd-catalyzed cyclization reaction was discovered, leading to a rare ( Z )-4,5-dihydro-3 H -[1,3]diazocine system. Conditions of this cyclization were screened and DMF solvent was found as one of the key factors for the cyclization. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue with uncertain pathologic mechanism. Neuroimage may be an important key to unveil the central nervous system (CNS) mechanism in CFS. Although most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS, there are many factors that could affect GM volumes in CFS, including chronic pain, stress, psychiatric disorder, physical activity, and insomnia, which may bias the results. In this paper, through reviewing recent literatures, we discussed these interferential factors, which overlap with the symptoms of CFS. [ABSTRACT FROM AUTHOR]

A series of comprehensive reforms and renovations were conducted in the construction of clinical practice teaching system, team huilding, management mode operating mechanism and people-oriented facilities hy taking the construction of the state clinical skiils experimental teaching demonstration center as an opportunity. The experimental teaching philosophy of "one center, two environments three platforms and four requirements" were proposed. The advanced experimental teaching platform for training hasic clinical skiils and thinking were reconstructed. The clinical experiment courses were adjusted and updated according to Clinical Practitioners Practical Skiils Examination Syllahus and Clinical Skiils of Chinese Medical Students Operation Guide. We focused on comhining with simulative and real clinical environment, integrating the clinical skiil training content and exploring a set of clinical skiils training modes that possessed advanced teaching ideas, reasonahle curriculum structure, lifelike simulative environment, and teaching effects feedhack. Many outstanding achievements were made. It is useful as reference to promote development of clinical skiils training center of local comprehensive university. This paper introduced the characteristics of teaching reforms and management mode of clinical skiils training center of Nantong University. [ABSTRACT FROM AUTHOR]

Background: The bacterial genus Salmonella contains thousands of serotypes that infect humans or other hosts, causing mild gastroenteritis to potentially fatal systemic infections in humans. Pathogenically distinct Salmonella serotypes have been classified as individual species or as serological variants of merely one or two species, causing considerable confusion in both research and clinical settings. This situation reflects a long unanswered question regarding whether the Salmonella serotypes exist as discrete genetic clusters (natural species) of organisms or as phenotypic (e.g. pathogenic) variants of a single (or two) natural species with a continuous spectrum of genetic divergence among them. Our recent work, based on genomic sequence divergence analysis, has demonstrated that genetic boundaries exist among Salmonella serotypes, circumscribing them into clear-cut genetic clusters of bacteria. Methodologies/Principal Findings: To further test the genetic boundary concept for delineating Salmonella into clearly defined natural lineages (e.g., species), we sampled a small subset of conserved genomic DNA sequences, i.e., the endonuclease cleavage sites that contain the highly conserved CTAG sequence such as TCTAGA for XbaI. We found that the CTAG-containing cleavage sequence profiles could be used to resolve the genetic boundaries as reliably and efficiently as whole genome sequence comparisons but with enormously reduced requirements for time and resources. Conclusions: Profiling of CTAG sequence subsets reflects genetic boundaries among Salmonella lineages and can delineate these bacteria into discrete natural clusters. [ABSTRACT FROM AUTHOR]

Spread through air spaces (STAS) is a recognized aggressive pattern in lung cancer, serving as a crucial risk factor for postoperative recurrence. However, its phenotype and related spatial structure have remained elusive. To address these limitations, we conducted a comprehensive study based on spatial data, analyzing over 30,000 spots from 14 non-STAS samples and one STAS sample. We observed increased proliferation activities and angiogenesis in STAS, identifying S100P as a potential biomarker for STAS. Furthermore, our investigation into the heterogeneity of STAS tumor cells revealed a subset identified as S100P + TFF1 +, exhibiting a negative impact on patients' survival in public datasets. This subtype exhibited the highest activities in the TGFb and hypoxia, suggesting its potential pro-tumor role within the tumor microenvironment. To assess the role of S100P + TFF1 + tumor cells in therapy response, we included data from two clinical trial cohorts (BPI-7711 for EGFR-TKI therapy and ORIENT-3 for immunotherapy). The presence of S100P + TFF1 + tumor cells correlated with worse responses to both EGFR-TKI therapy and immunotherapy. Notably, TFF1 emerged as a serum marker for predicting EGFR-TKI response. Cell–cell communication analysis revealed that the TGFb signaling pathway was the most activated in S100P + TFF1 + tumor cells, with TGFB2-TGFBR2 identified as the main ligand-receptor pair. This was further validated by multiplex immunofluorescence performed on twenty NSCLC samples. In summary, our study identified S100P as the biomarker for STAS and highlighted the adverse role of S100P + TFF1 + tumor cells in survival outcomes. [ABSTRACT FROM AUTHOR]

Abstract: The deadly human typhoid agent was initially classified as a species called Salmonella typhi but later reclassified as a serovar of Salmonella enterica together with other pathogenically diverse serovars. The dynamic changes of Salmonella taxonomy reflect the need to clarify the phylogenetic status of the Salmonella serovars: are they discrete lineages or variants of a genetic lineage? To answer this question, we compared S. typhi and other Salmonella serotypes. We found that the S. typhi and Salmonella typhimurium strains had over 90% and ca. 80%, respectively, of their genes identical; however, between S. typhi and S. typhimurium, this percentage dropped to 6%, suggesting the existence of genetic boundaries between them. We conclude that S. typhi and the other compared Salmonella serovars have developed into distinct lineages circumscribed by the genetic boundary. This concept and methods may be used to delineate other Salmonella serotypes, many of which are polyphyletic, needing differentiation. [Copyright &y& Elsevier]

In this article, the tube-like nickel oxide materials was synthesized by decomposition of nickel oxalate which was prepared by a facile hydrothermal method. Some experimental parameters affecting the morphology were studied. The electrochemical capacitive properties of the nickel oxide macrotubes were investigated using cycling voltammetry and charge/discharge techniques with KOH as electrolytes. The specific capacitance of the obtained nickel oxide macrotube electrode was measured to be as high as 701.2 F g−1at a current density of 0.5 A g−1. The effect of calcination temperature and current density on the specific capacities were also studied. Furthermore, the obtained nickel oxide shows a good capacitive retention of ca.93% after 1000 charge/discharge cycles. [ABSTRACT FROM AUTHOR]

Objective: Although human umbilical cord-derived mesenchymal stem cells (HU-MSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing, the underlying molecular mechanisms have been poorly understood. It has been shown that the TGF-β/Smad signaling pathway plays an important role in the process of scar formation. The present study focused on exploring whether HU-MSCs improve uterine incision healing after cesarean delivery in rats via the TGF-β/Smad signaling pathway. Study Design: Pregnant rats were randomly assigned to three groups, including the NP group, incision-injected group (HU-MSCs1 group), and tail vein-injected group (HU-MSCs2 group), and 30 days after cesarean section, sampling was carried out to further explore the specific mechanisms from tissue and protein levels. Results: HU-MSCs secretion could inhibit the fibrosis of scar tissue. We observed that the TGF-β induced expression of TGF-β1, Smad2, and Smad3 was attenuated upon HU-MSCs treatment in scar tissue, while the decrease in TGF-β3 expression was enhanced by HU-MSCs. Furthermore, HU-MSCs treatment accelerated wound healing and attenuated collagen deposition in a damaged uterine rat model, leading to the promoting of uterine incision scarring. In addition, the expression of alpha-smooth muscle actin (a-SMA) was enhanced by HU-MSCs treatment. Conclusion: HU-MSCs transplantation promotes rat cesarean section uterine incision scar healing by modulating the TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

The prevalence of severe mental disorders has been rising annually. Electroconvulsive therapy (ECT) is considered a valuable treatment option in psychiatry for conditions such as schizophrenia and medication-resistant depression, especially when other treatments have proven insufficient. ECT rapidly improves patients' mood, alleviates symptoms, and demonstrates significant therapeutic effects. Currently, the form of ECT used in clinical practice is modified electroconvulsive therapy (mECT), which is administered under general anesthesia. Accumulative evidence has confirmed that different anesthetic drugs, anesthetic-ECT time interval, anesthetic depth, and airway management can impact the outcomes of ECT. Therefore, this review aims to summarize the current impact of anesthesia factors on ECT, providing reference for clinical anesthesia during ECT procedures. [ABSTRACT FROM AUTHOR]

Introduction: Identifying new biomarkers for predicting immune checkpoint inhibitors (ICIs) response in non-small cell lung cancer (NSCLC) is crucial. We aimed to assess the variant allele frequency (VAF)-related profile as a novel biomarker for NSCLC personalized therapy. Methods: We utilized genomic data of 915 NSCLC patients via cBioPortal and a local cohort of 23 patients for model construction and mutational analysis. Genomic, transcriptomic data from 952 TCGA NSCLC patients, and immunofluorescence (IF) assessment with the local cohort supported mechanism analysis. Results: Utilizing the random forest algorithm, a 15-gene VAF-related model was established, differentiating patients with durable clinical benefit (DCB) from no durable benefit (NDB). The model demonstrated robust performance, with ROC-AUC values of 0.905, 0.737, and 0.711 across training (n = 313), internal validation (n = 133), and external validation (n = 157) cohorts. Stratification by the model into high- and low-score groups correlated significantly with both progression-free survival (PFS) (training: P < 0.0001, internal validation: P < 0.0001, external validation: P = 0.0066) and overall survival (OS) (n = 341) (P < 0.0001). Notably, the stratification system was independent of PD-L1 (P < 0.0001) and TMB (P < 0.0001). High-score patients exhibited an increased DCB ratio and longer PFS across both PD-L1 and TMB subgroups. Additionally, the high-score group appeared influenced by tobacco exposure, with activated DNA damage response pathways. Whereas, immune/inflammation-related pathways were enriched in the low-score group. Tumor immune microenvironment analyses revealed higher proportions of exhausted/effector memory CD8 + T cells in the high-score group. Conclusions: The mutational VAF profile is a promising biomarker for ICI therapy in NSCLC, with enhanced therapeutic stratification and management as a supplement to PD-L1 or TMB. [ABSTRACT FROM AUTHOR]

Presents a study on voltage flicker prediction for two simultaneously operated AC ARC furnaces. Flicker sensitivity curve showing limits for voltage fluctuations as a function of their frequency of occurrence; Furnace load; Typical waveforms.

Describes the techniques used to measure, analyze and simulate the problems associated with the use of pulsewidth modulation (PWM) adjustable speed drive's (ASD) to drive induction motors. Output of the PWM drive; Most harmful effect of the PWM ASD; Model development and validation; Evaluation of mitigation methods; Design-related issues; Conclusions.

A combination of mesoscale simulations and explosive loading experiments is used to investigate the shock response and shock-induced initiation behavior of aluminum-polytetrafluoroethylene (Al-PTFE) granular composites. A two-dimensional model following the random distribution of real Al particle sizes is developed and validated against experiments. The model is employed to investigate the effect of Al mass fractions on shock characterizes as well as Hugoniot relationships, and noticeable differences are visualized at the grain-level in the pressure, temperature, and strain response. Systematic shock structures in metals have been identified, and the underlying mechanisms of deformation and energy dissipation are discussed respectively. Results demonstrate that the high pressure is concentrated in the wave front, but a much greater heat and larger strain exhibit along grain/matrix interfaces that enable the friction dissipation the main mechanism of hot-spots formation. Specific quantities of critical temperature to initiate are obtained based on basic microstructure attributes to analyze the influence on hot-spots distribution by mass fractions. The interaction of shock wave with mesoscale heterogeneities accounts for the stochastic nature of the initiation process. Unlabelled Image • Mesoscale simulation combined with explosive loading tests is employed. • Grain-level mechanical, thermal responses, and Hugoniot relationships are obtained. • Plastic deformation and particle/particle friction lead to hot-spots. • Hot-spots distribution reveals the stochastic nature of the initiation process. [ABSTRACT FROM AUTHOR]

Background: R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. Methods: Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high‐density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL‐focused microarray, comparative results based on event‐free survival at 24 months (EFS24) and lasso Cox regression models of progression‐free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme‐linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two‐AAb‐based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598). Results: Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p <.05) and superior PFS and OS (p <.05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R‐CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p <.05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p <.05). Conclusions: This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL. Autoantibodies (AAbs) have the potential for personalized monitoring of tumor recurrence. Serological AAbs against N4BP1, CREB1, DEAF1, and UBAP2 were independent of International Prognostic Index traditional risk factors for diffuse large B‐cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Notably, two of these biomarkers, CREB1 and N4BP1, exhibited prognostic significance at multiple levels, including messenger RNA, protein, and AAb. These findings suggest that monitoring AAb levels during treatment may be a useful tool for predicting prognosis and guiding personalized treatment strategies for patients with DLBCL. [ABSTRACT FROM AUTHOR]

The response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays. Differential proteomic characteristics in responders (R) and non-responders (NR) before and after anti-PD1 therapy were elucidated. A total of 1019 proteins were detected using our in-depth proteomics platform and distributed across 10–12 orders of abundance. By comparing the differential plasma proteome expression between R and NR groups, 50, 206, and 268 proteins were identified in NSCLC, ASPS, and lymphoma patients, respectively. Th17, IL-17, and JAK-STAT signal pathways were identified upregulated in NR group, while cellular senescence and transcriptional misregulation pathways were activated in R group. Longitudinal proteomics analysis revealed the IL-17 signaling pathway was downregulated after treatment. Consistently, many proteins were identified as potential combinatorial therapeutic targets (e.g., IL-17A and CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, and IL-17A) were further validated in an independent lymphoma cohort (n = 39), and another three noninvasive biomarkers (KIT, CCL3, and TNFSF1) were validated in NSCLC cohort (n = 76). Our results provide molecular insights into the anti-PD1 therapy in cancer patients and identify new therapeutic strategies for anti-PD1-resistant patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop and validate a novel risk stratification model and a web-based survival rate calculator to improve discriminative and predictive accuracy for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methods: We retrospectively collected pre-treatment data from 873 primary DLBCL patients who received R-CHOP-based immunochemotherapy regimens at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 1, 2005, to December 31, 2018. An independent cohort of 175 DLBCL patients from Fujian Cancer Hospital was used for external validation. Findings: Age, ECOG PS, number of extranodal sites, Ann Arbor stage, bulky disease, and LDH levels were screened to develop the nomogram and web-based survival rate calculator. The C-index of the nomogram in the training, internal validation, and external validation cohorts was 0.761, 0.758, and 0.768, respectively. The risk stratification model generated based on the nomogram effectively stratified patients into three distinct risk groups. K-M survival curves demonstrated that the novel risk stratification model exhibited a superior level of predictive accuracy compared to IPI, R-IPI, and NCCN-IPI both in training and two validation cohorts. Additionally, the area under the curve (AUC) value of the novel model (0.763) for predicting 5-year overall survival rates was higher than those of IPI (0.749), R-IPI (0.725), and NCCN-IPI (0.727) in the training cohort. Similar results were observed in both internal and external validation cohort. Conclusions: In conclusion, we have successfully developed and validated a novel risk stratification model and a web-based survival rate calculator that demonstrated superior discriminative and predictive accuracy compared to IPI, R-IPI, and NCCN-IPI in the rituximab era. [ABSTRACT FROM AUTHOR]

Tiliroside, a natural flavonoid, has various biological activities and improves several inflammatory diseases in rodents. However, the effect of Tiliroside on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and the underlying mechanisms are still unclear. This study aimed to evaluate the potential renoprotective effect of Tiliroside on LPS-induced AKI in mice. Male C57BL/6 mice were intraperitoneally injected with LPS (a single dose, 3 mg/kg) with or without Tiliroside (50 or 200 mg/kg/day for 8 days). Tiliroside administration protected against LPS-induced AKI, as reflected by ameliorated renal dysfunction and histological alterations. LPS-stimulated renal expression of inflammatory cytokines, fibrosis markers, and kidney injury markers in mice was significantly abolished by Tiliroside. This flavonoid also stimulated autophagy flux but inhibited oxidative stress and tubular cell apoptosis in kidneys from LPS-injected mice. Mechanistically, our study showed the regulation of Tiliroside on the intrarenal renin-angiotensin system in LPS-induced AKI mice. Tiliroside treatment suppressed intrarenal AGT, Renin, ACE, and Ang II, but upregulated intrarenal ACE2 and Ang1-7, without affecting plasma Ang II and Ang1-7 levels. Collectively, our data highlight the renoprotective action of Tiliroside on LPS-induced AKI by suppressing inflammation, oxidative stress, and tubular cell apoptosis and activating autophagy flux via the shift towards the intrarenal ACE2/Ang1-7 axis and away from the intrarenal ACE/Ang II axis. [ABSTRACT FROM AUTHOR]

Background: Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation. Main body: Here, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways. Short conclusion: The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Antigen-presenting cells (APC)/T/NK cells are key immune cells that play crucial roles in fighting against malignancies including lung adenocarcinoma (LUAD). In this study, we aimed to identify an APC/T/NK cells-related gene signature (ATNKGS) and potential immune cell-related genes (IRGs) to realize risk stratification, prognosis, and immunotherapeutic response prediction for LUAD patients. Methods: Based on the univariate Cox regression and the LASSO Cox regression results of 196 APC/T/NK cells-related genes collected from three pathways in the KEGG database, we determined the final genes and established the ATNKGS-related risk model. The single-cell RNA sequencing data were applied for key IRGs identification and investigate their value in immunotherapeutic response prediction. Several GEO datasets and an external immunotherapy cohort from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were applied for validation. Results: In this study, nine independent public datasets including 1108 patients were enrolled. An ATNKGS containing 16 genes for predicting overall survival of LUAD patients was constructed with robust prognostic capability. The ATNKGS high risk group was related to significantly worse OS outcomes than those in the low-risk group, which were verified in TCGA and four GEO datatsets. A nomogram combining the ATNKGS risk score with clinical TNM stage achieved the optimal prediction performance. The single-cell RNA sequencing analysis revealed CTSL as an IRG of macrophage and monocyte. Moreover, though CTSL was an indicator for poor prognosis of LUAD patients, CTSL high expression group was associated with higher ESTIMATEScore, immune checkpoints expression, and lower TIDE score. Several immunotherapeutic cohorts have confirmed the response-predicting significance of CTSL in patients receiving immune checkpoint inhibitor (ICI) treatment. Conclusions: Our study provided an insight into the significant role of APC/T/NK cells-related genes in survival risk stratification and CTSL in response prediction of immunotherapy in patients with LUAD. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. Methods: DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. Results: A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P < 0.001), PIM1 mutation (71% vs. 39%, P < 0.001), and PIM1 hypermutation (28% vs. 11%, P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). Conclusion: The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to explore the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with non‐small cell lung cancer (NSCLC). Methods: Studies that enrolled NSCLC patients treated with two lines of ICIs were included using four databases. The initial line (1L‐) and subsequent lines (2L‐) of ICIs were defined as 1L‐ICI and 2L‐ICI, respectively. Results: A total of 17 studies involving 2100 patients were included. The pooled objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), and median overall survival (mOS) for 2L‐ICIs were 10%, 50%, 3.0 months, and 13.1 months, respectively. The 2L‐ICI discontinuation rates caused by toxicities ranged from 0% to 23.5%. Original data were extracted from six studies, covering 89 patients. Patients in whom 1L‐ICIs were discontinued following clinical decision (the mPFS of 2L‐ICIs was not reach) achieved a more prolonged mPFS of 2L‐ICIs than those due to toxicity (5.2 months) and progressive disease (2.1 months) (p < 0.0001). Patients' 1L‐PFS for more than 2‐years had preferable 2L‐ORR (35.0% vs. 9.8%, p = 0.03), 2L‐DCR (85.0% vs. 49.0%, p = 0.007), and 2L‐mPFS (12.4 vs. 3.0 months, p < 0.0001) than those less than 1‐year. Patients administered the same drugs achieved a significantly prolonged mPFS compared with the remaining patients (5.4 vs. 2.3 months, p = 0.0004), and those who did not accept antitumor treatments during the intervals of two lines of ICIs achieved a prolonged mPFS compared to those patients who did accept treatments (7.6 vs. 1.9 months, p < 0.0001). Conclusions: ICI rechallenge is a useful therapeutic strategy for NSCLC patients, especially suitable for those who achieve long‐term tumor remission for more than 2‐years under 1L‐ICIs. [ABSTRACT FROM AUTHOR]

Highly conserved short sequences help identify functional genomic regions and facilitate genomic annotation. We used Salmonella as the model to search the genome for evolutionarily conserved regions and focused on the tetranucleotide sequence CTAG for its potentially important functions. In Salmonella, CTAG is highly conserved across the lineages and large numbers of CTAG-containing short sequences fall in intergenic regions, strongly indicating their biological importance. Computer modeling demonstrated stable stem-loop structures in some of the CTAG-containing intergenic regions, and substitution of a nucleotide of the CTAG sequence would radically rearrange the free energy and disrupt the structure. The postulated degeneration of CTAG takes distinct patterns among Salmonella lineages and provides novel information about genomic divergence and evolution of these bacterial pathogens. Comparison of the vertically and horizontally transmitted genomic segments showed different CTAG distribution landscapes, with the genome amelioration process to remove CTAG taking place inward from both terminals of the horizontally acquired segment. [ABSTRACT FROM AUTHOR]

Multi-substituted 8-aminoimidazo[1,2-a]pyrazine substrates (I) efficiently prepared by a modified Groebke-Blackburn-Bienayme reaction, undergo a Pd-catalyzed cyclization to form the rare (Z)-4,5-dihydro-3H-[1,3]diazocine system. [ABSTRACT FROM AUTHOR]

Background: Bactericidal/Permeability-increasing-fold-containing family B member 1 (BPIFB1, previously termed LPLUNC1) is highly expressed in the nasopharynx, significantly downregulated in nasopharyngeal carcinoma (NPC), and associated with prognosis in NPC patients. Because metastasis represents the primary cause of NPC-related death, we explored the role of BPIFB1 in NPC migration and invasion.Methods: The role of BPIFB1 in NPC metastasis was investigated in vitro and in vivo. A co-immunoprecipitation assay coupled with mass spectrometry was used to identify BPIFB1-binding proteins. Additionally, western blotting, immunofluorescence, and immunohistochemistry allowed assessment of the molecular mechanisms associated with BPIFB1-specific metastatic inhibition via vitronectin (VTN) and vimentin (VIM) interactions.Results: Our results showed that BPIFB1 expression markedly inhibited NPC cell migration, invasion, and lung-metastatic abilities. Additionally, identification of two BPIFB1-interacting proteins, VTN and VIM, showed that BPIFB1 reduced VTN expression and the formation of a VTN-integrin αV complex in NPC cells, leading to inhibition of the FAK/Src/ERK signalling pathway. Moreover, BPIFB1 attenuated NPC cell migration and invasion by inhibiting VTN- or VIM-induced epithelial-mesenchymal transition.Conclusions: This study represents the first demonstration of BPIFB1 function in NPC migration, invasion, and lung metastasis. Our findings indicate that re-expression of BPIFB1 might represent a useful strategy for preventing and treating NPC. [ABSTRACT FROM AUTHOR]

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. Methods: Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. Results: The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system. Conclusions: Based on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification. [ABSTRACT FROM AUTHOR]

Semiconductiong polymer nanoparticles (Pdots) have a wide range of applications in biomedical fields including biomolecular probes, tumor imaging, and therapy. However, there are few systematic studies on the biological effects and biocompatibility of Pdots in vitro and in vivo. The physicochemical properties of Pdots, such as surface modification, are very important in biomedical applications. Focusing on the central issue of the biological effects of Pdots, we systematically investigated the biological effects and biocompatibility of Pdots with different surface modifications and revealed the interactions between Pdots and organisms at the cellular and animal levels. The surfaces of Pdots were modified with different functional groups, including thiol, carboxyl, and amino groups, named Pdots@SH, Pdots@COOH, and Pdots@NH2, respectively. Extracellular studies showed that the modification of sulfhydryl, carboxyl, and amino groups had no significant effect on the physicochemical properties of Pdots, except that the amino modification affected the stability of Pdots to a certain extent. At the cellular level, Pdots@NH2 reduced cellular uptake capacity and increased cytotoxicity due to their instability in solution. At the in vivo level, the body circulation and metabolic clearance of Pdots@SH and Pdots@COOH were superior to those of Pdots@NH2. The four kinds of Pdots had no obvious effect on the blood indexes of mice and histopathological lesions in the main tissues and organs. This study provides important data for the biological effects and safety assessment of Pdots with different surface modifications, which pave the way for their potential biomedical applications. [ABSTRACT FROM AUTHOR]

Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2- a ]pyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin. [ABSTRACT FROM AUTHOR]