GAN-based metal artifacts region inpainting in brain MRI imaging with reflective registration.

BACKGROUND AND OBJECTIVE: Metallic magnetic resonance imaging (MRI) implants can introduce magnetic field distortions, resulting in image distortion, such as bulk shifts and signal-loss artifacts. Metal Artifacts Region Inpainting Network (MARINet), using the symmetry of brain MRI images, has been developed to generate normal MRI images in the image domain and improve image quality. METHODS: T1-weighted MRI images containing or located near the teeth of 100 patients were collected. A total of 9000 slices were obtained after data augmentation. Then, MARINet based on U-Net with a dual-path encoder was employed to inpaint the artifacts in MRI images. The input of MARINet contains the original image and the flipped registered image, with partial convolution used concurrently. Subsequently, we compared PConv with partial convolution, and GConv with gated convolution, SDEdit using a diffusion model for inpainting the artifact region of MRI images. The mean absolute error (MAE) and peak signal-to-noise ratio (PSNR) for the mask were used to compare the results of these methods. In addition, the artifact masks of clinical MRI images were inpainted by physicians. RESULTS: MARINet could directly and effectively inpaint the incomplete MRI images generated by masks in the image domain. For the test results of PConv, GConv, SDEdit, and MARINet, the masked MAEs were 0.1938, 0.1904, 0.1876, and 0.1834, respectively, and the masked PSNRs were 17.39, 17.40, 17.49, and 17.60 dB, respectively. The visualization results also suggest that the network can recover the tissue texture, alveolar shape, and tooth contour. Additionally, for clinical artifact MRI images, MARINet completed the artifact region inpainting task more effectively when compared with other models. CONCLUSIONS: By leveraging the quasi-symmetry of brain MRI images, MARINet can directly and effectively inpaint the metal artifacts in MRI images in the image domain, restoring the tooth contour and detail, thereby enhancing the image quality.

Nucleic Acid Detection through RNA-Guided Protease Activity in Type III-E CRISPR-Cas Systems.

RNA-guided protease activity was recently discovered in the type III-E CRISPR-Cas systems (Craspase), providing a novel platform for engineering a protein probe instead of the commonly used nucleic acid probe in the nucleic acid detection assays. Here, by adapting a fluorescence readout technique using the affinity- and fluorescent protein dual-tagged Csx30 protein substrate, we established an assay monitoring Csx30 cleavage by target ssRNA-activated Craspase. Four Craspase-based nucleic acid detection systems for genes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), norovirus, and the influenza virus (IFV) were reconstituted with demonstrated specificity. The assay could reliably detect target ssRNAs with concentrations down to 25 pM, which could be further improved by approximately 15,000-fold (~ 2 fM) through incorporating the recombinase polymerase isothermal preamplification step. Importantly, the species-specific substrate cleavage specificity of Craspase enabled multiplexed diagnosis, as demonstrated by the reconstituted composite systems for simultaneous detection of two genes from the same virus (SARS-CoV-2, spike and nsp12) or two types of viruses (SARS-CoV-2 and IFV). The assay could be further expanded by diversifying the fluorescent tags in the substrate and including Craspase systems of various species, potentially providing an easily adaptable platform for clinical diagnosis.

Ultrafast Study of Excited State Dynamics of Amino Metal Halide Molecular Clusters.

The excited state dynamics of ligand-passivated PbBr2 molecular clusters (MCs) in solution have been investigated for the first time using femtosecond transient absorption spectroscopy. The results uncover a transient bleach (TB) feature peaked around 404 nm, matching the ground state electronic absorption band peaked at 404 nm. The TB recovery signal can be fitted with a triple exponential with fast (10 ps), medium (350 ps), and long (1.8 ns) time constants. The medium and long time constants are very similar to those observed in the time-resolved photoluminescence (TRPL) decay monitored at 412 nm. The TB fast component is attributed to vibrational relaxation in the excited electronic state while the medium component with dominant amplitude is attributed to recombination between the relaxed electron and hole. The small amplitude slow component is assigned to electrons in a relatively long-lived excited electronic state, e.g., triplet state, or shallow trap state due to defects. This study provides new insights into the excited state dynamics of metal halide MCs.

[Effects of Combined Stress of Polyethylene and Sulfamethazine on Seed Germination, Seedling Growth, and Physiological Characteristics of Soybean].

The combined pollution of antibiotics adsorption by microplastics has become inevitable in soil ecosystems; moreover, the plant biological effects under combined stress remain unclear. This study used soybean variety Jindou 21 as the material and conducted seed germination test and soil-potted seedling experiment to study the effects of different single and combined treatments of polyethylene (PE) and sulfamethazine (SMZ) on seed germination, seedling growth, photosynthetic parameters, chlorophyll fluorescence parameters, and nitrogen metabolism. The results showed that single PE treatment at low levels promoted soybean seed germination and seedling growth physiology; however, inhibited them at a high level. A lower-level PE treatment[10 mg·L-1 (or mg·kg-1)] could promote soybean seed germination, seedling growth, photosynthesis, and nitrogen metabolism, whereas a higher level PE treatment[100 mg·L-1 and 200 mg·L-1 (or mg·kg-1)] had significant inhibition. The single SMZ treatment had different degrees of inhibition on soybean seed germination and seedling growth physiology, and the inhibition degree increased with the increase in SMZ treatment level. Under the different levels of combined treatments of PE and SMZ, adding the lower level PE treatment could alleviate the inhibition of the single SMZ treatment on soybean, with 10 mg·L-1(or mg·kg-1) PE+1 mg·L-1(or mg·kg-1) SMZ treatment having the best comprehensive mitigation effect, which could increase soybean seed germination potential, germination rate, germination index, vigor index, plant height, root length, shoot and root fresh weight, Pn, Gs, Tr, chlorophyll contents, Fv/Fm, ΦPSⅡ, ETR, qP, and key enzyme activities for nitrogen metabolism such as NR and decrease the average germination time, Ci, NPQ, and NO3--N and NH4+-N contents compared with those in the single SMZ treatment. Adding the higher level PE treatment enhanced the inhibition of SMZ on soybean, and the inhibition degree increased with the increase in SMZ treatment level, in which 200 mg·L-1(or mg·kg-1) PE+50 mg·L-1(or mg·kg-1) SMZ treatment yielded the greatest inhibition. In summary, the lower level PE treatment could alleviate the inhibition of SMZ on soybean seeds and seedlings to a certain extent; however, the higher level PE treatment could produce a synergistic effect with SMZ, thus aggravating the toxic effect of the single stress treatment.

Design, synthesis of (±)-millpuline A and biological evaluation for the lung cell protective effects through SRC.

In this paper, a visible-light-induced intermolecular [2+2] photocycloaddition reaction based on flavonoids was constructed to address the problems of low yield, poor physicochemical properties, and lack of target definition in total synthesis of (±)-millpuline A whose bioactivity remains unknown. As a result, 20 derivatives (B1-B20) were synthesized for bioactivity evaluation. Consequently, lung cell protective effects of (±)-millpuline A and B13a were revealed for the first time and the crucial role of stereoconfiguration of the cyclobutane moiety in their protective effects against NNK in normal lung cells was demonstrated. Moreover, through target prediction and experimental verification in MLE-12 cells, SRC was determined to be the target of (±)-millpuline A regarding its protective effect in NNK-induced lung cell injury. Results from RT-Q-PCR and HTRF experiments verified that (±)-millpuline A could repress SRC activity through a transcriptional mechanism but not acting as an inhibitor to directly bind to and thereby inhibit SRC protein. The results in this paper are informative for the further development of visible light-catalyzed cycloaddition of flavon-oids and lay a scientific foundation for understanding the bioactivity and underlying mechanism of (±)-millpuline A and other structurally similar natural skeletons.

Efficient FMT reconstruction based on L1-αL2 regularization via half-quadratic splitting and a two-probe separation light source strategy.

Fluorescence molecular tomography (FMT) can achieve noninvasive, high-contrast, high-sensitivity three-dimensional imaging in vivo by relying on a variety of fluorescent molecular probes, and has excellent clinical transformation prospects in the detection of tumors in vivo. However, the limited surface fluorescence makes the FMT reconstruction have some ill-posedness, and it is difficult to obtain the ideal reconstruction effect. In this paper, two different emission fluorescent probes and L 1-L 2 regularization are combined to improve the temporal and spatial resolution of FMT visual reconstruction by introducing the weighting factor α and a half-quadratic splitting alternating optimization (HQSAO) iterative algorithm. By introducing an auxiliary variable, the HQSAO method breaks the sparse FMT reconstruction task into two subproblems that can be solved in turn: simple reconstruction and image denoising. The weight factor α (α>1) can increase the weight of nonconvex terms to further promote the sparsity of the algorithm. Importantly, this paper combines two different dominant fluorescent probes to achieve high-quality reconstruction of dual light sources. The performance of the proposed reconstruction strategy was evaluated by digital mouse and nude mouse single/dual light source models. The simulation results show that the HQSAO iterative algorithm can achieve more excellent positioning accuracy and morphology distribution in a shorter time. In vivo experiments also further prove that the HQSAO algorithm has advantages in light source information preservation and artifact suppression. In particular, the introduction of two main emission fluorescent probes makes it easy to separate and reconstruct the dual light sources. When it comes to localization and three-dimensional morphology, the results of the reconstruction are much better than those using a fluorescent probe, which further facilitates the clinical transformation of FMT.

A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis.

BACKGROUND: Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism. METHODS: We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments. RESULTS: The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 (ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and be significantly associated with severe survival outcomes. CONCLUSION: The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.

Melatonin enhances the developmental potential of immature oocytes from older reproductive-aged women by improving mitochondrial function.

Aims: To evaluate whether melatonin (MT) supplementation during in vitro maturation (IVM) of human oocytes can reverse the age-related decline in oocyte quality. Main methods: We enrolled 172 patients aged ≥35 years (older reproductive-aged women) and 83 patients aged <35 years (young women) who underwent in vitro fertilization between 2019 and 2022. We conducted IVM with and without 10 µM MT in immature oocytes of different ages. Oocyte fertilization and embryo development were observed using a stereomicroscope. We assessed the immunofluorescence intensity of mitochondrial function, measured the copy number of mitochondrial DNA (mtDNA), and examined the spindle and chromosome composition in in vitro mature stage II (IVM-MII) oocytes using immunofluorescence and second-generation sequencing. Key findings: MT supplementation significantly improved the redox level in the IVM medium and IVM-MII oocytes in older reproductive-aged women. It also significantly increased the proportion of circular mtDNA and the adenosine triphosphate content in IVM-MII oocytes. In addition, the IVM-MII oocytes obtained with MT supplementation showed a significant improvement in the normal composition of the spindle and chromosomes. Thus, the aged immature oocytes also showed significantly improved maturation and blastocyst formation rates owing to the role of MT. Significance: Supplementation with 10 µM MT in the IVM medium reverses the age-related decline in oocyte quality. Our findings provide a viable solution for enhancing fertility in older reproductive-aged women.

A new polymodal gating model of the proton-activated chloride channel.

The proton-activated chloride (PAC) channel plays critical roles in ischemic neuron death, but its activation mechanisms remain elusive. Here, we investigated the gating of PAC channels using its novel bifunctional modulator C77304. C77304 acted as a weak activator of the PAC channel, causing moderate activation by acting on its proton gating. However, at higher concentrations, C77304 acted as a weak inhibitor, suppressing channel activity. This dual function was achieved by interacting with 2 modulatory sites of the channel, each with different affinities and dependencies on the channel's state. Moreover, we discovered a protonation-independent voltage activation of the PAC channel that appears to operate through an ion-flux gating mechanism. Through scanning-mutagenesis and molecular dynamics simulation, we confirmed that E181, E257, and E261 in the human PAC channel serve as primary proton sensors, as their alanine mutations eliminated the channel's proton gating while sparing the voltage-dependent gating. This proton-sensing mechanism was conserved among orthologous PAC channels from different species. Collectively, our data unveils the polymodal gating and proton-sensing mechanisms in the PAC channel that may inspire potential drug development.

Application of Deep Learning in Cancer Prognosis Prediction Model.

As an important branch of artificial intelligence and machine learning, deep learning (DL) has been widely used in various aspects of cancer auxiliary diagnosis, among which cancer prognosis is the most important part. High-accuracy cancer prognosis is beneficial to the clinical management of patients with cancer. Compared with other methods, DL models can significantly improve the accuracy of prediction. Therefore, this article is a systematic review of the latest research on DL in cancer prognosis prediction. First, the data type, construction process, and performance evaluation index of the DL model are introduced in detail. Then, the current mainstream baseline DL cancer prognosis prediction models, namely, deep neural networks, convolutional neural networks, deep belief networks, deep residual networks, and vision transformers, including network architectures, the latest application in cancer prognosis, and their respective characteristics, are discussed. Next, some key factors that affect the predictive performance of the model and common performance enhancement techniques are listed. Finally, the limitations of the DL cancer prognosis prediction model in clinical practice are summarized, and the future research direction is prospected. This article could provide relevant researchers with a comprehensive understanding of DL cancer prognostic models and is expected to promote the research progress of cancer prognosis prediction.

Domino Reactions Enabling Sulfur-Mediated Gradient Interphases for High-Energy Lithium Batteries.

Silicon (Si)-based anodes are currently considered a feasible solution to improve the energy density of lithium-ion batteries owing to their sufficient specific capacity and natural abundance. However, Si-based anodes exhibit low electric conductivities and large volume changes during cycling, which could easily trigger continuous breakdown/reparation of the as-formed solid-electrolyte-interphase (SEI) layer, seriously hampering their practical application in current battery technology. To control the chemoelectrochemical instability of the conventional SEI layer, we herein propose the introduction of elemental sulfur into nonaqueous electrolytes, aiming to build a sulfur-mediated gradient interphase (SMGI) layer on Si-based anodes. The SMGI layer is generated through the domino reactions (i.e., electrochemical cascade reactions) involving the electrochemical reductions of elemental sulfur followed by nucleophilic substitutions of fluoroethylene carbonate, which endows the corresponding SEI layer with strong elasticity and chemomechanical stability and enables rapid transportation of Li+ ions. Consequently, the prototype Si||LiNi0.8Co0.1Mn0.1O2 cells attain a high-energy density of 622.2 W h kg-1 and a capacity retention of 88.8% after 100 cycles. Unlike previous attempts based on sophisticated chemical modifications of electrolyte components, this study opens a new avenue in interphase design for long-lived and high-energy rechargeable batteries.

A nomogram for predicting post-operative hydrocephalus in children with medulloblastoma.

Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.

A dual pH- and temperature-responsive hydrogel produced in situ crosslinking of cyclodextrin-cellulose for wound healing.

Cellulose hydrogels have gained attention in the field of wound healing due to their biodegradability, biocompatibility, and the capacity to sustain a humid environment that promotes healing. Conventional cellulose hydrogels were usually lacked responsiveness to changing wound conditions, and limited capacity for controlled release of active substances. The composite hydrogels with Berberine (BBR) loading were prepared from bamboo parenchymal cellulose and in situ crosslinking carboxylated-ß-cyclodextrin (BPCH-B) via dissolution. The inclusion of BBR enhanced the antibacterial properties of cellulose hydrogel while maintaining biocompatibility and drug delivery capabilities. The dual-responsive dressing was demonstrated to modulate drug release kinetics in accordance with the pH and temperature conditions prevailing within the wound site. Specifically, study exhibited a significant increase in drug release (over 70 %) under alkaline pH (7.6) and temperature (40 °C) conditions. Full-thickness wound healing experiments indicated that BPCH-B had better healing ability, and the wound healing area of BPCH-B treated was 80 % within 12 days, while the control group was only 50 %. This strategy for generating functional wound healing can be further control release of drug compounds for treatment of wounds, enabling development of practical wound care materials.

Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of Cyr61 m6A.

BACKGROUND: Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. OBJECTIVES: This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. METHODS: Dams were exposed to 0.15, 1.5, and 15mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2µM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. N6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation-quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case-control study verified the findings. RESULTS: Sizes of fetuses (exposed to 1.5 and 15mg/L NaAsO2) and placentas (exposed to 15mg/L NaAsO2) were lower in As-exposed mice. More glycogen+ trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the 15mg/L NaAsO2-exposed mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 m6A. Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 m6A was affected. Depletion of intracellular SAM, a cofactor for m6A methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 m6A down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. DISCUSSION: Using in vitro and in vivo models, we found that intracellular SAM depletion-mediated Cyr61 m6A down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. https://doi.org/10.1289/EHP12207.

Micropollutants but high risks: Human multiple stressors increase risks of freshwater ecosystems at the megacity-scale.

Micropollutants in water environments have attracted widespread attention, but how human and natural stressors influence the risks of micropollutants has not been comprehensively revealed. A megacity-scale study of the ecological risks of micropollutants in the surface water of Beijing, China is presented to illustrate the magnitudes of the influences of multiple anthropogenic and natural stressors. A total of 133 micropollutants representing typical land use patterns in Beijing, were quantified with the mean concentration range of ND (not detected) to 272 ng·L-1. The micropollutant concentrations in the south were obviously higher than those detected in the northern areas, and neonicotinoid pesticides showed the highest mean concentration of 311 ng·L-1. The chronic and acute risks of micropollutants to algae, invertebrates, and fishes were determined, and herbicides, organophosphorus esters, and insecticides account for the primary risks to algae, invertebrates, and fishes, respectively. The cropland and impervious cover cause the differences in the pollution and risks of micropollutants. The land use in riparian zones greater than 2 km shows a great influence on the chronic chemical risks (CCRs) for the three groups of species, indicating that too local scale does not explain the local pollution status. Climate conditions and human land use are important drivers explaining the CCRs to which various trophic levels of species are exposed. Results demonstrate that multiple categories of micropollutants pose adverse risks to freshwater in the megacity of Beijing, while climate conditions, pollution discharge, and human land use induce the chemical risk of micropollutants to aquatic organisms, and the land use in different riparian zones show different effects on the risks.

Synergistic antitumor efficacy of gemcitabine and cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via Sp1-SAT1-polyamine metabolism pathway.

PURPOSE: The combination of cisplatin and gemcitabine-based chemotherapy has been recommended as a preferred regimen for pancreatic ductal adenocarcinoma (PDAC) patients with germline-based mutations. However, the underlying mechanism remains poorly elucidated. Therefore, our study aimed to explore the mechanistic basis of the cell-killing activity of gemcitabine plus cisplatin and identify potential therapeutic targets. METHODS: First, we explored the synergistic cytotoxic effects of gemcitabine and cisplatin on PDAC through in vitro and in vivo experiments. Then, we investigated ferroptosis-related biomarkers, to assess the impact of the combination therapy on ferroptosis. Using bioinformatics methods, we identified SAT1 as a potential key mediator of ferroptosis induced by gemcitabine and cisplatin. We tested the polyamine levels in PDAC cells by LC-MS after overexpressed or knocked down SAT1, and explored the role of polyamines in ferroptosis using exogenous supplementation. Finally, we explored the regulatory effect of Sp1 on SAT1 through ChIP-qPCR and dual-luciferase reporter assay. RESULTS: Gemcitabine plus cisplatin enhanced cell death and induced ferroptosis in PDAC. This combination upregulated SAT1 transcription by inhibiting Sp1. SAT1 activation promoted the catabolism of spermine and spermidine, leading to iron accumulation and lipid peroxide generation, ultimately resulting in ferroptosis. CONCLUSIONS: In summary, our findings suggested the gemcitabine and cisplatin combination therapy induced ferroptosis in a GSH-independent manner in PDAC. The combined treatment inhibited Sp1 and upregulated SAT1 transcription, leading to the breakdown of spermine and spermidine. Therefore, targeting SAT1-induced polyamine metabolism may represent a promising therapeutic strategy for PDAC.

Dosage compensation of Z sex chromosome genes in avian fibroblast cells.

In birds, sex is genetically determined; however, the molecular mechanism is not well-understood. The avian Z sex chromosome (chrZ) lacks whole chromosome inactivation, in contrast to the mammalian chrX. To investigate chrZ dosage compensation and its role in sex specification, we use a highly quantitative method and analyze transcriptional activities of male and female fibroblast cells from seven bird species. Our data indicate that three fourths of chrZ genes are strictly compensated across Aves, similar to mammalian chrX. We also present a complete list of non-compensated chrZ genes and identify Ribosomal Protein S6 (RPS6) as a conserved sex-dimorphic gene in birds.

Circadian gene ARNTL initiates circGUCY1A2 transcription to suppress non-small cell lung cancer progression via miR-200c-3p/PTEN signaling.

BACKGROUND: As a subclass of endogenous stable noncoding RNAs, circular RNAs are beginning to be appreciated for their potential as tumor therapeutics. However, the functions and mechanisms by which circRNAs exert protective functions in non-small cell lung cancer (NSCLC) remain largely elusive. METHODS: The prognostic role of circGUCY1A2 was explored in lung adenocarcinoma specimens. The overexpressed and knockdown plasmids were used to evaluate the effect of circGUCY1A2 on NSCLC cell proliferation and apoptosis efficacy. Luciferase reporter system is used to prove that circGUCY1A2 could bind to miRNA. Chip-PCR was used to prove that circGUCY1A2 could be initiated by transcription factors ARNTL. Subcutaneous tumorigenicity grafts models were established to validate findings in vivo. RESULTS: The expression of circGUCY1A2 were significantly reduced (P < 0.001) and negatively correlated with tumor size (P < 0.05) in non-small cell lung cancer (NSCLC). CircGUCY1A2 upregulation promoted apoptosis and inhibits cell proliferation and growth of subcutaneous tumorigenicity grafts in nude mice (P < 0.01). In addition, intra-tumor injection of pLCDH-circGUCY1A2 inhibited tumor growth in patient-derived NSCLC xenograft models (PDX). Mechanism studies showed that circGUCY1A2 could act as a sponge to competitively bind miR-200c-3p, promote PTEN expression, and thereby inhibit PI3K/AKT pathway. In addition, we found that the circadian gene ARNTL, which was reduced in NSCLC and prolonged the overall survival of patients, could bind to the promoter of circGUCY1A2, thereby increasing its expression. CONCLUSIONS: This study is an original demonstration that ARNTL can inhibit the development of lung adenocarcinoma through the circGUCY1A2/miR-200c-3p/PTEN axis, and this finding provides potential targets and therapeutic approaches for the treatment of lung adenocarcinoma.

Contralateral seventh cervical nerve transfer for central spastic arm paralysis: a systematic review and meta-analysis.

Objectives: The specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis. Materials and methods: PRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity. Results: The meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19-3.84, p < 0.00001) and had superior improvement in range of motion compared to the rehabilitation group (SMD 2.88, 95% CI = 2.47-3.29, p < 0.00001). In addition, the spasticity in the paralyzed upper extremity significantly improved in patients with CC7 transfer (SMD -1.42, 95% CI = -1.60 to -1.25, p < 0.00001). Conclusion: Our findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function.

Changes of health-related quality of life after initiating basal insulin treatment among people with type 2 diabetes.

To assess the association between insulin regimens and health-related quality of life (HRQoL) after the introduction of basal insulin (BI) among people with type 2 diabetes in real-world clinical settings. 16,339 registered people with diabetes who had inadequate glycaemic control by oral agents initiated BI (either single BI or Basal-bolus) and completed a 6-month follow-up from 209 hospitals were included in the analyses. At the end of the follow-up, the switches of insulin regimens, change of HRQoL (EQ-5D-3L) and their associations were assessed. Initial insulin regimens of single BI and of basal-bolus (BI included Glargine, Detemir, and Neutral Protamine Hagedorn) accounted for 75.6% and 24.4%, respectively. At 6 months, regimens used were BI alone (65.2%), basal-bolus (10.4%), and premixed (6.4%), whereas 17.9% stopped all insulin therapy. The visual analogue scale score increased by 5.46 (P < .001), and the index value increased slightly by 0.02 (P < .001). Univariate analysis showed that people with diabetes taking basal-bolus regimen had the greatest improvement on HRQoL in all dimensions, especially in the reduction of the percentage of Pain/Discomfort (by 10.03%) and Anxiety/Depression (by 11.21%). In multivariable analysis, single BI or premixed insulin at 6 months was associated with more improvement of visual analogue scale score compared with stopping all insulin. Improved HRQoL was observed after initiating BI in people with type 2 diabetes . If the same achievement on HbA1c control can be guaranteed, single BI is preferred to other regimens from the viewpoint of HRQoL. Basal-bolus has the most significant potential to increase HRQoL, however, the people with diabetes characteristics differ from those initiating BI alone. Further longitudinal cohort study with a longer study period might be necessary to evaluate the certain effect.