Combining Deep Learning and Radiomics for Automated, Objective, Comprehensive Bone Mineral Density Assessment From Low-Dose Chest Computed Tomography.

RATIONALE AND OBJECTIVES: To develop an intelligent diagnostic model for osteoporosis screening based on low-dose chest computed tomography (LDCT). The model incorporates automatic deep-learning thoracic vertebrae of cancellous bone (TVCB) segmentation model and radiomics analysis. MATERIALS AND METHODS: A total of 442 participants who underwent both LDCT and quantitative computed tomography (QCT) examinations were enrolled and were randomly allocated to the training, internal testing, and external testing cohorts. The TVCB automatic segmentation model was trained using VB-Net. The accuracy of the segmentation was evaluated using the Dice coefficient. Predictive models for assessing bone mineral density (BMD) were constructed utilizing radiomics analysis based on automatic segmentation (ASeg model) and manual segmentation (MSeg model), respectively. The BMD predictive model based on ASeg and MSeg included the identification of normal and abnormal BMD (first-level model), and osteopenia and osteoporosis (second-level model). The diagnostic performance of the radiomics models were evaluated using the area under the curve (AUC), sensitivity and specificity. RESULTS: The Dice coefficients of the TVCB segmentation model in the internal and external testing cohorts were found to be 0.988 ± 0.014 and 0.939 ± 0.034, respectively. In the first-level model, the AUC of the ASeg model exhibited comparable performance to that of the MSeg model for both the internal (0.985 vs. 0.946, P = 0.080) and external (0.965 vs. 0.955, P = 0.724) testing cohorts. Similarly, in the second-level model, the AUC of the ASeg model was found to be comparable to that of the MSeg model for both the internal (0.933 vs. 0.920, P = 0.794) and external (0.907 vs. 0.892, P = 0.805) testing cohorts. CONCLUSION: A fully automated pipeline for TVCB segmentation and BMD assessment with radiomics analysis can be used for opportunistic BMD screening in chest LDCT.

Role of leptin in the pathophysiology of preeclampsia.

Preeclampsia (PE) is a severe pregnancy complication. The exact pathogenesis of PE remains unclear, but it is related to immune, inflammatory, circulatory, and oxidative stress factors. Leptin is a protein involved in these processes and is essential for maintaining a normal pregnancy and healthy fetal growth. Abnormal increases in leptin levels have been observed in the peripheral blood and placenta of patients with PE. Disturbances in leptin can affect the proliferation and hypertrophy of vascular smooth muscle cells, which are important for placentation. Leptin also regulates arterial tension and trophoblast function in pregnant women. In addition, consistently high levels of leptin are linked to hyperactive inflammation and oxidative stress reactions in both patients with PE and animal models. This review focuses on the role of leptin in the pathophysiology of PE and elucidates its potential mechanisms.

CO2/CH4 separation performance of SiO2/PES composite membrane prepared by gas phase hydrolysis and grafting coating in gas-liquid membrane contactor: A comparative study.

The gas-liquid membrane contactor (GLMC) is a new and promising kind of gas separation technique, but still exhibits limitations, especially in membrane performance. In order to solve the above problems, we fabricated and characterized novel OH/SiO2/PES composite membranes using gas phase hydrolysis and graft coating methods, respectively. In the preparation process, whether to use alkali to pretreat the membrane was used as an evaluation index. The CO2/CH4 separation performance was tested using the modified OH/SiO2/PES hollow fiber membrane as the membrane contactor in GLMC. In the experiment, we conducted a single factor experiment with diethanolamine (DEA) as the adsorbent to analyze the effect of the flow rate and concentration of DEA on the separation of CO2/CH4. The collected gas had a CH4 content of 99.92% and a CO2 flux of 10.1059 × 10-3 mol m-2 s-1 while DEA at a concentration of 1 mol/L was flowing at a rate of 16 L/h. The highest separation factor occurred at this moment, which was 833.67. Overall, the CO2/CH4 separation performance in GLMC was enhanced with the use of the fluorinated OH/SiO2/PES composite membrane.

Morphological analysis and classification of posterior malleolar fractures based on CT scans.

OBJECTIVES: The aim of the study was to propose a classification system of posterior malleolar fractures by fracture lines with the use of CT scans, including 3D CT reconstruction, which can better understand morphological characteristics, analyze the mechanism and guide the surgeon to choose the optimal approach and fixation. METHODS: Patients with OTA/AO type 44 fractures involving the posterior malleolus and preoperative CT scans were included. We retrospectively analyzed 128 consecutive patients with posterior malleolar fractures from January 2013 to December 2019 at our institution. CT data were loaded into Mimics software (V20.0, Materialize), in which 3D CT reconstruction, morphological analysis and data measurements were made. RESULTS: Based on the number of fracture lines in 128 consecutive patients, posterior malleolar fractures were classified into three types: type 1 with a single fracture line, type 2 with double fracture lines and type 3 with multiple fracture lines. According to the distribution of the fracture line, type 1 was divided into types 1A, 1B and 1C, and type 2 was divided into types 2A, 2B and 2C. The fracture line from the fibular notch to the posterior rim of the distal tibia was defined as type 1A, and the fracture line to the medial malleolus was defined as type 1B. Type 1C was a small fragment in the posterior rim of the distal tibia. Type 2A was regarded as type 1A with type 1C. It was considered type 2B because another fracture line started from the fracture line of type 1A and extended to the medial malleolus. In type 2C, we could see that the double fracture lines were all from the fibular notch to the posterior rim of the distal tibia and did not cross. Type 3 fractures were comminuted fractures with multiple fracture lines. CONCLUSION: The morphology of posterior malleolar fractures, involvement of the fibular notch, or the medial malleolus can be obviously assessed by our classification system. We found the relation of the injury mechanism between type 1 and type 2 by comparing the area of the fragment. We have indicated that each type of fracture corresponds to its associated injury mechanism and which surgical approach and fixation can be chosen.

Comprehensive evaluation of aroma and taste properties of different parts from the wampee fruit.

Wampee is a tropical fruit having high medicinal value. To fully realize the fruit's potential, it is essential to reveal the flavor characteristics. In this study, a comprehensive analysis of the aroma and taste profiles of different parts from the wampee fruit was conducted. The aroma profile was analyzed by E-nose, and 67 volatile components were identified through HS-SPME-GC-MS. Among them, 11 were considered as crucial compounds. Additionally, 42 volatile components were identified by HS-GC-IMS, with 22 compounds showing a variable importance in projection scores greater than 1.0. Moreover, the taste profile and representative compounds were analyzed by E-tongue and HPLC, and 12 compounds were considered as important taste contributors based on taste activity value. These findings shed light on the various compounds responsible for the unique aroma and taste of the wampee fruit, providing theoretical foundation for exploring ways for its comprehensive utilization and development.

Effect of flexible sigmoidoscopy-based screening on colorectal cancer incidence and mortality: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Our objective was to estimate the effect of flexible sigmoidoscopy (FS)-based screening on colorectal cancer (CRC) incidence and mortality by conducting an updated meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, Web of Science, Embase, and Cochrane Library searched for RCTs from database inception to December 2022. The methodological quality of the RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.4 was used for this meta-analysis. RESULTS: Four RCTs involving 457, 871 patients were included. This meta-analysis revealed that FS-based screening was associated with a 20% relative risk reduction in CRC incidence [RR = 0.80; 95% CI (0.75, 0.86); P < 0.00001], and a 24% reduction in CRC mortality [RR = 0.76; 95% CI (0.70, 0.82); P < 0.00001]. In addition, this meta-analysis revealed that FS-based screening reduced the incidence[RR = 0.68; 95% CI (0.60, 0.77); P < 0.00001] and mortality[RR = 0.64; 95% CI (0.49, 0.83); P = 0.0007] of distal CRC, but had no significant effect on proximal colon cancer. CONCLUSION: FS-based screening appeared to be effective in reducing distal CRC incidence and mortality in patients at average risk compared to no intervention, but had no significant effect on proximal colon cancer.

Methylated tumor suppressor gene SCARA5 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma.

Background: SCARA5 may play an important role in nasopharyngeal carcinoma. Materials & methods: PCR and immunohistochemistry were used to detect the expression and promoter methylation of SCARA5. Cell proliferation assays, spheroid culture, flow cytometry analysis, Transwell assays and xenotransplantation tests were utilized to determine the functional effects of SCARA5. RNA-sequencing, western blotting, immunofluorescence and dual-luciferase reporter assays were used to assess SCARA5-mediated outcomes. Results: SCARA5 was downregulated by promoter methylation. Overexpression of SCARA5 inhibited cell migration, invasion and proliferation. SCARA5 enhanced nasopharyngeal carcinoma cell sensitivity to chemotherapy with cisplatin and 5-fluorouracil. SCARA5 drives tumor apoptosis by downregulating HSPA2. Conclusion: SCARA5 may be a useful clinical marker in nasopharyngeal carcinoma.

An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression.

Anti-interleukin-17 (IL-17) therapy has been used in various autoimmune diseases. However, the efficacy is unexpectedly limited in several IL-17-associated diseases, and the mechanism of limited efficacy remains unclear. Here, we show that a molecular complex containing the adaptor molecule Act1 and tyrosine phosphatase SHP2 mediated autonomous IL-17R signaling that accelerated and sustained inflammation. SHP2, aberrantly augmented in various autoimmune diseases, was induced by IL-17A itself in astrocytes and keratinocytes, sustaining chemokine production even upon anti-IL-17 therapies. Mechanistically, SHP2 directly interacted with and dephosphorylated Act1, which replaced Act1-TRAF5 complexes and induced IL-17-independent activation of IL-17R signaling. Genetic or pharmacologic inactivation of SHP2, or blocking Act1-SHP2 interaction, paralyzed both IL-17-induced and IL-17-independent signaling and attenuated primary or relapsing experimental autoimmune encephalomyelitis. Therefore, Act1-SHP2 complexes mediate an alternative pathway for autonomous activation of IL-17R signaling, targeting which could be a therapeutic option for IL-17-related diseases in addition to current antibody therapies.

Echinacoside alleviates airway remodeling and inflammation in an ovalbumin-induced neonatal mouse model of asthma by modulating the SIRT1-NF-κB pathway.

PURPOSE: Echinacoside (ECH) has been reported to have anti-inflammatory and anti-immune effects, and may be effective for treating asthma. This study aimed to investigate the effect of ECH on asthma. METHODS: A mouse model of asthma was established by ovalbumin (OVA) induction, and the effect of ECH on airway remodeling in mice was evaluated using the Periodic Acid-Schiff stain and enzyme-linked immunosorbent serologic assay (ELISA). Additionally, the effect of ECH on collagen deposition in asthmatic mice was assessed using Western blotting (WB) analysis, and response to airway inflammation was evaluated by ELISA. The signaling pathway regulated by ECH was also investigated using WB. RESULTS: Our findings demonstrated that ECH restored OVA-induced increase in mucin, -immunoglobulin E, and respiratory resistance. ECH also alleviated OVA-induced collagen -deposition, including collagen I, collagen III, alpha smooth muscle actin, and epithelial (E)-cadherin. Moreover, ECH restored the elevated levels of interleukin (IL)-13, IL-17, and the increased -number of macrophages, eosinophils, lymphocytes, and neutrophills induced by OVA. ECH mainly exerted its regulatory effects by modulating the silent mating type information regulation 2 homolog 1 (Sirtuin 1/SIRT1)-nuclear factor kappa B (NF-κB) signaling pathway in the mouse models of asthma. CONCLUSION: This study highlights the therapeutic potential of ECH for attenuating airway remodeling and inflammation in an OVA-induced neonatal mouse model of asthma through the modulation of SIRT1/NF-κB pathway.

Dopamine release and negative valence gated by inhibitory neurons in the laterodorsal tegmental nucleus.

GABAergic neurons in the laterodorsal tegmental nucleus (LDTGABA) encode aversion by directly inhibiting mesolimbic dopamine (DA). Yet, the detailed cellular and circuit mechanisms by which these cells relay unpleasant stimuli to DA neurons and regulate behavioral output remain largely unclear. Here, we show that LDTGABA neurons bidirectionally respond to rewarding and aversive stimuli in mice. Activation of LDTGABA neurons promotes aversion and reduces DA release in the lateral nucleus accumbens. Furthermore, we identified two molecularly distinct LDTGABA cell populations. Somatostatin-expressing (Sst+) LDTGABA neurons indirectly regulate the mesolimbic DA system by disinhibiting excitatory hypothalamic neurons. In contrast, Reelin-expressing LDTGABA neurons directly inhibit downstream DA neurons. The identification of separate GABAergic subpopulations in a single brainstem nucleus that relay unpleasant stimuli to the mesolimbic DA system through direct and indirect projections is critical for establishing a circuit-level understanding of how negative valence is encoded in the mammalian brain.

Evaluation of postoperative recovery: past, present and future.

Postoperative recovery, as a window to observe perioperative treatment effect and patient prognosis, is a common outcome indicator in clinical research and has attracted more and more attention of surgeons and anaesthesiologists. Postoperative recovery is a subjective, multidimensional, long-term, complex process, so it is unreasonable to only use objective indicators to explain it. Currently, with the widespread use of patient-reported outcomes, various scales become the primary tools for assessing postoperative recovery. Through systematic search, we found 14 universal recovery scales, which have different structures, contents and measurement properties, as well as their own strengths and weaknesses. We also found that it is urgently necessary to perform further researches and develop a scale that can serve as the gold universal standard to evaluate postoperative recovery. In addition, with the rapid development of intelligent equipment, the establishment and validation of electronic scales is also an interesting direction.

Expression of NEAT1 can be used as a predictor for Dex resistance in multiple myeloma patients.

OBJECTIVE: Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. METHODS: Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. RESULTS: It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. CONCLUSION: LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM.

Tetrahedral Bonding Structure (Ni3 -Se) Induced by Lattice-Distortion of Ni to Achieve High Catalytic Activity in Na-Se Battery.

Fabrication of transition-metal catalytic materials is regarded as a promising strategy for developing high-performance sodium-selenium (Na-Se) batteries. However, more systematic explorations are further demanded to find out how their bonding interactions and electronic structures can affect the Na storage process. This study finds that lattice-distorted nickel (Ni) structure can form different bonding structures with Na2 Se4 , providing high activity to catalyze the electrochemical reactions in Na-Se batteries. Using this Ni structure to prepare electrode (Se@NiSe2 /Ni/CTs) can realize rapid charge transfer and high cycle stability of the battery. The electrode exhibits high storage performance of Na+ ; i.e., 345 mAh g⁻1 at 1 C after 400 cycles, and 286.4 mAh g⁻1 at 10 C in rate performance test. Further results reveal the existence of a regulated electronic structure with upshifts of the d-band center in the distorted Ni structure. This regulation changes the interaction between Ni and Na2 Se4 to form a Ni3 -Se tetrahedral bonding structure. This bonding structure can provide higher adsorption energy of Ni to Na2 Se4 to facilitate the redox reaction of Na2 Se4 during the electrochemical process. This study can inspire the design of bonding structure with high performance in conversion-reaction-based batteries.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex.

The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Here, we identify PPP2R1A by proteomics as a protein differentially associated with the WAVE complex subunit ABI1 when RAC1 is activated and downstream generation of branched actin is blocked. PPP2R1A is found to associate at the lamellipodial edge with an alternative form of WAVE complex, the WAVE Shell Complex, that contains NHSL1 instead of the Arp2/3 activating subunit WAVE, as in the canonical WAVE Regulatory Complex. PPP2R1A is required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement is abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impair WAVE Shell Complex binding and migration regulation, suggesting that the coupling of PPP2R1A to the WAVE Shell Complex is essential to its function.

The Reliability and Accuracy of the Medial Malleolar Fracture Classification Based on 3D CT Reconstruction.

OBJECTIVE: There is a new medial malleolar fracture classification based on 3D CT reconstruction. However, there is no study assessing the reliability and accuracy of the new classification system and comparison between the new and the classic classification. This study aimed to compare the reliability and accuracy of the medial malleolar fracture classification based on 3D CT reconstruction and the Herscovici classification system. METHODS: We retrospectively analyzed the consecutive ankle fractures in our hospital from January 2013 to September 2020. Five inexperienced and five experienced orthopedic surgeons were included as observers to assess 68 cases with medial malleolar fractures. Ten evaluators classified the cases according to the two classification systems. The reference results of each case were made by the consensus of three senior trauma surgeons. The interobserver reliability, intraobserver reliability, and accuracy were evaluated at an interval of 6 weeks using Fleiss's kappa (κ) statistics. RESULTS: We found substantial interobserver and intraobserver reliability and 81.4% accuracy for the new classification, which was statistically superior to the Herscovici classification (P < 0.05). The reliability and accuracy of both classifications were similar in inexperienced and experienced groups, except for type III in the new classification. The interobserver reliability of type II was the best (P < 0.05), and the intraobserver reliability of IVc ranked the worst (P < 0.05) in the new classification. CONCLUSION: The reliability and accuracy of the new classification are superior to the Herscovici classification. Clinical experiences will not affect the assessment of both classification systems in most instances.

YES-associated protein-regulated Smad7 worsen epithelial barrier injury of chronic sinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES-associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP. METHODS: Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ-binding transcriptional co-activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens-1 (ZO-1), E-cadherin, and transforming growth factor-beta1 (TGF-ß1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO-1, E-cadherin, TGF-ß1, and Smad7 were measured by Western blot. RESULTS: Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF-ß1, ZO-1, and E-cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO-1, E-cadherin, and TGF-ß1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells. CONCLUSIONS: Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF-ß1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress.

Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. The results showed that GLPs consisted of D-glucose, D-galactose, and seven other monosaccharides. The end of the sugar chain had ß-D-Glc and ß-D-Gal configurations. The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the ß-D-Gal configuration, while GLP4 and GLP6 had the ß-D-Glc configuration. The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation.

Intermediate State between MoSe2 and Janus MoSeS during Atomic Substitution Process.

Janus transition metal dichalcogenides (TMDCs), with dissimilar chalcogen atoms on each side of TMDCs, have garnered considerable research attention because of the out-of-plane intrinsic polarization in monolayer TMDCs. Although a plasma process has been proposed for synthesizing Janus TMDCs based on the atomic substitution of surface atoms at room temperature, the formation dynamics and intermediate electronic states have not been completely examined. In this study, we investigated the intermediate state between MoSe2 and Janus MoSeS during plasma processing. Atomic composition analysis and atomic-scale structural observations revealed the intermediate partially substituted Janus (PSJ) structure. Combined with theoretical calculations, we successfully clarified the characteristic Raman modes in the intermediate PSJ structure. The PL exhibited discontinuous transitions that could not be explained by the theoretical calculations. These findings will contribute toward understanding the formation process and electronic-state modulation of Janus TMDCs.