Advanced ethylene-absorbing and cushioning depending on the 3D porous-structured fruit packaging: Toward polyurethane foam manipulation using zein and soybean oil polyol substrates.

Fruits are essential sources of nutrients in our daily diet; however, their spoilage is often intensified by mechanical damage and the ethylene phytohormone, resulting in significant economic losses and exacerbating hunger issues. To address these challenges, this study presented a straightforward in situ synthesis protocol for producing Z/SOPPU foam, a 3D porous-structured fruit packaging. This innovative packaging material offered advanced ethylene-adsorbing and cushioning capabilities achieved through stirring, heating, and standing treatments. The results demonstrated that the Z/SOPPU foam, with its porous structure, served as an excellent packaging material for fruits, maintaining the intact appearance of tomatoes even after being thrown 72 times from a height of 1.5 m. Additionally, it exhibited desirable hydrophobicity (contact angle of 114.31 ± 0.82°), degradability (2.73 ± 0.88 % per 4 weeks), and efficient ethylene adsorption (adsorption rate of 13.2 ± 1.7 mg/m3/h). These remarkable characteristics could be attributed to the unique 3D micron-porous configuration, consisting of soybean oil polyol polyurethane foam for mechanical strain cushioning and zein for enhanced ethylene adsorption efficiency. Overall, this research offers an effective and original approach to the rational design and fabrication of advanced bio-based fruit packaging.

An Alkaline Nanocage Continuously Activates Inflammasomes by Disrupting Multiorganelle Homeostasis for Efficient Pyroptosis.

Pyroptosis has garnered increasing attention because of its ability to trigger robust antitumor immunity. Pyroptosis is initiated by the activation of inflammasomes, which are regulated by various organelles. The collaboration among organelles offers several protective mechanisms to prevent activation of the inflammasome, thereby limiting the induction of efficient pyroptosis. Herein, a multiorganelle homeostasis disruptor (denoted BLL) is constructed by encapsulating liposomes and bortezomib (BTZ) within a layered double hydroxide (LDH) nanocage to continuously activate inflammasomes for inducing efficient pyroptosis. In lysosomes, the negatively charged liposomes are released to recruit the NLRP3 inflammasomes through electrostatic interactions. ER stress is induced by BTZ to enhance the activation of the NLRP3 inflammasome. Meanwhile, the BLL nanocage exhibited H+-scavenging ability due to the weak alkalinity of LDH, thus disrupting the homeostasis of the lysosome and alleviating the degradation of the NLRP3 inflammasome by lysosomal-associated autophagy. Our results suggest that the BLL nanocage induces homeostatic imbalance in various organelles and efficient pyroptosis. We hope this work can provide new insights into the design of an efficient pyroptosis inducer by disrupting the homeostatic balance of multiple organelles and promote the development of novel antineoplastic platforms.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Fortifying nematode resistance through susceptibility gene inactivation.

The predominant genetic defense mechanism against soybean cyst nematode (SCN) in 95% of the North America market is under threat by virulent SCN populations. Usovsky et al. identified GmSNAP02 as an SCN susceptibility gene through fine-mapping of unique bi-parental populations. Loss-of-function of GmSNAP02 confers enhanced resistance to more virulent SCN.

Cisplatin-activated and hemoglobin-mediated injectable hydrogel system for antitumor chemodynamic and chemotherapy.

Low specificity and hypoxia-induced drug resistance are significant challenges in traditional cancer treatment. To enhance the anticancer efficacy, an injectable hydrogel system is developed through the formation of dynamic covalent bonds in hyaluronic acid, allowing for localized controlled release of drugs. This system also utilizes double-stranded DNA sequences for the intercalation delivery of the chemotherapeutic drug, enabling a multifaceted approach to therapy. Cisplatin not only serves as a chemotherapy drug but also acts as a catalyst for chemodynamic therapy (CDT) to initiate CDT cascades by creating hydrogen peroxide for the Fenton reaction. Hemoglobin, enclosed in PLGA nanoparticles, provides ferrous ions that react with hydrogen peroxide in an acidic environment, yielding hydroxyl radicals that induce cancer cell death. Additionally, oxygen released from hemoglobin mitigates hypoxia-induced chemoresistance, bolstering overall anticancer efficacy. Results demonstrate the shear-thinning properties and injectability of the hydrogel. Cisplatin elevates intracellular hydrogen peroxide levels in tumor cells, while hemoglobin efficiently releases ferrous ions and generates reactive oxygen species (ROS) in the presence of hydrogen peroxide. In in vitro and in vivo study, the combinational use of chemo- and chemodynamic therapies achieves a synergistic anticancer effect on combating glioblastoma. In summary, our CDT-based hydrogel, activated by endogenous cues and mediated by chemo drugs, spontaneously produces ROS and ameliorates the adverse tumor microenvironment with rational and selective antitumor strategies.

[Prokaryotic Expression and Bioinformatic Analysis of Rv3432c From Mycobacterium tuberculosis]. / ç»“æ ¸åˆ†æžæ†èŒRv3432cè›‹ç™½çš„åŽŸæ ¸è¡¨è¾¾ä¸Žç”Ÿç‰©ä¿¡æ¯å­¦åˆ†æž.

Objective: To express the protein enconded by the Rv3432c gene of Mycobacterium tuberculosis (M.tb) in vitro by prokaryotic expression, to analyze the structure of the Rv3432c protein by using bioinformatics software, and to explore for new drug targets against M.tb. Methods: The Rv3432c gene was amplified by PCR using the genomic DNA of the inactivated M.tb strain H37Rv as the template and a recombinant plasmid was constructed with the expression vector pET-28a. The expression products were analyzed by SDS-PAGE and purified using affinity chromatography. The biological properties of Rv3432c were analyzed with Protparam, the Pfam online tool, SOMPA, Protscale, TMHMM Signalp 6.0, NetPhos3.1, SUMOsp 2.0, and SWISS-MODEL. Results: pET-28a-Rv3432c recombinant plasmid sequencing results were fully consistent with those of the target gene. SDS-PAGE analysis showed that the fusion protein existed in the form of a soluble protein with a relative molecular mass of about 55×103, which matched the expected size. ProtParam analysis showed that the Rv3432c protein was hydrophilic (showing a GRAVY value of －0.079). Rv3432c was a protein with no transmembrane structural domains or signal peptide. The secondary structure of Rv3432c mainly consisted of random coils (39.78%) and α-helix (39.57%) and was relatively loosely structured. Conclusion: We successfully constructed a prokaryotic expression plasmid of the Rv3432c protein and analyzed its structure using bioinformatics, laying the foundation for further research on the role of Rv3432c in the pathogenesis and progression of tuberculosis as well as the identification of new drug targets against M.tb.

Clinical Application of Botulinum Toxin A on Nasal Reconstruction with Expanded Forehead Flap for Asian Patients.

BACKGROUND: Because of its unique advantages, frontal expansion has become a common tool for Asian nasal reconstruction, but it has the limitations of prolonging the duration and pain in the expansion area. Based on the fact that the denervation effect of botulinum toxin type A (BTX-A) has been widely used in the reconstruction of superficial organs, we hypothesized that BTX-A would shorten the length of nasal reconstruction sequence and alleviate the discomfort of patients. METHODS: A comparative retrospective study was conducted of consecutive patients underwent sequential treatment of nasal reconstruction between June 2010 and July 2012. Data on demographics, BTX-A injection plan and expansion duration were collected and analyzed. Phased pain intensity outcomes were evaluated by visual analogue scale (VAS). Photographs were collected during the follow-up period. RESULTS: Thirty patients were enrolled in the study; 15 (50%) with and 15 (50%) without BTX-A pre-injection. Demographic data were homogeneous. The duration of the observation group (BTX-A pretreated) (133.87 ± 13.64 days) was significantly shortened versus the control group (164.27 ± 14.08 days, P<0.001). At the initial stage, no significant difference was found in the VAS scores (P=0.64). At the medium stage, the VAS score of the observation group (2.07 ± 0.80) was significantly lower than the control group (3.00 ± 0.53, P<0.01). At the terminal stage, the VAS score of the observation group (1.93 ± 0.59) was significantly lower than the control group (2.73 ± 0.70) but with a narrower disparity. CONCLUSION: Pre-injection of BTX-A is effective in shortening the duration of the expansion phase, as well as relieving the pain associated with expansion. LEVEL OF EVIDENCE IV: The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

Effect of intraoperative dexmedetomidine on recovery of gastrointestinal function after caesarean section undergoing spinal and epidural anesthesia: A randomized, double blind, placebo-controlled clinical trial.

OBJECTIVE: Gastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section. STUDY DESIGN: 220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 µg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 µg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days). RESULTS: Modified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S. CONCLUSION: Intraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section.

[Corrigendum] Long non­coding RNA H19 regulates LASP1 expression in osteosarcoma by competitively binding to miR­29a­3p.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the cell invasion assay experiments shown in Fig. 2D on p. 5, there appeared to be an overlapping section of data comparing between the Sao­2/Control and MG­63/siH19 panels, such that these data had been derived from the same original source where the panels were intended to portray the results from differently performed epxeriments. Upon examining their original data, the authors have realized that, in Fig. 2D, an inadvertent error was made in the copying and pasting of the two groups of pictures, resulting in the image belonging to the Saos­2 cell experiment being mistakenly pasted as the image for the MG­63 cell experiment. The authors carefully checked the original pictures and the experimental record, and found that the two groups of cells were close to the same morphology. The corrected version of Fig. 2, containing data from an alternatively performed experiment for Fig. 2D, is shown on the next page. Note that the error did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 46: 207, 2021; DOI: 10.3892/or.2021.8158].

Habitat-Based Radiomics for Predicting EGFR Mutations in Exon 19 and 21 From Brain Metastasis.

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

Anisotropic power-law viscoelasticity of living cells is dominated by cytoskeletal network structure.

During physiological and pathological processes, cells experience significant morphological alterations with the re-arrangement of cytoskeletal filaments, resulting in anisotropic viscoelasticity. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. We investigate how cell shape affects its creep responses in longitudinal and perpendicular directions. It is shown that cells exhibit power-law rheological behavior in both longitudinal and perpendicular directions under step stress, with a more solid-like behavior along the longitudinal direction. We reveal that the cell volume and cytoskeletal filament orientation, which have been neglected in most existing models, play a critical role in regulating cellular anisotropic viscoelasticity. The stiffness of the cell in both directions increases linearly with increasing its aspect ratio, due to the decrease of cell volume. Moreover, the increase in the cell's aspect ratio produces the aggregation of cytoskeletal filaments along the longitudinal direction, resulting in higher stiffness in this direction. It is also shown that the increase in cell's aspect ratio corresponds to a process of cellular ordering, which can be quantitatively characterized by the orientational entropy of cytoskeletal filaments. In addition, we present a simple yet robust method to establish the relationship between cell's aspect ratio and cell volume, thus providing a theoretical framework to capture the anisotropic viscoelastic behavior of cells. This study suggests that the structure-based cell models may be further developed to investigate cellular rheological responses to external mechanical stimuli and may be extended to the tissue scale. STATEMENT OF SIGNIFICANCE: The viscoelastic behaviors of cells hold significant importance in comprehending the roles of mechanical forces in embryo development, invasion, and metastasis of cancer cells. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. Our study highlights the crucial role of previously neglected factors, such as cell volume and cytoskeletal filament orientation, in regulating cellular anisotropic viscoelasticity. We further propose an orientational entropy of cytoskeletal filaments to quantitatively characterize the ordering process of cells with increasing aspect ratios. Moreover, we derived the analytical interrelationships between cell aspect ratio, cell stiffness, cell volume, and cytoskeletal fiber orientation. This study provides a theoretical framework to describe the anisotropic viscoelastic mechanical behavior of cells.

The Impact of Transcriptional Profiling Cadherin Family and Therapeutic Approaches of Gastric Cancer: A Translational Outlook on Multi-omics Data Analysis.

The classical cadherin gene has been linked to a variety of human malignancies, including gastric cancer. However, the link between cadherin genes and gastric cancer outcome is still unclear. This study used multi-omics data to examine the cadherin genes that were differentially regulated in gastric cancer. Differential expression of genes, epigenetic, molecular alterations, and protein expression analyses was conducted. Male SD rats were given N-methyl-N-nitrosourea (MNU) to induce stomach carcinoma in order to verify the activation of cadherin genes. CDH5, CDH6, CDH11, and CDH24 levels were found to be considerably higher in gastric cancer and may serve as useful indicators of stomach adenocarcinoma (STAD). Cadherin genes with variable expression had considerably more promoter methylation in cancers than in normal tissues. In individuals with gastric cancer, high expression of these cadherin genes was related to lower total mortality and disease-free survival rates. Furthermore, compared to normal rats, gastric cancer-induced rats had significantly higher expression and distribution of CDH5, CDH6, CDH11, and CDH24. This study sheds new light on the diagnosis and prognosis of gastric cancer by identifying potential prognostic markers such as CDH5, CDH6, CDH11, and CDH24. The multi-omics approach provided a potential tool for target-based therapy by accurately predicting the outcome of stomach cancer. Researchers may gain more knowledge about the role of cadherin genes in the development and dissemination of tumors to the activated rat model of gastric cancer.

Whole-genome sequencing of allotetraploid bermudagrass reveals the origin of Cynodon and candidate genes for salt tolerance.

Bermudagrass (Cynodon dactylon) is a globally distributed, extensively used warm-season turf and forage grass with high tolerance to salinity and drought stress in alkaline environments. However, the origin of the species and genetic mechanisms for salinity tolerance in the species are basically unknown. Accordingly, we set out to study evolution divergence events in the Cynodon genome and to identify genes for salinity tolerance. We developed a 604.0 Mb chromosome-level polyploid genome sequence for bermudagrass 'A12359' (n = 18). The C. dactylon genome comprises 2 complete sets of homoeologous chromosomes, each with approximately 30 000 genes, and most genes are conserved as syntenic pairs. Phylogenetic study showed that the initial Cynodon species diverged from Oropetium thomaeum approximately 19.7-25.4 million years ago (Mya), the A and B subgenomes of C. dactylon diverged approximately 6.3-9.1 Mya, and the bermudagrass polyploidization event occurred 1.5 Mya on the African continent. Moreover, we identified 82 candidate genes associated with seven agronomic traits using a genome-wide association study, and three single-nucleotide polymorphisms were strongly associated with three salt resistance genes: RAP2-2, CNG channels, and F14D7.1. These genes may be associated with enhanced bermudagrass salt tolerance. These bermudagrass genomic resources, when integrated, may provide fundamental insights into evolution of diploid and tetraploid genomes and enhance the efficacy of comparative genomics in studying salt tolerance in Cynodon.

An ATPase-Mimicking MXene nanozyme pharmacologically breaks the ironclad defense system for ferroptosis cancer therapy.

Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.

Tunneled Paranasal Augmentation Using Diced Autologous Costal Cartilage in Asian Rhinoplasty: A Comparative Study.

Due to the prevalence of anterior maxilla dysplasia in Asian population, paranasal concavity is a common accompaniment to low nose, but its impact on facial harmonization is often underestimated. A retrospective comparative study was conducted on patients diagnosed as low nose with paranasal concavity between June 2017 and June 2021, with a total of 56 patients followed up successfully. The control and observation groups were established according to whether the paranasal augmentation was performed. Demographic data were collected. Cosmetic enhancement was quantitatively evaluated by sagittal planimetry, establishing related anatomical landmarks and measuring columella base prominence (CBP) and alar base prominence (ABP). Subjective evaluation concluded the patient-reported satisfaction (FACE-Q-Rhinoplasty Module and Facial Appearance Module) and the third-party physician assessment (Global Aesthetic Improvement Scale, GAIS).Significant improvements in CBP and ABP were reported both in the control and the observation group (p < 0.01). In postoperative intergroup comparisons, the observation group was superior to the control group regarding ABP values (2.5 ± 0.75 degrees, p < 0.01), FACE-Q-Facial scores (7.49 ± 3.70, p < 0.05), and GAIS scores (p < 0.05). However, no statistical difference was found in CBP values and FACE-Q-Rhinoplasty scores. Paranasal augmentation-related complications included asymmetry of alar bases (6.9%) and facial or intraoral foreign body sensation (34.5%). This study affirmed that paranasal augmentation using diced costal cartilage in rhinoplasty is a safe procedure effective in remedying paranasal concavity and improving facial satisfaction. LEVEL OF EVIDENCE:: IV.

Improved Prediction of Epidermal Growth Factor Receptor Status by Combined Radiomics of Primary Nonsmall-Cell Lung Cancer and Distant Metastasis.

OBJECTIVES: This study aimed to investigate radiomics based on primary nonsmall-cell lung cancer (NSCLC) and distant metastases to predict epidermal growth factor receptor (EGFR) mutation status. METHODS: A total of 290 patients (mean age, 58.21 ± 9.28) diagnosed with brain (BM, n = 150) or spinal bone metastasis (SM, n = 140) from primary NSCLC were enrolled as a primary cohort. An external validation cohort, consisting of 69 patients (mean age, 59.87 ± 7.23; BM, n = 36; SM, n = 33), was enrolled from another center. Thoracic computed tomography-based features were extracted from the primary tumor and peritumoral area and selected using the least absolute shrinkage and selection operator regression to build a radiomic signature (RS-primary). Contrast-enhanced magnetic resonance imaging-based features were calculated and selected from the BM and SM to build RS-BM and RS-SM, respectively. The RS-BM-Com and RS-SM-Com were developed by integrating the most important features from the primary tumor, BM, and SM. RESULTS: Six computed tomography-based features showed high association with EGFR mutation status: 3 from intratumoral and 3 from peritumoral areas. By combination of features from primary tumor and metastases, the developed RS-BM-Com and RS-SM-Com performed well with areas under curve in the training (RS-BM-Com vs RS-BM, 0.936 vs 0.885, P = 0.177; RS-SM-Com vs RS-SM, 0.929 vs 0.843, P = 0.003), internal validation (RS-BM-Com vs RS-BM, 0.920 vs 0.858, P = 0.492; RS-SM-Com vs RS-SM, 0.896 vs 0.859, P = 0.379), and external validation (RS-BM-Com vs RS-BM, 0.882 vs 0.805, P = 0.263; RS-SM-Com vs RS-SM, 0.865 vs 0.816, P = 0.312) cohorts. CONCLUSIONS: This study indicates that the accuracy of detecting EGFR mutations significantly enhanced in the presence of metastases in primary NSCLC. The established radiomic signatures from this approach may be useful as new predictors for patients with distant metastases.

Interleukin-10: a novel metabolic inducer of macrophage differentiation and subsequently contributing to improved pregnancy outcomes of mice by orchestrating oxidative phosphorylation metabolism.

Metabolism regulates the phenotype and function of macrophages. After recruitment to local tissues, monocytes are influenced by the local microenvironment and differentiate into various macrophages depending on different metabolic pathways. However, the metabolic mechanisms underlying decidual macrophage differentiation remain unknown. Interleukin-10 (IL-10) is an important decidual macrophage inducer and promotes oxidative phosphorylation (OXPHOS) of bone marrow-derived macrophages. In this study, we mainly investigate the metabolic changes involved in IL-10 generated macrophages from monocytes using in vitro models. We demonstrate that exposure of monocytes (either peripheral or THP-1) to IL-10 altered the phenotype and function of resultant macrophages that is linked with OXPHOS changes. IL-10 enhanced the mitochondrial complex I and III activity of THP-1 cell-differentiated macrophages and increased the mitochondrial membrane potential, intracellular adenosine triphosphate, and reactive oxygen species levels. OXPHOS blockage with oligomycin changed the cell morphology of IL-10-generated macrophages and the expression levels of cytokines, such as transforming growth factor beta, tumor necrosis factor-alpha, interferon gamma, and IL-10, apart from changes in the expression level of the surface markers CD206, CD209, and CD163. Moreover, in vivo IL-10 administration reduced the lipopolysaccharide (LPS)-induced embryo resorption rate, and this effect was diminished when OXPHOS was inhibited, demonstrating that OXPHOS is important for the improved pregnancy outcomes of IL-10 in LPS-induced abortion-prone mice. Our findings provide deep insights into the roles of IL-10 in macrophage biology and pregnancy maintenance. Nevertheless, the direct evidence that OXPHOS is involved in decidual macrophage differentiation or not needs further investigations.

Hybrid transformer convolutional neural network-based radiomics models for osteoporosis screening in routine CT.

OBJECTIVE: Early diagnosis of osteoporosis is crucial to prevent osteoporotic vertebral fracture and complications of spine surgery. We aimed to conduct a hybrid transformer convolutional neural network (HTCNN)-based radiomics model for osteoporosis screening in routine CT. METHODS: To investigate the HTCNN algorithm for vertebrae and trabecular segmentation, 92 training subjects and 45 test subjects were employed. Furthermore, we included 283 vertebral bodies and randomly divided them into the training cohort (n = 204) and test cohort (n = 79) for radiomics analysis. Area receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were applied to compare the performance and clinical value between radiomics models and Hounsfield Unit (HU) values to detect dual-energy X-ray absorptiometry (DXA) based osteoporosis. RESULTS: HTCNN algorithm revealed high precision for the segmentation of the vertebral body and trabecular compartment. In test sets, the mean dice scores reach 0.968 and 0.961. 12 features from the trabecular compartment and 15 features from the entire vertebral body were used to calculate the radiomics score (rad score). Compared with HU values and trabecular rad-score, the vertebrae rad-score suggested the best efficacy for osteoporosis and non-osteoporosis discrimination (training group: AUC = 0.95, 95%CI 0.91-0.99; test group: AUC = 0.97, 95%CI 0.93-1.00) and the differences were significant in test group according to the DeLong test (p < 0.05). CONCLUSIONS: This retrospective study demonstrated the superiority of the HTCNN-based vertebrae radiomics model for osteoporosis discrimination in routine CT.

Flexible scaffold-based cheminformatics approach for polypharmacological drug design.

Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2AR to act as an antagonist and a "stretching-up" binding pose at 5-HT1AR to function as an agonist. IHCH-7179 demonstrated promising results in alleviating cognitive deficits and psychoactive symptoms in mice by blocking 5-HT2AR for psychoactive symptoms and activating 5-HT1AR to alleviate cognitive deficits. By analyzing aminergic receptor structures, we identified two featured motifs, the "agonist filter" and "conformation shaper," which determine ligand binding pose and predict activity at aminergic receptors. With these motifs, FSCA can be applied to the design of polypharmacological ligands at other receptors.