Effects of Capsular Polysaccharide amount on Pneumococcal-Host interactions.

Among the many oral streptococci, Streptococcus pneumoniae (Spn) stands out for the capacity of encapsulated strains to cause invasive infection. Spread beyond upper airways, however, is a biological dead end for the organism, raising the question of the benefits of expending energy to coat its surface in a thick layer of capsular polysaccharide (CPS). In this study, we compare mutants of two serotypes expressing different amounts of CPS and test these in murine models of colonization, invasion infection and transmission. Our analysis of the effect of CPS amount shows that Spn expresses a capsule of sufficient thickness to shield its surface from the deposition of complement and binding of antibody to underlying epitopes. While effective shielding is permissive for invasive infection, its primary contribution to the organism appears to be in the dynamics of colonization. A thicker capsule increases bacterial retention in the nasopharynx, the first event in colonization, and also impedes IL-17-dependent clearance during late colonization. Enhanced colonization is associated with increased opportunity for host-to-host transmission. Additionally, we document substantial differences in CPS amount among clinical isolates of three common serotypes. Together, our findings show that CPS amount is highly variable among Spn and could be an independent determinant affecting host interactions.

MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model.

Acute lung injury (ALI) is an inflammatory disease associated with alveolar injury, subsequent macrophage activation, inflammatory cell infiltration, and cytokine production. Mesenchymal stem cells (MSCs) are beneficial for application in the treatment of inflammatory diseases due to their immunomodulatory effects. However, the mechanisms of regulatory effects by MSCs on macrophages in ALI need more in-depth study. Lung tissues were collected from mice for mouse lung organoid construction. Alveolar macrophages (AMs) derived from bronchoalveolar lavage and interstitial macrophages (IMs) derived from lung tissue were co-cultured, with novel matrigel-spreading lung organoids to construct an in vitro model of lung organoids-immune cells. Mouse compact bone-derived MSCs were co-cultured with organoids-macrophages to confirm their therapeutic effect on acute lung injury. Changes in transcriptome expression profile were analyzed by RNA sequencing. Well-established lung organoids expressed various lung cell type-specific markers. Lung organoids grown on spreading matrigel had the property of functional cells growing outside the lumen. Lipopolysaccharide (LPS)-induced injury promoted macrophage chemotaxis toward lung organoids and enhanced the expression of inflammation-associated genes in inflammation-injured lung organoids-macrophages compared with controls. Treatment with MSCs inhibited the injury progress and reduced the levels of inflammatory components. Furthermore, through the nuclear factor-κB pathway, MSC treatment inhibited inflammatory and phenotypic transformation of AMs and modulated the antigen-presenting function of IMs, thereby affecting the inflammatory phenotype of lung organoids. Lung organoids grown by spreading matrigel facilitate the reception of external stimuli and the construction of in vitro models containing immune cells, which is a potential novel model for disease research. MSCs exert protective effects against lung injury by regulating different functions of AMs and IMs in the lung, indicating a potential mechanism for therapeutic intervention.

Copper-Catalyzed Diastereo-, Enantio-, and (Z)-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols.

We introduce a method for the (Z)-selective aminoallylation of a range of ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo- and enantioselectivity. Copper-catalyzed reductive couplings of 2-azatrienes with aryl/alkyl and dialkyl ketones proceed with Ph-BPE as the supporting ligand, generating anti-amino alcohols with >98% (Z)-selectivity under mild conditions. The utility of the products is highlighted through several transformations, including those that leverage the (Z)-allylic amine moiety for diastereoselective reactions of the alkene. Calculations illustrate Curtin-Hammett control in the product formation over other possible isomers and the origin of (Z)-selectivity.

Diamond-Reinforced Al(H2PO4)3@Epoxy Hybrid Thermal Adhesive With Ultra-High Thermal Conductivity and Bonding Strength.

The miniaturization, integration, and increased power of electronic devices have exacerbated serious heat dissipation issues. Thermally conductive adhesives, which effectively transfer heat and firmly bond components, are critical for addressing these challenges. This paper innovatively proposed a composite comprising inorganic phosphate/alumina as a matrix and diamond as filler. The composite achieved an isotropic thermal conductivity (TC) of up to 18.96 W m-1 K-1, significantly surpassing existing reports while maintaining electrical insulation. First-principles calculations and experimental tests confirmed that the high TC of phosphate and excellent interface contact ensured efficient heat transfer. To optimize bonding performance, a modified-diamond/Al(H2PO4)3@epoxy hybrid composite is subsequently developed using an organic modification method. The unique hybrid structure, combining inorganic thermal pathways and an organic adhesive network, enabled the hybrid composite to simultaneously possess a high TC (3.23 W m-1 K-1) and strong adhesion (14.35 MPa). Compared to previous reports, the comprehensive performance of this hybrid thermally conductive adhesive is exceptionally remarkable. The superior heat dissipation capability of the hybrid thermal adhesive is demonstrated in chip cooling scenarios. This organic/inorganic hybrid approach offered a new direction for obtaining advanced thermal interface materials, demonstrating significant application potential in chip soldering, packaging, and heat dissipation.

Ultrafast-Loaded Nickel Sulfide on Vertical Graphene Enabled by Joule Heating for Enhanced Lithium Metal Batteries.

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

Identification of New Compounds against PRRSV Infection by Directly Targeting CD163.

The porcine reproductive and respiratory syndrome viruses (PRRSV) led to a global panzootic and huge economical losses to the pork industry. PRRSV targets the scavenger receptor CD163 for productive infection. However, currently no effective treatment is available to control the spread of this disease. Using bimolecular fluorescence complementation (BiFC) assays, we screened a set of small molecules potentially targeting the scavenger receptor cysteine-rich domain 5 (SRCR5) of CD163. We found that the assay examining protein-protein interactions (PPI) between PRRSV glycoprotein 4 (GP4) and the CD163-SRCR5 domain mainly identifies compounds that potently inhibit PRRSV infection, while examining the PPI between PRRSV-GP2a and the SRCR5 domain maximized the identification of positive compounds, including additional ones with various antiviral capabilities. These positive compounds significantly inhibited both types 1 and 2 PRRSV infection of porcine alveolar macrophages. We confirmed that the highly active compounds physically bind to the CD163-SRCR5 protein, with dissociation constant (KD) values ranging from 28 to 39 µM. Structure-activity-relationship (SAR) analysis revealed that although both the 3-(morpholinosulfonyl)anilino and benzenesulfonamide moieties in these compounds are critical for the potency to inhibit PRRSV infection, the morpholinosulfonyl group can be replaced by chlorine substituents without significant loss of antiviral potency. Our study established a system for throughput screening of natural or synthetic compounds highly effective on blocking of PRRSV infection and shed light on further SAR modification of these compounds. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the swine industry worldwide. Current vaccines cannot provide cross protection against different strains, and there are no effective treatments available to hamper the spread of this disease. In this study, we identified a group of new small molecules that can inhibit the PRRSV interaction with its specific receptor CD163 and dramatically block the infection of both types 1 and type 2 PRRSVs to host cells. We also demonstrated the physical association of these compounds with the SRCR5 domain of CD163. In addition, molecular docking and structure-activity relationship analyses provided new insights for the CD163/PRRSV glycoprotein interaction and further improvement of these compounds against PRRSV infection.

Rapid in-situ calibration of computational micro-spectrometer with few-shot meta-learning.

Computational micro-spectrometers comprised of detector arrays and encoding structure arrays, such as on-chip Fabry-Perot (FP) cavity filters, have great potential in many in-situ applications owing to their compact size and snapshot imaging ability. Given manufacturing deviation and environmental influence are inevitable, easy and effective calibration for spectrometer is necessary, especially for in-situ applications. Currently calibration strategies based on iterative algorithms or neural networks require accurate measurements of pixel-level (spectral) encoding functions through monochromator or large amounts of standard samples. These procedures are time-consuming and expensive, thereby impeding in-situ applications. Meta-learning algorithms with few-shot learning ability can address this challenge by incorporating the prior knowledge in the simulated dataset. In this work, we propose a meta-learning algorithm free of measuring encoding function or large amounts of standard samples to calibrate a micro-spectrometer with manufacturing deviation effectively. Our micro-spectrometer comprises 16 types of FP filters covering a wavelength range of 550-720 nm. The center wavelength of each filter type deviates from the design up to 6 nm. After calibration with 15 different color data, the average reconstruction error on the test dataset decreased from 7.2 × 10-3 to 1.2 × 10-3, and further decreased to 9.4 × 10-4 when the calibration data increased to 24. The performance is comparable to algorithms trained with measured encoding function both in reconstruction error and generalization ability. We estimated that the cost of in-situ calibration through reflectance measurements of color chart decreased to one percent of the cost through monochromator measurements. By exploiting prior deviation information in simulation data with meta-learning, the efficiency and cost of calibration are significantly improved, thereby facilitating the large-scale production and in-situ application of micro-spectrometers.

Integrative analysis of aging-related genes reveals CEBPA as a novel therapeutic target in non-small cell lung cancer.

BACKGROUND: To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. METHODS: Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. RESULTS: Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. CONCLUSIONS: The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.

Auto-hematopoietic stem cell transplantation or chemotherapy? Meta-analysis of clinical choice for AML.

For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41-0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02-1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28-6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85-1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis.

Penicilloneines A and B, Quinolone-Citrinin Hybrids from a Starfish-Derived Penicillium sp.

Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 µg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.

Georg Schmorl Prize of the German Spine Society (DWG) 2023: the influence of sarcopenia and paraspinal muscle composition on patient-reported outcomes: a prospective investigation of lumbar spinal fusion patients with 12-month follow-up.

PURPOSE: This study aimed to investigate the impact of sarcopenia and lumbar paraspinal muscle composition (PMC) on patient-reported outcomes (PROs) after lumbar fusion surgery with 12-month follow-up (12 M-FU). METHODS: A prospective investigation of patients undergoing elective lumbar fusion was conducted. Preoperative MRI-based evaluation of the cross-sectional area (CSA), the functional CSA (fCSA), and the fat infiltration(FI) of the posterior paraspinal muscles (PPM) and the psoas muscle at level L3 was performed. Sarcopenia was defined by the psoas muscle index (PMI) at L3 (CSAPsoas [cm2]/(patients' height [m])2). PROs included Oswestry Disability Index (ODI), 12-item Short Form Healthy Survey with Physical (PCS-12) and Mental Component Scores (MCS-12) and Numerical Rating Scale back and leg (NRS-L) pain before surgery and 12 months postoperatively. Univariate and multivariable regression determined associations among sarcopenia, PMC and PROs. RESULTS: 135 patients (52.6% female, 62.1 years, BMI 29.1 kg/m2) were analyzed. The univariate analysis demonstrated that a higher FI (PPM) was associated with worse ODI outcomes at 12 M-FU in males. Sarcopenia (PMI) and higher FI (PPM) were associated with worse ODI and MCS-12 at 12 M-FU in females. Sarcopenia and higher FI of the PPM are associated with worse PCS-12 and more leg pain in females. In the multivariable analysis, a higher preoperative FI of the PPM (ß = 0.442; p = 0.012) and lower FI of the psoas (ß = -0.439; p = 0.029) were associated with a worse ODI at 12 M-FU after adjusting for covariates. CONCLUSIONS: Preoperative FI of the psoas and the PPM are associated with worse ODI outcomes one year after lumbar fusion. Sarcopenia is associated with worse ODI, PCS-12 and NRS-L in females, but not males. Considering sex differences, PMI and FI of the PPM might be used to counsel patients on their expectations for health-related quality of life after lumbar fusion.

Association between lumbar intervertebral vacuum phenomenon severity and posterior paraspinal muscle atrophy in patients undergoing spine surgery.

PURPOSE: Intervertebral vacuum phenomenon (IVP) and paraspinal muscular atrophy are age-related changes in the lumbar spine. The relationship between both parameters has not been investigated. We aimed to analyze the correlation between IVP and paraspinal muscular atrophy in addition to describing the lumbar vacuum severity (LVS) scale, a new parameter to estimate lumbar degeneration. METHODS: We analyzed patients undergoing spine surgery between 2014 and 2016. IVP severity was assessed utilizing CT scans. The combination of vacuum severity on each lumbar level was used to define the LVS scale, which was classified into mild, moderate and severe. MRIs were used to evaluate paraspinal muscular fatty infiltration of the multifidus and erector spinae. The association of fatty infiltration with the severity of IVP at each lumbar level was assessed with a univariable and multivariable ordinal regression model. RESULTS: Two hundred and sixty-seven patients were included in our study (128 females and 139 males) with a mean age of 62.6 years (55.1-71.2). Multivariate analysis adjusted for age, BMI and sex showed positive correlations between LVS-scale severity and fatty infiltration in the multifidus and erector spinae, whereas no correlation was observed in the psoas muscle. CONCLUSION: IVP severity is positively correlated with paraspinal muscular fatty infiltration. This correlation was stronger for the multifidus than the erector spinae. No correlations were observed in the psoas muscle. The lumbar vacuum severity scale was significantly correlated with advanced disc degeneration with vacuum phenomenon.

Abdominal aortic calcification is an independent predictor of perioperative blood loss in posterior spinal fusion surgery.

OBJECTIVE: Abdominal aortic calcification (AAC), often found incidentally on lateral lumbar radiographs, is increasingly recognized for its association with adverse outcomes in spine surgery. As a marker of advanced atherosclerosis affecting cardiovascular dynamics, this study evaluates AAC's impact on perioperative blood loss in posterior spinal fusion (PSF). METHODS: Patients undergoing PSF from March 2016 to July 2023 were included. Estimated blood loss (EBL) and total blood volume (TBV) were calculated. AAC was assessed on lateral lumbar radiographs according to the Kauppila classification. Predictors of the EBL-to-TBV ratio (%EBL/TBV) were examined via univariable and multivariable regression analyses, which adjusted for parameters such as hypertension and aspirin use. RESULTS: A total of 199 patients (47.2% female) were analyzed. AAC was present in 106 patients (53.3%). AAC independently predicted %EBL/TBV, accounting for an increase in blood loss of 4.46% of TBV (95% CI 1.17-7.74, p = 0.008). CONCLUSIONS: This is the first study to identify AAC as an independent predictor of perioperative blood loss in PSF. In addition to its link to degenerative spinal conditions and adverse postoperative outcomes, the relationship between AAC and increased blood loss warrants attention in patients undergoing PSF.

The Association between prior arthroplasty and Paraspinal Muscle Degeneration in patients undergoing elective lumbar surgery.

PURPOSE: Spinal and lower extremity degeneration often causes pain and disability. Lower extremity osteoarthritis, eventually leading to total knee- (TKA) and -hip arthroplasty (THA), can alter posture through compensatory mechanisms, potentially causing spinal misalignment and paraspinal muscle (PM) atrophy. This study aims to evaluate the association between prior THA or TKA and PM-degeneration in patients undergoing elective lumbar surgery for degenerative conditions. METHODS: A retrospective analysis of patients undergoing lumbar surgery for degenerative conditions was conducted. Patients were categorized based on prior THA, TKA, or both. Quantitative analysis of functional cross-sectional area (fCSA) and fat infiltration (FI) of psoas, multifidus (MF), and erector spinae (ES) muscles at L4-level was performed using T2-weighted MRI images. The association between the FI and fCSA of the PM and prior arthroplasty was investigated. Differences were assessed using ANOVA and multivariable linear regression. RESULTS: Overall, 584 patients (60% female, 64 ± 12 years) were included. 66 patients (11%) had prior TKA, 36 patients (6%) THA, and 15 patients (3%) both TKA and THA. Patients with arthroplasty were mostly female (57%) and notably older (p < 0.001). The FI of the MF and the ES was significantly higher in the arthroplasty-group (both p < 0.001). Patients with prior TKA showed significantly higher FI (Est = 4.3%, p = 0.013) and lower fCSA (Est=-0.9 cm2, p = 0.012) in the MF compared to the non-arthroplasty-group. CONCLUSION: This study demonstrates a significant lower fCSA and higher FI in the MF among individuals with prior TKA. This highlights the complex knee-spine relationship and how these structures interact with each other.

Association between skin ultrasound parameters and revision surgery after posterior spinal fusion.

PURPOSE: The literature is scarce in exploring the role of imaging parameters like ultrasound (US) as a biomarker for surgical outcomes. The purpose of this study is to investigate the associations between skin US parameters and revision surgery following spine lumbar fusion. METHODS: Posterior lumbar fusion patients with 2-years follow-up were assessed. Previous fusion or revision not due to adjacent segment disease (ASD) were excluded. Revisions were classified as cases and non-revision were classified as controls. US measurements conducted at two standardized locations on the lumbar back. Skin echogenicity of the average dermal (AD), upper 1/3 of the dermal (UD), lower 1/3 of the dermal (LD), and subcutaneous layer were measured. Echogenicity was calculated with the embedded echogenicity function of our institution's imaging platform (PACS). Statistical significance was set at p < 0.05. RESULTS: A total of 128 patients (51% female, age 62 [54-72] years) were included in the final analysis. 17 patients required revision surgery. AD, UD, and LD echogenicity showed significantly higher results among revision cases 124.5 [IQR = 115.75,131.63], 128.5 [IQR = 125,131.63] and 125.5 [IQR = 107.91,136.50] compared to the control group 114.3 [IQR = 98.83,124.8], 118.5 [IQR = 109.28,127.50], 114 [IQR = 94.20,126.75] respectively. CONCLUSION: The findings of this study demonstrate a significant association between higher echogenicity values in different layers of the dermis and requiring revision surgery. The results provide insights into the potential use of skin US parameters as predictors for revision surgery. These findings may reflect underlying alterations in collagen. Further research is warranted to elucidate the mechanisms driving these associations.

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

INTRODUCTION: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. MATERIALS AND METHODS: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. RESULTS: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (ß = 0.923;p = 0.031). CONCLUSION: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Fat mass and obesity-associated protein (FTO) affects midpalatal suture bone remodeling during rapid maxillary expansion.

BACKGROUND: The fat mass and obesity-associated protein (FTO) is an RNA demethylase that contributes to several physiological processes. Nonetheless, the impact of FTO on bone remodeling in the midpalatal suture while undergoing rapid maxillary expansion (RME) remains unclear. METHODS: First, to explore the expression of FTO in the midpalatal suture during RME, six rats were randomly divided into two groups: Expansion group and Sham group (springs without being activated). Then, suture mesenchymal stem cells (SuSCs) were isolated as in vitro model. The expression of FTO was knocked down by small interfering RNA to study the effect of FTO on the osteogenic differentiation of SuSCs. Finally, to evaluate the function of FTO in the process of bone remodeling in the midpalatal suture, ten rats were randomly divided into two groups: FB23-2 group (10 µM, a small molecule inhibitor of FTO) and DMSO group (control). RESULTS: Increased arch width and higher expression of OCN and FTO in the midpalatal area were observed in expansion group (P < .05). In the in vitro model, the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b were decreased (P < .05) upon knocking down FTO. Additionally, the protein levels of RUNX2 and OPN were also decreased (P < 0.05). Adding FB23-2, a small-molecule inhibitor targeting FTO, to the medium of SuSCs caused a decrease in the mRNA expression levels of Runx2, Bmp2, Col1a1, Spp1, and Tnfrsf11b (P < 0.05). There was a statistically significant difference in evaluating the expression of OCN and OPN on the palatal suture between the FB23-2 and DMSO groups (P < .05). LIMITATION: The molecular mechanisms by which FTO regulates SuSCs osteogenesis remain to be elucidated. The FTO conditional knock out mouse model can be established to further elucidate the role of FTO during RME. CONCLUSION: FTO contributes to the osteogenic differentiation of SuSCs and plays a promoting role in midpalatal suture bone remodeling during the RME.

Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics. RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate. CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.

Splashing-Assisted Femtosecond Laser-Activated Metal Deposition for Mold- and Mask-Free Fabrication of Robust Microstructured Electrodes for Flexible Pressure Sensors.

Flexible pressure sensors play an indispensable role in flexible electronics. Microstructures on flexible electrodes have been proven to be effective in improving the sensitivity of pressure sensors. However, it remains a challenge to develop such microstructured flexible electrodes in a convenient way. Inspired by splashed particles from laser processing, herein, a method for customizing microstructured flexible electrodes by femtosecond laser-activated metal deposition is proposed. It takes advantage of the catalyzing particles scattered during femtosecond laser ablation and is particularly suitable for moldless, maskless, and low-cost fabrication of microstructured metal layers on polydimethylsiloxane (PDMS). Robust bonding at the PDMS/Cu interface is evidenced by the scotch tape test and the duration test over 10 000 bending cycles. Benefiting from the firm interface, the developed flexible capacitive pressure sensor with microstructured electrodes presents several conspicuous features, including a sensitivity (0.22 kPa-1 ) 73 times higher than the one using flat Cu electrodes, ultralow detection limit (<1 Pa), rapid response/recovery time (4.2/5.3 ms), and excellent stability. Moreover, the proposed method, inheriting the merits of laser direct writing, is capable of fabricating a pressure sensor array in a maskless manner for spatial pressure mapping.

General-purpose mid-infrared micro-spectrometer based on hierarchical residual CNN and data augmentation.

Taking advantage of broad response range and snap-shot operation mode, reconstructive spectrometers based on integrated frequency-modulation microstructure and computational techniques attract lots of attention. The key problems in reconstruction are sparse samplings related with the limited detectors and generalization ability due to data-driving principle. Here, we demonstrate abstractly a mid-infrared micro-spectrometer covering 2.5-5 µm, which utilizes a grating-integrated lead selenide detector array for sampling and a hierarchal residual convolutional neural network (HRCNN) for reconstructions. Leveraging data augmentation and the powerful feature extraction ability of HRCNN, a spectral resolution of 15 nm is realized. Over one hundred chemicals, including untrained chemicals species tested with an average reconstruction error of ∼1E-4, exhibit the excellent reliability of the micro-spectrometer. The demonstration of the micro-spectrometer promotes the development of the reconstructed strategy.