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Abstract Objective Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI. Methods Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained. Results There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P 0.05). Conclusion First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.

In this work, Mg–7Y–5Zn-0.1V alloys were prepared by 1-D forging followed by multi-step rolling. The rolling reduction dependence of the microstructure and tensile properties of the Mg–7Y–5Zn-0.1V alloy was experimentally investigated. The results indicated that the bimodal matrix microstructures are formed, and the fibrous 18R long-period stacking ordered (LPSO) phase and kinked 14H-LPSO phase are observed after 1-D forging. As the rolling deformation increased, the fibrous 18R-LPSO fractured into block and distributed more homogeneous. The lamellar 14H-LPSO fractured more severely, and it re-precipitated within the matrix when the deformation reached 50 %. The average grain size decreased gradually with increasing rolling deformation, and the minimum was 5.07 μm. After rolling, the {0001} and {0001} textures disappeared. The grain refinement of rolling alloy was mainly due to the fact that dynamic recrystallization (DRX) and substructures were generated within some grains, while the forging alloy was mainly due to DRX. The mechanisms of DRX were discontinuous DRX (DDRX) and twin-induced DRX (TDRX) after forging, and continuous DRX (CDRX) and DDRX after rolling. The strength reached its maximum when the rolling deformation amount reached 60 %, with a yield strength (YS) of 350 MPa and an ultimate tensile strength (UTS) of 385 MPa. Compared to the as-cast Mg–7Y–5Zn-0.1V alloy, its strength increased by 56 % and 63 %, respectively. The improvement of mechanical properties was mainly attributed to fine grain strengthening and dislocation strengthening.

Inflammatory cytokines are known to be involved in acute ischemic stroke (AIS), while the relationship of multiple inflammatory cytokines with mental disorders in AIS is less reported. This research intended to explore the longitudinal variation of common inflammatory cytokines and their correlation with anxiety, depression, and cognitive impairment in AIS patients. Six inflammatory cytokines were detected by enzyme-linked immunosorbent assay among 175 AIS patients at admission (baseline) and on the day (D)1, D3, and D7 after admission. Anxiety, depression, and cognition were evaluated using the Hospital Anxiety and Depression Scale and Mini-Mental State Examination at discharge, respectively. Anxiety, depression, and cognitive impairment rates were 32.6, 39.4, and 19.4%, respectively. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17A increased from baseline to D1, then decreased from D1 to D7 (all P

In this paper, the electron backscatter diffraction (EBSD) technique was used to analyze the dynamic recrystallization (DRX), twinning, slip behavior, and texture evolution during forging and subsequent extruding deformation. The results show that, as the degree of strain increased (forging to extruding), the degree of DRX increased, and the DRX mechanism changed from discontinuous DRX (DDRX) during forging to DDRX and continuous DRX (CDRX) during extruding. Particle stimulation nucleation (PSN) promoting DRX occurred during deformation. The deformation process mainly produced {10–12} twins (TTW) and played a role in coordinating the deformation. The slip behavior also changed according to an analysis of in-grain misorientation axes (IGMA) results, changing from slip-dominated with a basal slip to co-dominated with multiple slip modes, with the activation of mainly prismatic and pyramidal slip. Meanwhile, the strong basal texture at the beginning of the deformation also changed, and the texture strength decreased from 24.81 to 15.56. The weakening of the texture was mainly due to the formation of DRX grains and twins, as the newly formed DRX and twins reoriented. In the later stages of deformation, the activation of prismatic slip and pyramidal slip changed the basal texture component. Based on microstructural analysis, the improvement in mechanical properties was due to fine-grain strengthening and load-transfer strengthening. The ultimate tensile strength (UTS) was 370.5 MPa, the yield strength (YS) was 340.1 MPa, and the elongation (EL) was 15.6%.

Abstract Refractive surgery is recognized as an effective method for myopia treatment, but it can induce night vision disturbances such as glare. We present an eye modeling method for the optical quality assessment in response to the structural changes in the eyes by femto-LASIK surgery. Customized eye models were built from the measurements of 134 right eyes pre- and post-operatively. Optical performance was evaluated using spot diagrams, point spread functions (PSFs), modulation transfer functions (MTFs), and chromatic aberrations at various fields (0°–30°), different pupil diameters (2–6 mm), and initial myopias (− 1.25 to − 10.5 D). Pupil size and initial myopia are the two major factors that affect visual performance of post-operative eyes. The results of spot diagrams, PSFs, and MTFs indicated that post-operative visual performance deteriorated as the visual field and pupil size increased, and it was significantly influenced by initial myopia. Post-operative chromatic aberrations were also affected by initial myopia. As pupil size increased, the post-operative longitudinal chromatic aberrations tended to decrease slightly, while the transverse chromatic aberrations remained similar. The use of eye modeling for refractive surgery assessment could possibly provide a more personalized surgical approach, could improve the prediction accuracy of refractive surgery outcomes, and promote the invention and development of better surgical methods.

Death due to acute alcohol poisoning lacks specific anatomical characteristics, compared with other deaths due to drug poisoning. We report three forensic cases of death from acute alcohol poisoning due to inhibition of the respiratory centre and eventual asphyxia. Blood alcohol concentrations in the three fatalities were 5.28, 3.33 and 3.78 mg/mL, respectively. Lethal doses and blood alcohol concentrations showed differences between individuals. Detailed auxiliary tests besides autopsy were undertaken. These cases show that forensic scientists should exclude other causes of death, combine the autopsy with auxiliary tests, and then make an appraisal.

Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60–85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.

Abstract Background Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined. Methods Patients with DMARD-naïve RA enrolled in the “Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis” (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently. Results Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups. Conclusions During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA. Trial registration This is a follow-up study. Original trial registration: ClinicalTrials.gov, NCT01613079. Registered on 4 June 2012.

Bosmina is a globally distributed zooplankton that adapts to a eutrophic environment. In this study, we cultivated monoclonal Bosmina fatalis and determined its complete mitochondrial gene sequence using the Illumina HiSeq 4000 platform. It was 15,209 bp in length, including 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes, with the A + T content (69.2%) significantly higher than the G + C content (30.9%). All 22 typical tRNA genes had a classical cloverleaf structure, except for tRNAIle. The complete mitochondrial genome of nine other cladoceran species was used to reconstruct a phylogenetic tree, showing that B. fatalis has a closer relationship with Daphnia than other cladocerans.

Covalent organic frameworks(COFs) are a kind of porous materials with good crystalline and periodic structure formed by covalent bonding of monomers composed of C, H, O and other light elements. This kind of material shows great application potential in separation, energy storage, catalysis and other aspects because of its low density, high thermal stability and good chemical stability. In recent years, COFs materials have developed a variety of bonding bonds with different structures and characteristics from the initial boron-oxygen bonding bonds, and the most widely studied and in-depth class of COFs materials in these fields are composed of imine-like bonds. Imine-like bond is a class of imine bond derived from Schiff base reaction and its similar structure, which not only contains the advantages of imine bond, but also solves some potential application disadvantages. In recent years, the rapid development of nuclear energy has inevitably brought about the shortage of nuclear resources and environmental radioactive pollution, and how to extract and separate radionuclides has become a major problem to be solved urgently. Among the porous materials that have been developed and explored, COFs has its unique advantages compared with other inorganic porous materials, which can effectively avoid many application difficulties in the process of radionuclide extraction. As the most popular research object in the field of this material, imine-like COFs have been applied in the separation of actinides, especially in the adsorption separation of uranyl ions, which is of great significance to the nuclear fuel cycle and the prevention and control of nuclear environmental pollution. In this paper, the recent progress in the separation and detection of actinide elements by imine-like COFs is summarized, and the characteristics of imine-like bonds with different structures are described in detail. The adsorption mechanism and adsorption effect of COFs materials of each structure are summarized and compared in tables, showing how the design ideas affect the adsorption results, which is instructive for the selection of application scenarios to a certain extent. In addition, some new directions and thoughts on the material are proposed in this paper, which are reliable and forward-looking for improving the potential of imine-like COFs in practical applications. At the same time, the major challenges facing the material are summarized. COFs materials still show unfathomable development potential after decades of in-depth research, and fully demonstrate the urgent development space of this kind of materials in the separation of metal ions. Finally, the future development trend of this material is prospected.

Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. Results showed CD40-induced NF-κB signaling was constitutively activated in B cells from active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IκBα, phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further phosphorylation and degradation of IκBα, as well as phosphorylation of P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of tonsil B cells, in that IKKα/β were more activated compared to normal B cells. CD40-induced NF-κB activity was blocked by both IκB phosphorylation and proteosome degradation inhibitors in both lupus and normal B cells. All together, our findings revealed that canonical NF-κB signaling is constitutively activated in active lupus and is mediated by CD154/CD40. CD40 induced NF-κB activation is different in human lupus B lymphocytes compared with normal B cells.

Pure tungsten (W) was irradiated by low-energy deuterium (D) at 335 and 500 K to investigate the effects of irradiation temperature on the concentration depth profiles (CDPs) of D-induced trapping sites and the retention behavior of D at these trapping sites. To quantify typical D trapping sites, a novel approach was developed by combining experimental and theoretical analysis, including the sequential constant temperature thermal desorption to fast release D from irradiated W, in-situ ion beam analysis to obtain CDPs of retained D after desorption, and a one-dimensional diffusion model to simulate the diffusion, trapping and detrapping of D during desorption. The approach was verified through the microstructural characterization of irradiated W. It was revealed that the retentions of D in both near-surface and sub-surface layers were larger at the lower irradiation temperature (335 K) because of a higher density of D-induced dislocations and cavities in the corresponding regions. Employing the approach, the releasing behavior of D at four typical trapping sites, i.e. dislocations, mono-vacancies, grain boundaries and cavities was quantitatively analyzed. The approach with the capability to quantify typical D trapping sites provides a powerful tool for understanding the retention mechanism of D in the damaged W.

Traditional electrorefining process is limited by deposition potential of the metal itself. Here, the authors explore an in-situ anodic precipitation process based on different solubility of target metal chlorides that can efficiently separate components of aluminum alloys.

Inter-metalloid clusters in Zintl chemistry have been extensively studied due to their unique electronic structures and potential applications. In this work, we explored a series of actinide endohedral inter-metalloid clusters of the group 15 elements [An@Bi12]4− (An = Th–U) and [An@Sb12]4− using density functional theory (DFT). [Th@Bi12]4− and [U@Bi12]4− exhibit Cs symmetry, while [Pa@Bi12]4− and [An@Sb12]4− (An = Th–U) have C1 structures. Bonding analyses such as bond order, molecular orbitals (MO) and quantum theory of atoms in molecules (QTAIM) show covalent An–Bi/An–Sb bonding in the clusters. All these clusters are highly stable according to the studied formation reactions and may be accessible experimentally. Compared with [An@Bi12]4−, [An@Sb12]4− possesses stronger bonding interactions, mainly arising from the higher electrostatic interaction energy. For clusters with the same group 15 elements, the bonding interactions increase gradually from Th to U, which is mainly determined by the covalent interactions of An–Bi/An–Sb bonding. This work is expected to provide potential avenues for the construction of robust inter-metalloid clusters of the group 15 elements. [ABSTRACT FROM AUTHOR]

Efficient anion recognition and trapping is of great significance for anion-specific separation processes but the design of an anion-adaptive sorbents remains a challenge. Here the authors use a cucurbit[8]uril based soft cationic supramolecular material as efficient sorbent for TcO4 − ions.

One hallmark of Guillain-Barre syndrome (GBS), a prototypic autoimmune peripheral neuropathy (APN) is infiltration of leukocytes (macrophages and T cells) into peripheral nerves, where chemokines and their receptors play major roles. In this study, we aimed to understand the potential contribution of chemokine receptors CCR2 and CX3CR1 in APN by using a well-established mouse model, B7.2 transgenic (L31) mice, which possesses a predisposed inflammatory background. We crossbred respectively CCR2KO and CX3CR1KO mice with L31 mice. The disease was initiated by partial ligation on one of the sciatic nerves. APN pathology and neurological function were evaluated on the other non-ligated sciatic nerve/limb. Our results revealed that L31/CX3CR1KO but not L31/CCR2KO mice were resistant to APN. CX3CR1 is needed for maintaining circulating monocyte and CD8+ T cell survival. While migration of a significant number of activated CD8+ T cells to peripheral nerves is essential in autoimmune response in nerve, recruitment of monocytes into PNS seems optional. Disease onset is independent of CCR2 mediated blood-derived macrophage recruitment, which can be replaced by compensatory proliferation of resident macrophages in peripheral nerve. CX3CR1 could also contribute to APN via its critical involvement in maintaining nerve macrophage phagocytic ability. We conclude that blockade of CX3CR1 signaling may represent an interesting anti-inflammatory strategy to improve therapeutic management for GBS patients.

Separation of lanthanide (Ln) and minor actinide (MA) elements and mutual separation between minor actinide elements (e.g. Am(III) and Cm(III)) represent a crucial undertaking. However, separating these elements poses a significant challenge owing to their highly similar physicochemical properties. Asymmetric N-heterocyclic ligands such as N-ethyl-6-(1H-pyrazol-3-yl)-N-(p-tolyl)picolinamide (Et-p-Tol-A-PzPy) and N-ethyl-N-(p-tolyl)-1,10-phenanthroline-2-carboxamide (ETPhenAm) have recently received considerable attention in the separation of MAs over Ln from acid solutions. By changing the central skeleton structures of these ligands and introducing substituents with different properties on the side chains, their complexation behavior with Am(III), Cm(III), and Eu(III) may be affected. In this work, we explore four different asymmetric N-containing heterocyclic ligands, namely Et-p-Tol-A-PzPy (L¹), N-ethyl-6'-(1H-pyrazol-3-yl)-N-(p-tolyl)-[2,2'-bipyridine]-6-carboxamide (L²), N-ethyl-9-(1H-pyrazol-3-yl)-N-(ptolyl)-1,10-phenanthroline-2-carboxamide (L³), and ETPhenAm (L4) using density functional theory (DFT). The calculated results demonstrate the potential of ligands L¹-L4 for the extraction and separation of Am(III), Cm(III), and Eu(III). Ligand analysis shows that ligand L³ binds more easily to the central metal atom, in line with the stronger extraction capacity of L³. In spite of the higher covalence between the side chain and the central metal atom for complexes with L¹-L³, the main chain seems to control the stability of the extraction complexes. The preorganized 1,10-phenanthroline backbone also further enhances the extraction performance of L³ and L4. The difference in coordination ability between the side chain donors of these ligands and metal ions may affect their separation efficiency. This work presents theoretical insights into synthesizing novel ligands for separating trivalent actinides by adjusting N-heterocyclic ligands. [ABSTRACT FROM AUTHOR]

Uncertainties existing in the process of dam deformation negatively influence deformation prediction. However, existing deformation prediction models seldom consider uncertainties. In this study, a cloud-Verhulst hybrid prediction model was established by combing a cloud model with the Verhulst model. The expectation, one of the cloud characteristic parameters, was obtained using the Verhulst model, and the other two cloud characteristic parameters, entropy and hyper-entropy, were calculated by introducing inertia weight. The hybrid prediction model was used to predict the dam deformation in a hydroelectric project. Comparison of the prediction results of the hybrid prediction model with those of a traditional statistical model and the monitoring values shows that the proposed model has higher prediction accuracy than the traditional statistical model. It provides a new approach to predicting dam deformation under uncertain conditions. Keywords: Dam deformation prediction, Cloud model, Verhulst model, Uncertainty, Inertia weight

Abstract Parkinson’s disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P