Author Correction: c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.

Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44- ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORγt, enabling the conversion into IL-17-producing cells in response to IL-1ß and IL-23. We also report a role for transforming growth factor-ß in promoting the conversion of c-Kit- ILC2s into RORγt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORγt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORγt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.

Methylseleninic acid inhibits human glioma growth in vitro and in vivo by triggering ROS-dependent oxidative damage and apoptosis.

Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.

Finite element biomechanical analysis of 3D printed intervertebral fusion cage in osteoporotic population.

OBJECTIVE: To study the biomechanical characteristics of each tissue structure when using different 3D printing Cage in osteoporotic patients undergoing interbody fusion. METHODS: A finite element model of the lumbar spine was reconstructed and validated with regarding a range of motion and intervertebral disc pressure from previous in vitro studies. Cage and pedicle screws were implanted and part of the lamina, spinous process, and facet joints were removed in the L4/5 segment of the validated mode to simulate interbody fusion. A 280 N follower load and 7.5 N·m moment were applied to different postoperative models and intact osteoporotic model to simulate lumbar motion. The biomechanical characteristics of different models were evaluated by calculating and analyzing the range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment. RESULTS: After rigid fixation, the range of motion of the fixed segment of model A-C decreased significantly, which was much smaller than that of the osteoporotic model. And with the increase of the axial area of the interbody fusion cages, the fixed segment of model A-C tended to be more stable. The range of motion and intradiscal pressure of the spinal models with different interbody fusion cages were higher than those of the complete osteoporosis model, but there was no significant difference between the postoperative models. On the other hand, the L5 upper endplate stress and screw-rod system stress of model A-C show a decreasing trend in different directions of motion. The stress of the endplate is the highest during flexion, which can reach 40.5 MPa (model A). The difference in endplate stress between models A-C was the largest during lateral bending. The endplate stress of models A and B was 150.5% and 140.9% of that of model C, respectively. The stress of the screw-rod system was the highest during lateral bending (model A, 102.0 MPa), which was 108.4%, 102.4%, 110.4%, 114.2% of model B and 158.5%, 110.1%, 115.8%, 125.4% of model C in flexion, extension, lateral bending, and rotation, respectively. CONCLUSIONS: For people with osteoporosis, no matter what type of cage is used, good immediate stability can be achieved after surgery. Larger cage sizes provide better fixation without significantly increasing ROM and IDP in adjacent segments, which may contribute to the development of ASD. In addition, larger cage sizes can disperse endplate stress and reduce stress concentration, which is of positive significance in preventing cage subsidence after operation. The cage and screw rod system establish a stress conduction pathway on the spine, and a larger cage greatly enhances the stress-bearing capacity of the front column, which can better distribute the stress of the posterior spine structure and the stress borne by the posterior screw rod system, reduce the stress concentration phenomenon of the nail rod system, and avoid exceeding the yield strength of the material, resulting in the risk of future instrument failure.

Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe.

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines.

Biomechanical evaluation of different sizes of 3D printed cage in lumbar interbody fusion-a finite element analysis.

OBJECTIVE: To study the biomechanical characteristics of various tissue structures of different sizes of 3D printed Cage in lumbar interbody fusion. METHODS: A finite element model of normal spine was reconstructed and verified. Pedicle screws and Cage of different sizes were implanted in the L4/5 segment to simulate lumbar interbody fusion. The range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment were calculated and analyzed. RESULTS: The range of motion and intervertebral disc pressure of the adjacent segment of each postoperative model were larger than those of the intact model, but there was not much difference between them. The stress of cage-endplate interface was also larger than that of the intact model. However, the difference is that the stress of the endplate and the screw-rod system has a tendency to decrease with the increase of the axial area of cage. CONCLUSIONS: Cage with larger axial area in lumbar interbody fusion can reduce the stress of internal fixation system and endplate, but will not increase the range of motion and intervertebral disc pressure of adjacent segment. It has a certain effect in preventing the cage subsidence, internal fixation system failure and screw rod fracture.

Biomechanical properties of lumbar vertebral ring apophysis cage under endplate injury: a finite element analysis.

OBJECTIVE: This study aimed to compare the biomechanical properties of lumbar interbody fusion involving two types of cages. The study evaluated the effectiveness of the cage spanning the ring apophysis, regardless of the endplate's integrity. METHODS: A finite element model of the normal spine was established and validated in this study. The validated model was then utilized to simulate Lateral Lumbar Interbody Fusion (LLIF) with posterior pedicle screw fixation without posterior osteotomy. Two models of interbody fusion cage were placed at the L4/5 level, and the destruction of the bony endplate caused by curetting the cartilaginous endplate during surgery was simulated. Four models were established, including Model 1 with an intact endplate and long cage spanning the ring apophysis, Model 2 with endplate decortication and long cage spanning the ring apophysis, Model 3 with an intact endplate and short cage, and Model 4 with endplate decortication and short cage. Analyzed were the ROM of the fixed and adjacent segments, screw rod system stress, interface stress between cage and L5 endplate, trabecular bone stress on the upper surface of L5, and intervertebral disc pressure (IDP) of adjacent segments. RESULTS: There were no significant differences in ROM and IDP between adjacent segments in each postoperative model. In the short cage model, the range of motion (ROM), contact pressure between the cage and endplate, stress in L5 cancellous bone, and stress in the screw-rod system all exhibited an increase ranging from 0.4% to 79.9%, 252.9% to 526.9%, 27.3% to 133.3%, and 11.4% to 107%, respectively. This trend was further amplified when the endplate was damaged, resulting in a maximum increase of 88.6%, 676.1%, 516.6%, and 109.3%, respectively. Regardless of the integrity of the endplate, the long cage provided greater support strength compared to the short cage. CONCLUSIONS: Caution should be exercised during endplate preparation and cage placement to maintain the endplate's integrity. Based on preoperative X-ray evaluation, the selection of a cage that exceeds the width of the pedicle by at least 5 mm (ensuring complete coverage of the vertebral ring) has demonstrated remarkable biomechanical performance in lateral lumbar interbody fusion procedures. By opting for such a cage, we expect a reduced occurrence of complications, including cage subsidence, internal fixation system failure, and rod fracture.

Planning a water-constrained ecological restoration pattern to enhance sustainable landscape management in drylands.

Ecological restoration is an important approach to improving landscape sustainability. However, ecological restoration in drylands is strongly limited by water resources. Therefore, a technical route for ecological restoration in drylands that creates sustainable landscapes based on those water constraints is needed. In this study, we develop a spatially explicit framework named "Constraint-Pattern-Benefit" to plan ecological restoration patterns in Inner Mongolia, China. Based on a prediction of the ecosystem service (ES) increase under limited evapotranspiration as a water constraint, we constructed 5 landscape sustainability-related strategies with 100 ecological restoration scenarios, which considered fragmentation of restoration locations, distance to city, water consumption, and the allocation scale to determine the spatial arrangement of ecological restoration. Results show that the ES increase potential of ecological restoration under water constraints is distributed in the center of Inner Mongolia. The multi-objective scenario simultaneously achieves 59.1% water yield, 74.2% soil conservation, 57.2% sand fixation, and 52.8% carbon sequestration with 50% restored landscape. Considering the indicators of fragmentation, water consumption, and distance to city decreases the restored landscape fragmentation from 0.44 to 0.26, improves the restoration efficiency by 14.41%, and increases the beneficiary population by 35.5%, respectively. Small-scale allocation can further increase the ES realization efficiency, which is on average 4.8% higher at the city scale than at the provincial scale. Moreover, this approach focuses on the sustainable effect of the spatial arrangement on dryland landscapes at different scales, which provides methodological support for improving the sustainability of drylands.

Extraction and activity of chemical constituents from Houttuynia cordata Thunb by ultrasonic method.

Polyphenols and flavonoids are phytochemicals that have essential roles in human nutrition. In this regard, the contents of polyphenols and flavonoids in Houttuynia cordata Thunb and their antioxidant activities were evaluated in the current study. Two Houttuynia cordata materials with the same chromosome number and chemical type were used to comprehensively assess the contents of total phenols and flavonoids in different parts of H. cordata. These chemical components were extracted by the ultrasonic method. The results showed that the total phenols and antioxidant capacity of different parts of H. cordata were significantly different. The content of polyphenols in roots and stems was low, the antioxidant capacity was weak, the total phenols in flowers and leaves were high, and the antioxidant capacity was strong. Therefore, different parts of H. cordata had different pharmacological and food effects. The whole herb can be used as Chinese herbal medicine, and its young leaves and roots can be used as vegetables. Flavonoids are the main phenolic components, and total phenols are the main components of antioxidant activity. It can explain a very significant positive correlation between total phenols and flavonoids. Therefore, in the further breeding work of H. cordata, the procedure can be simplified by determining one of the above indexes to predict the varieties with high total phenolic and antioxidant activity.

Biomechanical behaviour of tension-band-reconstruction titanium plate in open-door laminoplasty: a study based on finite element analysis.

OBJECTIVE: To investigate and evaluate the biomechanical behaviour of tension-band-reconstruction (TBR) and ordinary titanium plates in open-door laminoplasty by finite element (FE) analysis. METHODS: TBR titanium plate and ordinary titanium plate were implanted into a validated finite element model of healthy adult cervical vertebrae. Among them, 5 ordinary titanium plate were used in model A, 2 TBR titanium plates and 3 ordinary titanium plates were used in model B, and 5 TBR titanium plates were used in model C. The same loading conditions was applied identically to all models. Range of motion (ROM) of the vertebral body, stress distribution of the titanium plate and intradiscal pressure (IDP) were compared in flexion, extension, lateral bending and rotation. RESULTS: The ROM of model B and C was similar in flexion and extension, and both were smaller than that of model A. The highest von Mises stress in the titanium plate appears is in model C. The IDP in C2/3 was significantly higher than that in other segments in flexion. There was no significant difference in IDP among three models in left lateral bending and left axial rotation. CONCLUSION: Application of TBR titanium plate in open-door laminoplasty can reduced ROM in flexion, extension and axial rotation of the cervical vertebrae. But the increase of stress in TBR titanium plate could lead to higher risk of adverse events such as titanium plate deformation. Moreover, compared with complete TBR titanium plate, the combination of TBR titanium plate for C3 and C7 with ordinary titanium plate for the other vertebrae largely reduce the stress of the titanium plates by ensuring stability. The proposed FE model (C2-T1) exhibits a great potential in evaluating biomechanical behaviour of TBR titanium plate for open-door laminoplasty.

Biomechanical comparison of spinal column shortening - a finite element study.

BACKGROUND: At present, research on spinal shortening is mainly focused on the safe distance of spinal shortening and the mechanism of spinal cord injury, but there is no research on the biomechanical characteristics of different shortening distances. The purpose of this study was to study the biomechanical characteristics of spine and internal fixation instruments at different shortening distances by the finite element (FE) method. METHODS: An FE model of lumbar L1-S was established and referred to the previous in vitro experiments to verify the rationality of the model by verifying the Intradiscal pressure (IDP) and the range of motion (ROM) of the motion segment. Five element models of spinal shortening were designed under the safe distance of spinal shortening, and the entire L3 vertebra and both the upper and lower intervertebral discs were resected. Model A was not shortened, while models B-E were shortened by 10%, 20%, 30% and 50% of the vertebral body, respectively. Constraining the ROM of the sacrum in all directions, a 7.5 N ·m moment and 280 N follower load were applied on the L1 vertebra to simulate the motion of the lumbar vertebrae in three planes. The ROM of the operated segments, the Von Mises stress (VMS) of the screw-rod system, the VMS of the upper endplate at the interface between the titanium cage and the L4 vertebral body, and the ROM and the IDP of the adjacent segment (L5/S) were recorded and analysed. RESULTS: All surgical models showed good stability at the operated segments (L1-5), with the greatest constraint in posterior extension (99.3-99.7%), followed by left-right bending (97.9-98.7%), and the least constraint in left-right rotation (84.9-86.3%) compared with the intact model. The VMS of the screw-rod system and the ROM and IDP of the distal adjacent segments of models A-E showed an increasing trend, in which the VMS of the screw-rod system of model E was the highest under flexion (172.5 MPa). The VMS of the endplate at the interface between the cage and L4 upper endplate of models A-E decreased gradually, and these trend were the most obvious in flexion, which were 3.03, 2.95, 2.83, 2.78, and 2.61 times that of the intact model, respectively. CONCLUSION: When performing total vertebrae resection and correcting the spinal deformity, if the corrected spine has met our needs, the distance of spinal shortening should be minimized to prevent spinal cord injury, fracture of internal fixations and adjacent segment disease (ASD).

Adsorption behavior of Ni(II) onto activated carbons from hide waste and high-pressure steaming hide waste.

This work reports the preparation and adsorption of Ni(II) via activated carbons which produced from hide waste (HWAC) and high-pressure steaming hide waste (HWSAC) with potassium silicate as the activating agent. The best preparation condition for HWAC and HWSAC was the activation temperature of 700 °C using an impregnation ratio of 2:1. Both of them were characterized by N2 adsorption/desorption isotherms, SEM and FT-IR spectra. The surface area of HWAC and HWSAC was 1804.37 and 1361.26 m2/g, respectively. Despite the surface area of HWAC being larger than that of HWSAC, but the adsorption capacity of Ni(II) for HWAC was lower than that for HWSAC. Furthermore, the adsorption capacity of Ni(II) for both HWAC and HWSAC showed pH-dependent behavior and increased with the increase in pH value, which can be attributed to the functional groups of HWAC and HWSAC materials through the electrostatic attraction. The adsorption data for HWAC and HWSAC were fitted with four isotherm models (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich) and four kinetic models (pseudo-first order model, pseudo-second order model, intra-particle diffusion and Elovich equation), indicating that Langmuir isotherm and Pseudo-second order model fitted well with high coefficient of determination (R2 > 0.99) for both the two adsorbents. The positive enthalpy of adsorption (ΔH) and free energy of adsorption (ΔG) indicate a spontaneous and endothermic nature of the process. These results demonstrated that activated carbon can be prepared from hide waste which could remove heavy metal such as Ni(II) effectively.

Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4.

Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression.

Distinct allelic patterns of nanog expression impart embryonic stem cell population heterogeneity.

Nanog is a principal pluripotency regulator exhibiting a disperse distribution within stem cell populations in vivo and in vitro. Increasing evidence points to a functional role of Nanog heterogeneity on stem cell fate decisions. Allelic control of Nanog gene expression was reported recently in mouse embryonic stem cells. To better understand how this mode of regulation influences the observed heterogeneity of NANOG in stem cell populations, we assembled a multiscale stochastic population balance equation framework. In addition to allelic control, gene expression noise and random partitioning at cell division were considered. As a result of allelic Nanog expression, the distribution of Nanog exhibited three distinct states but when combined with transcriptional noise the profile became bimodal. Regardless of their allelic expression pattern, initially uniform populations of stem cells gave rise to the same Nanog heterogeneity within ten cell cycles. Depletion of NANOG content in cells switching off both gene alleles was slower than the accumulation of intracellular NANOG after cells turned on at least one of their Nanog gene copies pointing to Nanog state-dependent dynamics. Allelic transcription of Nanog also raises issues regarding the use of stem cell lines with reporter genes knocked in a single allelic locus. Indeed, significant divergence was observed in the reporter and native protein profiles depending on the difference in their half-lives and insertion of the reporter gene in one or both alleles. In stem cell populations with restricted Nanog expression, allelic regulation facilitates the maintenance of fractions of self-renewing cells with sufficient Nanog content to prevent aberrant loss of pluripotency. Our findings underline the role of allelic control of Nanog expression as a prime determinant of stem cell population heterogeneity and warrant further investigation in the contexts of stem cell specification and cell reprogramming.

The environmental impact assessment of China's ecological migration from a social-ecological perspective.

When accounting for the social-ecological impact of an ecological restoration program, both objective environmental contexts and people's subjective perceptions are required. While this kind of environmental impact assessment lacks a comprehensive perspective. We use the difference-in-differences model to evaluate the effect of the greenness of the landscape after ecological migration in the Qilian Mountains in China; and analysis of variance and fixed effects models are used to evaluate the effects of such ecological restoration programs on local people's perceptions. The results show that the ecological migration program in the Qilian Mountains has been successful at not only significantly improving remotely sensed greenness at the landscape scale, but also at enhancing immigrants' environmental perceptions. These findings demonstrate the environmental impacts of ecological migration from a social-ecological perspective, and can provide methodological implications for landscape planning to support a better understanding of ecological restoration programs in the drylands.

A bibliometric and visualization analysis of global research status and frontiers on autophagy in cardiomyopathies from 2004 to 2023.

BACKGROUND: Autophagy is intimately associated with the development of cardiomyopathy, and has received widespread attention in recent years. However, no relevant bibliometric analysis is reported at present. In order to summarize the research status of autophagy in cardiomyopathy and provide direction for future research, we conducted a comprehensive, detailed, and multidimensional bibliometric analysis of the literature published in this field from 2004 to 2023. METHODS: All literatures related autophagy in cardiomyopathy from 2004 to 2023 were collected from the Web of Science Core Collection (WOSCC), and annual papers, global publication trends and proportion charts were analyzed and plotted using Graphpad price v8.0.2. In addition, CtieSpace (6.2.4R (64 bit) Advanced Edition) and VOSviewer (1.6.18 Edition) were used to analyze and visualize these data. RESULTS: 2279 papers about autophagy in cardiomyopathy were accessed in the WoSCC over the last 20 years, comprising literatures from 70 countries and regions, 2208 institutions, and 10,810 authors. China contributes 56.32% of the total publications, substantially surpassing other countries, while the U.S. is ranked first in frequency of citations. Among the top 10 authors, 6 are from China and 4 are from the United States. Air Force Military Medical University was the institution with the highest number of publications; while journal of molecular and cellular cardiology (62 articles, 2.71% of the total) was the journal with the highest number of papers published in the field. Clustering of co-cited references and temporal clustering analysis showed that ferroptosis, hydrogen sulfide mitophagy, lipid peroxidation, oxidative stress, and SIRT-1 are hot topics and trends in the field. The principal keywords are oxidative stress, heart and heart-failure. CONCLUSION: The research on autophagy in cardiomyopathy is in the developmental stage. This represents the first bibliometric analysis of autophagy in cardiomyopathy , revealing the current research hotspots and future research directions in this field.

Preparation, characterization, and application of gallic acid-mediated photodynamic chitosan-nanocellulose-based films.

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e-12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products.

Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial.

OBJECTIVES: Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy. MATERIALS AND METHODS: CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression. Patients were randomized to canakinumab plus docetaxel or placebo plus docetaxel. RESULTS: A total of 237 patients were randomly allocated: 120 (51 %) to canakinumab and 117 (49 %) to placebo, stratified by histology and prior lines of therapy. Three patients in the placebo arm did not receive study treatment. The trial did not meet its primary endpoint of overall survival: median 10.6 months (95 % confidence interval [CI], 8.2-12.4) for the canakinumab arm and 11.3 months (95 % CI, 8.5-13.8) for the placebo arm (hazard ratio, 1.06 [95 % CI, 0.76-1.48]; one-sided P-value = 0.633). AEs (any grade) were reported in 95 % of patients in the canakinumab group and in 98 % of patients in the placebo group. Grade 3-4 AEs were experienced by 62 % and 64 % of patients in the canakinumab and placebo groups, respectively, and grade 5 AEs were experienced by 8 % and 5 %. Prespecified, post-hoc subgroup analyses showed that patients with undetected circulating tumor DNA (ctDNA) and/or lower levels (< 10 mg/L) of C-reactive protein (CRP) achieved longer progression-free and overall survival than those with detected ctDNA or higher (≥ 10 mg/L) CRP levels. There was no association with treatment arm. CONCLUSION: Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy. CLINICAL REGISTRATION: NCT03626545.

Migraine and risk of rheumatoid arthritis: A systematic review and meta-analysis of observational studies.

Background: Exposure to Migraine may be one of the risk factors for the onset of rheumatoid arthritis (RA), while the relationship between the two is debatable. In this study, the connection between migraine and the risk of RA was investigated using a systematic review and meta-analysis of the pertinent literature. Methods: Up to July 2022, the PubMed, EMBASE, Web of Science (WOS), and scopus databases were employed to search for observational studies on the risk of RA in migraineurs. The effect sizes were pooled using a random-effects model or a fixed-effects model. Results: Out of 2345 records, 5 studies (3 case and control studies and 2 cohort studies) were identified and included in the meta-analysis. According to a pooled analysis, migraine sufferers had a higher chance of developing RA (pooled adjusted effect estimate: 1.94, 95% confidence interval: 1.74-2.17; p < 0.01). Conclusions: Migraine can be legitimately regarded as a risk factor for RA since this study demonstrated a relationship between migraine and RA. This conclusion should be treated with caution due to low power and precision. Rigorous design and larger sample sizes of studies are needed to verify the findings.

A tetrahedron from homooxacalix[3]arene, the fifth Platonic polyhedron from calixarenes and uranyl.

A self-assembled tetrahedral cage results from two C 3-symmetry building blocks, namely, homooxacalix[3]arene tricarboxylate and uranyl cation, as demonstrated by X-ray crystallography. In the cage, four metals coordinate at the lower rim with the phenolic and ether oxygen atoms to shape the macrocycle with appropriate dihedral angles for tetrahedron formation, whereas four additional uranyl cations further coordinate at the upper-rim carboxylates to finalize the assembly. Counterions dictate the filling and porosity of the aggregates, whereas potassium induces highly porous structures, and tetrabutylammonium yields compact, densely packed frameworks. The tetrahedron metallo-cage complements our previous report (Pasquale et al., Nat. Commun., 2012, 3, 785) on uranyl-organic frameworks (UOFs) from calix[4]arene and calix[5]arene carboxylates (octahedral/cubic and icosahedral/dodecahedral giant cages, respectively) and completes the assembly of all five Platonic solids from just two chemical components.