Narrowing the semantic gaps in U-Net with learnable skip connections: The case of medical image segmentation.

Current state-of-the-art medical image segmentation techniques predominantly employ the encoder-decoder architecture. Despite its widespread use, this U-shaped framework exhibits limitations in effectively capturing multi-scale features through simple skip connections. In this study, we made a thorough analysis to investigate the potential weaknesses of connections across various segmentation tasks, and suggest two key aspects of potential semantic gaps crucial to be considered: the semantic gap among multi-scale features in different encoding stages and the semantic gap between the encoder and the decoder. To bridge these semantic gaps, we introduce a novel segmentation framework, which incorporates a Dual Attention Transformer module for capturing channel-wise and spatial-wise relationships, and a Decoder-guided Recalibration Attention module for fusing DAT tokens and decoder features. These modules establish a principle of learnable connection that resolves the semantic gaps, leading to a high-performance segmentation model for medical images. Furthermore, it provides a new paradigm for effectively incorporating the attention mechanism into the traditional convolution-based architecture. Comprehensive experimental results demonstrate that our model achieves consistent, significant gains and outperforms state-of-the-art methods with relatively fewer parameters. This study contributes to the advancement of medical image segmentation by offering a more effective and efficient framework for addressing the limitations of current encoder-decoder architectures. Code: https://github.com/McGregorWwww/UDTransNet.

High flow nasal cannula oxygen therapy versus non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: a randomized controlled non-inferiority trial.

BACKGROUND: Although cumulative studies have demonstrated a beneficial effect of high-flow nasal cannula oxygen (HFNC) in acute hypercapnic respiratory failure, randomized trials to compare HFNC with non-invasive ventilation (NIV) as initial treatment in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients with acute-moderate hypercapnic respiratory failure are limited. The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients. METHODS: Patients diagnosed with AECOPD with a baseline arterial blood gas pH between 7.25 and 7.35 and PaCO2 ≥ 50 mmHg admitted to two intensive care units (ICUs) at a large tertiary academic teaching hospital between March 2018 and December 2022 were randomly assigned to HFNC or NIV. The primary endpoint was the rate of treatment failure, defined as endotracheal intubation or a switch to the other study treatment modality. Secondary endpoints were rates of intubation or treatment change, blood gas values, vital signs at one, 12, and 48 h, 28-day mortality, as well as ICU and hospital lengths of stay. RESULTS: 225 total patients (113 in the HFNC group and 112 in the NIV group) were included in the intention-to-treat analysis. The failure rate of the HFNC group was 25.7%, while the NIV group was 14.3%. The failure rate risk difference between the two groups was 11.38% (95% CI 0.25-21.20, P = 0.033), which was higher than the non-inferiority cut-off of 9%. In the per-protocol analysis, treatment failure occurred in 28 of 110 patients (25.5%) in the HFNC group and 15 of 109 patients (13.8%) in the NIV group (risk difference, 11.69%; 95% CI 0.48-22.60). The intubation rate in the HFNC group was higher than in the NIV group (14.2% vs 5.4%, P = 0.026). The treatment switch rate, ICU and hospital length of stay or 28-day mortality in the HFNC group were not statistically different from the NIV group (all P > 0.05). CONCLUSION: HFNC was not shown to be non-inferior to NIV and resulted in a higher incidence of treatment failure than NIV when used as the initial respiratory support for AECOPD patients with acute-moderate hypercapnic respiratory failure. TRIAL REGISTRATION: chictr.org (ChiCTR1800014553). Registered 21 January 2018, http://www.chictr.org.cn.

The Identification of Kabatiella zeae as a Causal Agent of Northern Anthracnose of Sorghum in China and Estimation of Host Resistance.

Sorghum northern anthracnose is a leaf disease affecting sorghum, which results in plant death and substantial yield loss. This study aimed to effectively understand the disease, clarify its biological characteristics, and evaluate the resistance of germplasm resources. A field sample was collected to isolate and purify the pathogen. The pathogen, identified as Kabatiella zeae Narita et Hiratsuka using both morphological and molecular techniques, was further confirmed as the causative agent of northern anthracnose of sorghum following Robert Koch's principles. The results revealed the optimal culture temperature to be 25 °C, preferred dark culture conditions, and the best growth on potato glucose agar medium with sucrose and L-leucine as the optimal carbon and nitrogen sources, respectively. A total of 138 sorghum germplasm resources were inoculated and evaluated using the isolated pathogen, with 20 lines (14.49%) exhibiting high resistance, 18 lines (13.04%) showing disease resistance, 27 lines (19.57%) demonstrating medium resistance, 37 lines (26.81%) being susceptible, and 36 lines (26.09%) classified as highly susceptible. The indoor fungicide screening was conducted through pathogen medium application, and enilconazole, pyraclostrobin, methylthiophanate, and flusilazole were screened for the best fungicide inhibition with a 100% inhibition rate compared with the control. This study provides reference for field pharmaceutical control in sorghum production.

Hydrogen Sulfide Delivery System Based on Salting-Out Effect for Enhancing Synergistic Photothermal and Photodynamic Cancer Therapies.

The simultaneous application of photothermal therapy (PTT) and photodynamic therapy (PDT) offers substantial advantages in cancer treatment. However, their synergistic anticancer efficacy is often limited by tumor hypoxia, and thermotolerance induced by high expression of heat shock proteins (HSP). Fortunately, hydrogen sulfide (H2S), known for its direct cytotoxic effect on tumor cells, has been recognized for its ability to enhance PTT and PDT. The effectiveness of H2S in these therapies is challenged by its low loading efficiency, poor stability, and short diffusion distance. To address these issues, a nanoscale emulsion drop template created through the salting-out effect is employed to construct a robust H2S delivery system. Polydopamine (PDA), chosen for its interfacial polymerization tendency and excellent photothermal conversion rate, is utilized as a carrier for the H2S donor (ADT) and Zinc phthalocyanine (ZnPc) to fabricate a novel nanomedicine termed APZ NPs. The temperature-responsive APZ NPs are designed to release H2S during the PTT process. Elevated H2S levels promoted vasodilation, thereby enhancing the enhanced permeability and retention effect (EPR) of APZ NPs within solid tumors. This strategy effectively alleviated tumor hypoxia by disrupting the mitochondrial respiratory chain and mitigated tumor cell heat tolerance by inhibiting HSP expression.

Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma.

BACKGROUND: Traumatic brain injury (TBI) imposes a substantial societal and familial burden due to its high disability and fatality rates, rendering it a serious public health problem. Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium (POD), which affects their quality of life. Anxiety has been linked to increased POD incidence in some studies, while others have found no correlation. AIM: To investigate the correlation of POD risk factors, preoperative inflammatory factors, and mood disorders in patients with TBI. METHODS: We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023. Patients were grouped as POD and non-POD, according to their POD status, and the general data of the two groups were compared. Inflammatory factor levels were detected preoperatively, and the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to investigate the risk factors associated with POD in these patients. Logistic regression was used to identify the independent risk factors. RESULTS: Twenty-one patients (26.25%) developed POD, including 7, 10, and 4 cases of the excitatory, inhibitory, and mixed types, respectively. There were 59 cases (73.75%) in the non-POD group. Compared with the non-POD group, the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale (GCS) scores before admission, unilateral mydriasis, preoperative hemorrhagic shock, intraventricular hemorrhage (IVH), and postoperative hyperglycemic hyperosmolar disease (P < 0.05). In the POD group, interleukin-6 (IL-6), human tumor necrosis factor-α (TNF-α), myeloperoxidase levels, HAMA, and HAMD scores were higher than those in the non-POD group (all P < 0.05). Logistic multivariate analysis showed that GCS score at admission, IVH, IL-6, TNF-α, HAMA, and HAMD were independent risk factors for POD in patients with TBI (P < 0.05). CONCLUSION: Low GCS score at admission, IVH, elevated IL-6 and TNF-α, other inflammatory indicators, anxiety, and depression, can increase the risk of POD in patients with TBI after surgery.

Design of PDMS/PAN composite membranes with ultra-interfacial stability via layer integration.

The interfacial interaction between the selective layer and porous substrate directly determines the separation performance and service lifetime of functional composite membranes. Till now, almost all reported polymeric selective layers are physically in contact with the substrate, which is unsatisfactory for long-term operation. Herein, we introduced a functional composite membrane with ultra-interfacial stability via layer integration between the polydimethylsiloxane selective layer and polyacrylonitrile substrate, where a facile light-triggered copolymerization achieved their covalent bonding. The critical load for the failure of the selective layer is 45.73 mN when testing the interfacial adhesion, i.e., 5.8 times higher than that before modification and significantly higher than previous reports. It also achieves superior pervaporation performance with a separation factor of 9.54 and membrane flux of 1245.6 g m-2 h-1 feeding a 1000 ppm phenol/water solution at 60 °C that is significantly higher than the same type of polymeric ones. Not limited to pervaporation, such a strategy sheds light on the design of highly stable composite membranes with different purposes, while the facile photo-trigged technique shows enormous scalability.

A Facile Approach to Construct Novel Polyesters as Soft Midblock for Thermoplastic Elastomers.

The development of innovative synthetic strategies to create functional polycaprolactones is highly demanded for advanced material applications. In this contribution, we reported a facile synthetic strategy to prepare a class of CL-based monomers (R-TO) derived from epoxides. They readily polymerize via well-controlled ring-opening polymerization (ROP) to afford a series of polyesters P(R-TO) with high molecular weight (Mn up to 350 kDa). Sequential addition copolymerization of MTO and L-lactide (L-LA) allowed to access of a series of ABA triblock copolymers with composition-dependent mechanical properties. Notably, P(L-LA)100-b-P(MTO)500-b-P(L-LA)100 containing the amorphous P(MTO) segment as a soft midblock and crystalline P(L-LA) domain as hard end block behaved as an excellent thermoplastic elastomer (TPE) with high elongation at break (1438 ± 204%), tensile strength (23.5 ± 1.7 MPa), and outstanding elastic recovery (>88%).

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway.

BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

Design, Synthesis, and Biological Evaluation of Chroman Derivatives as PD-1/PD-L1 Antagonists.

Programmed death-ligand 1 (PD-L1) has emerged as a promising therapeutic target for various cancers due to its crucial role in promoting tumor immune evasion. Here, we report a novel class of chroman-like small-molecule PD-L1 inhibitors exhibiting significant activity in inhibiting the PD-1/PD-L1 interaction. Employing a "ring-close" strategy for conformational restriction, we have achieved compound C27, which demonstrates superior PD-1/PD-L1 inhibitory activity compared to the positive control. Molecular dynamics simulation and binding free energy calculation predict that (R)-C27 with inhibitory activity surpassed (S)-C27. The experimental results from bioassay and X-ray structural analysis corroborate these findings. All these results collectively indicate that (R)-C27 is a promising lead compound deserving further exploration.

Historic dog Furs Unravel the Origin and Artificial Selection of Modern Nordic Lapphund and Elkhound dog Breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Freeze-Thaw Cycle Durability and Mechanism Analysis of Zeolite Powder-Modified Recycled Concrete.

The inferior mechanical performance and freeze-thaw (FT) resistance of recycled concrete are mostly due to the significant water absorption and porosity of recycled coarse particles. In this study, different dosages of zeolite powder were used in recycled concrete. A series of macroscopic tests were used to evaluate the workability and FT durability of zeolite powder-modified recycled concrete (ZPRC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to reveal the micro-mechanisms of FT resistance in ZPRC. The results show that the increase in zeolite powder content leads to a decrease in the slump and water absorption of ZPRC. Additionally, ZPRC with 10% zeolite powder has superior mechanical characteristics and tolerance to FT conditions. The higher strength and FT resistance of the ZPRC can be attributed to the particle-filling effect, water storage function, and pozzolanic reaction of zeolite powder, which results in a denser microstructure. The particle-filling effect of zeolite powder promotes the reduction of surface pores in recycled coarse aggregates (RCAs). The water storage function of zeolite powder can provide water for the secondary hydration of cement particles while reducing the free water content in ZPRC. The pozzolanic reaction of zeolite powder can also promote the generation of hydrated calcium silicate and anorthite, thereby making the microstructure of ZPRC more compact. These results provide theoretical guidance for the engineering application of recycled concrete in cold regions.

Osteoporosis and coronary heart disease: a bi-directional Mendelian randomization study.

Background: Osteoporosis (OP) and cardiovascular disease (CVD) are major global public health issues, especially exacerbated by the challenges of an aging population. As these problems intensify, the associated burden on global health is expected to increase significantly. Despite extensive epidemiological investigations into the potential association between OP and CVD, establishing a clear causal relationship remains elusive. Methods: Instrumental variables were selected from summary statistics of the IEU GWAS database. Five different components of BMD (heel BMD, LS BMD, FA BMD, FN BMD, and TB BMD) were used as OP phenotypes. CHD, MI, and stroke were selected to represent CVD. Multiple analysis methods were used to evaluate the causal relationship between CVD and OP comprehensively. In addition, sensitivity analyses(Cochran's Q test, MR-Egger intercept test, and "leave one out" analysis) were performed to verify the reliability of the results. Results: The MR showed a significant causal relationship between CHD on heel BMD and TB BMD; in the reverse analysis, there was no evidence that OP has a significant causal effect on CVD. The reliability of the results was confirmed through sensitivity analysis. Conclusion: The study results revealed that CHD was causally associated with Heel BMD and TB BMD, while in the reverse MR analysis, the causal relationship between OP and CVD was not supported. This result posits CHD as a potential etiological factor for OP and prompts that routine bone density assessment at traditional sites (forearm, femoral neck, lumbar spine) using DAX may inadequately discern underlying osteoporosis issues in CHD patients. The recommendation is to synergistically incorporate heel ultrasound or DAX for total body bone density examinations, ensuring clinical diagnostics are both precise and reliable. Moreover, these findings provide valuable insights for public health, contributing to the development of pertinent prevention and treatment strategies.

Distinct glutamatergic projections of the posteroventral medial amygdala play different roles in arousal and anxiety.

Sleep disturbance usually accompanies anxiety disorders and exacerbates their incidence rates. The precise circuit mechanisms remain poorly understood. Here, we found that glutamatergic neurons in the posteroventral medial amygdala (MePVGlu) are involved in arousal and anxiety-like behaviors. Excitation of MePVGlu neurons not only promoted wakefulness but also increased anxiety-like behaviors. Different projections of MePVGlu neurons played various roles in regulating anxiety-like behaviors and sleep-wakefulness. MePVGlu neurons promoted wakefulness through the MePVGlu-posteromedial cortical amygdaloid area (PMCo) pathway and the MePVGlu-bed nucleus of the stria terminals (BNST) pathway. In contrast, MePVGlu neurons increased anxiety-like behaviors through the MePVGlu-ventromedial hypothalamus (VMH) pathway. Chronic sleep disturbance increased anxiety levels and reduced reparative sleep, accompanied by the enhanced excitability of MePVGlu-PMCo and MePVGlu-VMH circuits but suppressed responses of glutamatergic neurons in the BNST. Inhibition of the MePVGlu neurons could rescue chronic sleep deprivation-induced phenotypes. Our findings provide important circuit mechanisms for chronic sleep disturbance-induced hyperarousal response and obsessive anxiety-like behavior, and are expected to provide a promising strategy for treating sleep-related psychiatric disorders and insomnia.

Nickel-Catalyzed Enantioselective Carbonyl Addition of Aryl Chlorides and Bromides to Aldehydes.

The Ni-catalyzed enantioselective addition reaction of aryl halides to aldehydes was studied with cyanobis(oxazoline) as chiral ligands and Mn as reductant. Aryl and heteroaryl bromides reacted with phenyl aldehyde at room temperature to produce dibenzyl alcohols in 16-99% yields with 53-92% ees. Moreover, the coupling of phenyl chloride with a variety of aryl, heteroaryl and alkyl aldehydes was demonstrated in the presence of cyanobis(oxazoline)/Ni(II) at 60 oC in generally high yields with moderate enantioselectivities.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination.

BACKGROUND: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions. METHODS: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model. RESULTS: Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression. CONCLUSIONS: We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer.

Ferroptosis, an iron-dependent regulated cell death mechanism, holds significant promise as a therapeutic strategy in oncology. In the current study, we explored the regulatory effects of epigallocatechin gallate (EGCG), a prominent polyphenol in green tea, on ferroptosis and its potential therapeutic implications for non-small cell lung cancer (NSCLC). Treatment of NSCLC cell lines with varying concentrations of EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining. Western blot analyses demonstrated that EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecular changes were accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis. Through small RNA sequencing and RT-qPCR, transfer RNA-derived small RNA 13502 (tsRNA-13502) was identified as a significant target of EGCG action, with its expression being upregulated in NSCLC tissues compared to adjacent non-tumorous tissues. EGCG was found to modulate the ferroptosis pathway by downregulating tsRNA-13502 and altering the expression of key ferroptosis regulators (GPX4/SLC7A11 and ACSL4), thereby promoting the accumulation of iron, MDA, and ROS, and ultimately inducing ferroptosis in NSCLC cells. This study elucidates EGCG's multifaceted mechanisms of action, underscoring the modulation of ferroptosis as a viable therapeutic approach for enhancing NSCLC treatment outcomes.

Unlocking the potential: T1-weighed MRI as a powerful predictor of levodopa response in Parkinson's disease.

BACKGROUND: The efficacy of levodopa, the most crucial metric for Parkinson's disease diagnosis and treatment, is traditionally gauged through the levodopa challenge test, which lacks a predictive model. This study aims to probe the predictive power of T1-weighted MRI, the most accessible modality for levodopa response. METHODS: This retrospective study used two datasets: from the Parkinson's Progression Markers Initiative (219 records) and the external clinical dataset from Ruijin Hospital (217 records). A novel feature extraction method using MedicalNet, a pre-trained deep learning network, along with three previous approaches was applied. Three machine learning models were trained and tested on the PPMI dataset and included clinical features, imaging features, and their union set, using the area under the curve (AUC) as the metric. The most significant brain regions were visualized. The external clinical dataset was further evaluated using trained models. A paired one-tailed t-test was performed between the two sets; statistical significance was set at p < 0.001. RESULTS: For 46 test set records (mean age, 62 ± 9 years, 28 men), MedicalNet-extracted features demonstrated a consistent improvement in all three machine learning models (SVM 0.83 ± 0.01 versus 0.73 ± 0.01, XgBoost 0.80 ± 0.04 versus 0.74 ± 0.02, MLP 0.80 ± 0.03 versus 0.70 ± 0.07, p < 0.001). Both feature sets were validated on the clinical dataset using SVM, where MedicalNet features alone achieved an AUC of 0.64 ± 0.03. Key responsible brain regions were visualized. CONCLUSION: The T1-weighed MRI features were more robust and generalizable than the clinical features in prediction; their combination provided the best results. T1-weighed MRI provided insights on specific regions responsible for levodopa response prediction. CRITICAL RELEVANCE STATEMENT: This study demonstrated that T1w MRI features extracted by a deep learning model have the potential to predict the levodopa response of PD patients and are more robust than widely used clinical information, which might help in determining treatment strategy. KEY POINTS: This study investigated the predictive value of T1w features for levodopa response. MedicalNet extractor outperformed all other previously published methods with key region visualization. T1w features are more effective than clinical information in levodopa response prediction.

Phase Transition and Luminescent Property Change Induced by Different Organic Cations in One-Dimensional Double Perovskites.

Double perovskites (DPs) have attracted attention in the field of luminescence due to their inherent broadband emission of self-trapping excitons. In this work, we choose [(CH3)3NCH2CHCH2]+ and [CH3CHOHCH2NH2]+ as organic cations to synthesize two new organic-inorganic hybrid DPs, [(CH3)3NCH2CHCH2]2KInCl6 (1) and [CH3CHOHCH2NH2]2KInCl6 (2). The [KCl6]3- and [InCl6]3- octahedra are interchangeably connected by sharing two opposite faces, forming a one-dimensional coordination chain. Each K atom coordinates with six chlorine atoms in 1, while it coordinates with two oxygen atoms in addition to the six chlorine atoms in 2. The coordination between ions K and O in compound 2 may have significantly reduced its luminescence. As a result, compound 1 shows bright-yellow light with a quantum yield of more than 90%, while 2 shows weak blue light with a quantum yield of only 0.98%. In addition, different from no phase transition found in 2, 1 undergoes a reversible phase transition at 324/307 K in the heating-cooling cycle. Through structural and spectral analysis and density functional theory calculation, we conclude that the larger degree of [InCl6]3- octahedral distortion and the larger anion distance (In···In) also cause the PLQY of compound 1 to be higher than that of compound 2.

HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model. Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.

Efficacy and safety of brivudine for the treatment of herpes zoster: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine. METHODS: Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted. RESULTS: The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05). CONCLUSIONS: Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.