Enhancing Ionic Selectivity and Osmotic Energy by Using an Ultrathin Zr-MOF-Based Heterogeneous Membrane with Trilayered Continuous Porous Structure.

Designing a nanofluidic membrane with high selectivity and fast ion transport property is the key towards high-performance osmotic energy conversion. However, most of reported membranes can produce power density less than commercial benchmark (5 W/m2), due to the imbalance between ion selectivity and permeability. Here, we report a novel nanoarchitectured design of a heterogeneous membrane with an ultrathin and dense zirconium-based UiO-66-NH2 metal-organic framework (MOF) layer and a highly aligned and interconnected branched alumina nanochannel membrane. The design leads to a continuous trilayered pore structure of large geometry gradient in the sequence from angstrom-scale to nano-scale to sub-microscale, which enables the enhanced directional ion transport, and the angstrom-sized (~6.6-7 Å) UiO-66-NH2 windows render the membrane with high ion selectivity. Consequently, the novel heterogeneous membrane can achieve a high-performance power of ~8 W/m2 by mixing synthetic seawater and river water. The power density can be largely upgraded to an ultrahigh ~17.1 W/m2 along with ~48.5% conversion efficiency at a 50-fold KCl gradient. This work not only presents a new membrane design approach but also showcases the great potential of employing the zirconium-based MOF channels as ion-channel-mimetic membranes for highly efficient blue energy harvesting.

Is there a role for routine intraoperative cholangiogram in diagnosing CBD stones in patients with normal liver function tests? A prospective study.

Objectives: Cholecystectomy with or without intraoperative cholangiogram (IOC) is an accepted treatment for cholelithiasis. Up to 11.6 % of cholecystectomies have incidental common bile duct (CBD) stones on IOC and 25.3 % of undiagnosed CBD stones will develop life-threatening complications. These will require additional intervention after primary cholecystectomy, further straining the healthcare system. We seek to examine the role of IOC in patients with normal LFTs by evaluating its predictive values, intending to treat undiagnosed CBD stones and therefore ameliorate these issues. Methods: All patients who underwent cholecystectomies with normal LFTs from October 2019 to December 2020 were prospectively enrolled. IOC was done, ERCPs were performed for filling defects and documented as "true positive" if ERCP was congruent with the IOC. "False positives" were recorded if ERCP was negative. "True negative" was assigned to normal IOC and LFT after 2 weeks of follow-up. Those with abnormal LFTs were subjected to ERCP and documented as "false negative". Sensitivity, specificity, and predictive values were calculated. Results: A total of 180 patients were analysed. IOC showed a specificity of 85.5 % and a NPV of 88.1 % with an AUC of 73.7 %. The positive predictive value and sensitivity were 56.5 and 61.9 % respectively. Conclusions: Routine IOC is a specific diagnostic tool with good negative predictive value. It is useful to exclude the presence of CBD stones when LFT is normal. It does not significantly prolong the length of hospitalization or duration of the cholecystectomy hence reducing the incidence of undetected retained stones and preventing its complications effectively.

Comparison of laparoscopic and open surgery for colorectal malignancy in obese patients: a propensity score-weighted cohort study.

BACKGROUND: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. METHODS: Employing an institutional database from 2009 to 2019, we assessed individuals with a body mass index of ≥30 kg/m2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. We used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. RESULTS: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 mo). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class > III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity-score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. CONCLUSIONS: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.

Female reproductive factors, exogenous hormone use, and incident chronic kidney disease and end-stage renal disease.

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

A new technique for low back pain in lumbar disc herniation: percutaneous endoscopic lumbar discectomy combined with sinuvertebral nerve ablation.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) has demonstrated efficacy in alleviating leg pain among patients with lumbar disc herniation. Nonetheless, residual back pain persists as a troubling issue for surgeons following the procedure. In the treatment of discogenic back pain, sinuvertebral nerve radiofrequency ablation has shown promising results. Nevertheless, the potential benefit of simultaneously implementing sinuvertebral nerve radiofrequency ablation during PELD surgery to address residual back pain has not been thoroughly investigated in current literature. METHODS: This retrospective study reviewed Lumbar disc herniation (LDH) patients with low back pain who underwent combined PELD and sinuvertebral nerve ablation in our department between January 2021 and September 2023. Residual low back pain post-surgery was assessed and compared with existing literature. RESULTS: A total of 80 patients, including 53 males and 27 females, were included in the study. Following surgical intervention, patients demonstrated remarkable improvements in pain and functional parameters. One month post-operatively, the VAS score for low back pain exhibited a 75% reduction (6.45 ± 1.3 to 1.61 ± 1.67), while the VAS score for leg pain decreased by 85% (7.89 ± 1.15 to 1.18 ± 1.26). Notably, the JOA score increased from 12.89 ± 5.48 to 25.35 ± 4.96, and the ODI score decreased form 59.48 ± 9.58 to 20.3 ± 5.37. These improvements were sustained at three months post-operatively. According to the modified Mac Nab criteria, the excellent and good rate was 88.75%. Residual low back pain is observed to be comparatively reduced compared to the findings documented in earlier literature. CONCLUSION: The combination of percutaneous endoscopic lumbar discectomy and sinuvertebral nerve ablation demonstrates effective improvement in low back pain for LDH patients.

Minimizing Contact Resistance and Flicker Noise in Micro Graphene Hall Sensors Using Persistent Carbene Modified Gold Electrodes.

Scalable micro graphene Hall sensors (µGHSs) hold tremendous potential for highly sensitive and label-free biomagnetic sensing in physiological solutions. To enhance the performance of these devices, it is crucial to optimize frequency-dependent flicker noise to reduce the limit of detection (LOD), but it remains a great challenge due to the large contact resistance at the graphene-metal contact. Here we present a surface modification strategy employing persistent carbene on gold electrodes to reduce the contact resistivity by a factor of 25, greatly diminishing µGHS flicker noise by a factor of 1000 to 3.13 × 10-14 V2/Hz while simultaneously lowering the magnetic LOD SB1/2 to 1440 nT/Hz1/2 at 1 kHz under a 100 µA bias current. To the best of our knowledge, this represents the lowest SB1/2 reported for scalable µGHSs fabricated through wafer-scale photolithography. The reduction in contact noise is attributed to the π-π stacking interaction between the graphene and the benzene rings of persistent carbene, as well as the decrease in the work function of gold as confirmed by Kelvin Probe Force Microscopy. By incorporating a microcoil into the µGHS, we have demonstrated the real-time detection of superparamagnetic nanoparticles (SNPs), achieving a remarkable LOD of ∼528 µg/L. This advancement holds great potential for the label-free detection of magnetic biomarkers, e.g., ferritin, for the early diagnosis of diseases associated with iron overload, such as hereditary hemochromatosis (HHC).

Spatial Dissection of the Distinct Cellular Responses to Normal Aging and Alzheimer's Disease in Human Prefrontal Cortex at Single-Nucleus Resolution.

Aging significantly elevates the risk for Alzheimer's disease (AD), contributing to the accumulation of AD pathologies, such as amyloid-ß (Aß), inflammation, and oxidative stress. The human prefrontal cortex (PFC) is highly vulnerable to the impacts of both aging and AD. Unveiling and understanding the molecular alterations in PFC associated with normal aging (NA) and AD is essential for elucidating the mechanisms of AD progression and developing novel therapeutics for this devastating disease. In this study, for the first time, we employed a cutting-edge spatial transcriptome platform, STOmics® SpaTial Enhanced Resolution Omics-sequencing (Stereo-seq), to generate the first comprehensive, subcellular resolution spatial transcriptome atlas of the human PFC from six AD cases at various neuropathological stages and six age, sex, and ethnicity matched controls. Our analyses revealed distinct transcriptional alterations across six neocortex layers, highlighted the AD-associated disruptions in laminar architecture, and identified changes in layer-to-layer interactions as AD progresses. Further, throughout the progression from NA to various stages of AD, we discovered specific genes that were significantly upregulated in neurons experiencing high stress and in nearby non-neuronal cells, compared to cells distant from the source of stress. Notably, the cell-cell interactions between the neurons under the high stress and adjacent glial cells that promote Aß clearance and neuroprotection were diminished in AD in response to stressors compared to NA. Through cell-type specific gene co-expression analysis, we identified three modules in excitatory and inhibitory neurons associated with neuronal protection, protein dephosphorylation, and negative regulation of Aß plaque formation. These modules negatively correlated with AD progression, indicating a reduced capacity for toxic substance clearance in AD subject samples. Moreover, we have discovered a novel transcription factor, ZNF460, that regulates all three modules, establishing it as a potential new therapeutic target for AD. Overall, utilizing the latest spatial transcriptome platform, our study developed the first transcriptome-wide atlas with subcellular resolution for assessing the molecular alterations in the human PFC due to AD. This atlas sheds light on the potential mechanisms underlying the progression from NA to AD.

Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles.

Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.

The quality of bone and paraspinal muscle in the fragility osteoporotic vertebral compression fracture: a comprehensive comparison between different indicators.

PURPOSE: To evaluate the value of five indicators in predicting OVCF through a retrospective case-control study, and explore the internal correlation of different indicators. METHOD: We retrospectively enrolled patients over 50 years of age who had been subjected to surgery for fragility OVCF at China Japan Friendship Hospital from January 2021 to September 2023. Demographic characteristics, T-score based on dual-energy X-ray absorptiometry (DXA), CT-based Hounsfield unit (HU) value, vertebral bone quality (VBQ) score based on magnetic resonance imaging (MRI), relative cross-sectional area (rCSA) and the rate of fat infiltration (FI) of paraspinal muscle were collected. A 1:1 age- and sex-matched, fracture-free control group was established from patients admitted to our hospital for lumbar spinal stenosis or lumbar disk herniation. RESULTS: A total of 78 patients with lumbar fragility OVCF were included. All the five indicators were significantly correlated with the occurrence of OVCFs. Logistic regression analysis showed that average HU value and VBQ score were significantly correlated with OVCF. The area under the curve (AUC) of VBQ score was the largest (0.89). There was a significantly positive correlation between average T-score, average HU value and average total rCSA. VBQ score was significantly positive correlated with FI. CONCLUSION: VBQ score and HU value has good value in predicting of fragility OVCF. In addition to bone mineral density, we should pay more attention to bone quality, including the fatty signal intensity in bone and the FI in paraspinal muscle.

VEGF-FGF Signaling Activates Quiescent CD63+ Liver Stem Cells to Proliferate and Differentiate.

Understanding the liver stem cells (LSCs) holds great promise for new insights into liver diseases and liver regeneration. However, the heterogenicity and plasticity of liver cells have made it controversial. Here, by employing single-cell RNA-sequencing technology, transcriptome features of Krt19+ bile duct lineage cells isolated from Krt19CreERT; Rosa26R-GFP reporter mouse livers are examined. Distinct biliary epithelial cells which include adult LSCs, as well as their downstream hepatocytes and cholangiocytes are identified. Importantly, a novel cell surface LSCs marker, CD63, as well as CD56, which distinguished active and quiescent LSCs are discovered. Cell expansion and bi-potential differentiation in culture demonstrate the stemness ability of CD63+ cells in vitro. Transplantation and lineage tracing of CD63+ cells confirm their contribution to liver cell mass in vivo upon injury. Moreover, CD63+CD56+ cells are proved to be activated LSCs with vigorous proliferation ability. Further studies confirm that CD63+CD56- quiescent LSCs express VEGFR2 and FGFR1, and they can be activated to proliferation and differentiation through combination of growth factors: VEGF-A and bFGF. These findings define an authentic adult liver stem cells compartment, make a further understanding of fate regulation on LSCs, and highlight its contribution to liver during pathophysiologic processes.

[Feeding ecology of Chaeturichthys stigmatias during autumn in Haizhou Bay]. / 海州湾秋季矛尾虾虎鱼的摄食生态.

Research about feeding ecology of fish is important to understand individual behavior and population development, which is also the basic to analyze trophic structure and function of aquatic ecosystems. Chaetrichthys stigmatias is one of the key species in the Haizhou Bay fisheries ecosystem, which has critical ecological niche within the food web. In this study, we collected samples through bottom trawl surveys during the fall of 2018 in the Haizhou Bay, and analyzed the feeding ecology of C. stigmatias based on both stomach content analysis and stable isotope technology. The results showed that the primary diet groups for C. stigmatias were Ophiuroidea and Shrimp, including Ophiothrix marenzelleri, Ophiopholis mirabilis, Ophiura sarsii, Penaeidae, and Alpheus japonicus. The range of δ13C values of C. stigmatias was from -19.39‰ to -15.74‰, with an average value of (-18.07±0.87)‰, which had no significant correlation with body length. The range of δ15N values was from 8.16‰ to 12.86‰, with an average value of (10.14±1.51)‰, which was positively correlated with body length. The trophic level of C. stigmatias showed a positive relationship with body length, with an average value of (3.74±0.34) and a range value of 3.32 to 4.20 among different size groups. The contribution rates of different prey groups varied significantly. Based on the structural equation modeling, we found that the feeding intensity of C. stigmatias was primally influenced by body length, sea bottom salinity, sea bottom temperature, and water depth, with a particularly signi-ficant positive correlation with body length. The combination of stable isotope technology and stomach content analysis methods could contribute to comprehensive understanding on the feeding ecology of C. stigmatias, providing essential data and foundation for research on trophic structures and resource conservation in the Haizhou Bay ecosystem.

Robust Gaussian Process Regression Method for Efficient Tunneling Pathway Optimization: Application to Surface Processes.

Simulation of surface processes is a key part of computational chemistry that offers atomic-scale insights into mechanisms of heterogeneous catalysis, diffusion dynamics, and quantum tunneling phenomena. The most common theoretical approaches involve optimization of reaction pathways, including semiclassical tunneling pathways (called instantons). The computational effort can be demanding, especially for instanton optimizations with an ab initio electronic structure. Recently, machine learning has been applied to accelerate reaction-pathway optimization, showing great potential for a wide range of applications. However, previous methods still suffer from numerical and efficiency issues and were not designed for condensed-phase reactions. We propose an improved framework based on Gaussian process regression for general transformed coordinates, which has improved efficiency and numerical stability, and we propose a descriptor that combines internal and Cartesian coordinates suitable for modeling surface processes. We demonstrate with 11 instanton optimizations in three representative systems that the improved approach makes ab initio instanton optimization significantly cheaper, such that it becomes not much more expensive than a classical transition-state theory rate calculation.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration.

BACKGROUND: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration. RESULTS: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). CONCLUSIONS: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.

A Spectroscopic Method for Distinguishing Two Novel Sandwich-Type Tungsten Oxide Cluster Compounds.

This study introduces two novel sandwich-type tungsten-oxygen cluster compounds synthesized by hydrothermal methods, H4(C6H12N2H2)3{Na(H2O)2[Mn2(H2O)(GeW9O34)]}2 (Compound 1) and H2(C6H12N2H2)3.5{Na3(H2O)4[Co2(H2O)(GeW9O34)]2}·17H2O (Compound 2). The two compounds comprise cluster anions [GeW9O34]10- coordinated with transition metal atoms, either Mn or Co, and are stabilized by organic ligands. These compounds are crystallized in the hexagonal crystal system and P63/m space group. The two compounds were characterized through various techniques. Fourier transform infrared (IR) spectroscopy showed absorption peaks of anionic backbone vibrations of the Keggin cluster at 500-1000 cm-1, IR spectral peaks of δ(N-H) and νas(C-N) of the ligand triethylenediamine at 1000-2000 cm-1, and IR spectral peaks of the ligand νas(N-H) and νas(O-H) of water at 3000-3500 cm-1. Despite similar one-dimensional (1D) IR spectra due to the same cluster anions and similar molecular structures, the two compounds exhibited distinct responses in two-dimensional correlation spectroscopy with IR under magnetic and thermal perturbations. Under magnetic perturbation, Compound 1 showed a strong response peak for νas(W-Ob-W), while Compound 2 exhibited a strong response peak for νas(W=Od), possibly linked to differing magnetic particles. Similarly, Compound 1 displayed a strong response peak under thermal perturbation for νas(W-Oc-W). In contrast, Compound 2 showed a strong response peak for νas(W=Od); these results may be attributed to the different hydrogen bonding connections between the two compounds, which affect the groups in distinct ways through vibration and transmit these vibrations to the W-O bonds. The research presented in this paper expands the theoretical and experimental data of 2D correlation IR spectroscopy.

Paracrinal regulation of neutrophil functions by coronaviral infection in iPSC-derived alveolar type II epithelial cells.

Coronaviruses (CoVs) are enveloped single-stranded RNA viruses that predominantly attack the human respiratory system. In recent decades, several deadly human CoVs, including SARS-CoV, SARS-CoV-2, and MERS-CoV, have brought great impact on public health and economics. However, their high infectivity and the demand for high biosafety level facilities restrict the pathogenesis research of CoV infection. Exacerbated inflammatory cell infiltration is associated with poor prognosis in CoV-associated diseases. In this study, we used human CoV 229E (HCoV-229E), a CoV associated with relatively fewer biohazards, to investigate the pathogenesis of CoV infection and the regulation of neutrophil functions by CoV-infected lung cells. Induced pluripotent stem cell (iPSC)-derived alveolar epithelial type II cells (iAECIIs) exhibiting specific biomarkers and phenotypes were employed as an experimental model for CoV infection. After infection, the detection of dsRNA, S, and N proteins validated the infection of iAECIIs with HCoV-229E. The culture medium conditioned by the infected iAECIIs promoted the migration of neutrophils as well as their adhesion to the infected iAECIIs. Cytokine array revealed the elevated secretion of cytokines associated with chemotaxis and adhesion into the conditioned media from the infected iAECIIs. The importance of IL-8 secretion and ICAM-1 expression for neutrophil migration and adhesion, respectively, was demonstrated by using neutralizing antibodies. Moreover, next-generation sequencing analysis of the transcriptome revealed the upregulation of genes associated with cytokine signaling. To summarize, we established an in vitro model of CoV infection that can be applied for the study of the immune system perturbations during severe coronaviral disease.

Variation in structural motifs within SARS-related coronavirus spike proteins.

SARS-CoV-2 is the third known coronavirus (CoV) that has crossed the animal-human barrier in the last two decades. However, little structural information exists related to the close genetic species within the SARS-related coronaviruses. Here, we present three novel SARS-related CoV spike protein structures solved by single particle cryo-electron microscopy analysis derived from bat (bat SL-CoV WIV1) and civet (cCoV-SZ3, cCoV-007) hosts. We report complex glycan trees that decorate the glycoproteins and density for water molecules which facilitated modeling of the water molecule coordination networks within structurally important regions. We note structural conservation of the fatty acid binding pocket and presence of a linoleic acid molecule which are associated with stabilization of the receptor binding domains in the "down" conformation. Additionally, the N-terminal biliverdin binding pocket is occupied by a density in all the structures. Finally, we analyzed structural differences in a loop of the receptor binding motif between coronaviruses known to infect humans and the animal coronaviruses described in this study, which regulate binding to the human angiotensin converting enzyme 2 receptor. This study offers a structural framework to evaluate the close relatives of SARS-CoV-2, the ability to inform pandemic prevention, and aid in the development of pan-neutralizing treatments.

Clinical, Electrodiagnostic, and Ultrasound Findings in 87 Patients With Finger Drop.

BACKGROUND: The inability to extend the fingers at the metacarpophalangeal and interphalangeal joints leads to finger drop. While wrist drop and foot drop are well recognized, the causes of finger drop are poorly understood. AIMS: This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) features in patients with finger drop. MATERIALS AND METHODS: This is a retrospective study of 87 patients presenting with finger drop and referred for EDX studies during the past 10 years. We analyzed the clinical picture, EDX data, and US findings. The patients were categorized into global (all five digits) or partial (limited to 1-4 digits) finger drop. RESULTS: Fifty-six (64%) patients had global finger drop, while 31 (36%) had partial finger drop. The frequent cause of finger drop was Parsonage-Turner syndrome (PTS) (29 [33%]), followed by trauma (23 [26%]), cervical radiculopathy (16 [18%]), extensor tendon rupture (four [4%]), and compression/entrapment (two [2%]). In 13 (15%) patients, no cause was identified. A total of 13/16 (81%) patients with cervical radiculopathy and four of the patients with tendon rupture had partial finger drop, while 52/64 (81%) with posterior interosseous nerve (PIN) neuropathy had global finger drop. Of the 16 patients who experienced cervical radiculopathy as the cause of the finger drop, 15 patients had C7 and C8 radiculopathy and one patient had C7 radiculopathy. EDX studies of patients with PTS revealed partial axon loss in 18 (62%) patients, conduction block in eight (28%), and total axon loss in four (14%). Enlarged fascicles were observed by US in 40% of patients with PTS. EDX studies of patients who sustained iatrogenic nerve injury causing finger drop demonstrated total axon loss in six (46%) patients, partial axon loss in four (31%), demyelination in two (15%), and conduction block in two (15%). CONCLUSIONS: PIN neuropathy is the most common cause of finger drop, however, lesser-known causes such as cervical radiculopathy and extensor tendon rupture should also be considered. Global finger drop is suggestive of PIN neuropathy, while partial finger drop occurs more often in cervical radiculopathy and tendon rupture. EDX and US studies provide valuable information for localizing the lesion site and may reveal the cause of the finger drop.

F-actin/DRP1 axis-mediated mitochondrial fission promotes mitophagy in diabetic submandibular glands.

BACKGROUND: Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation. MATERIALS AND METHODS: A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed. RESULTS: More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction. CONCLUSIONS: F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway.

BACKGROUND: Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved. Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process. AIM: To assess the influence of interleukin-10 (IL-10) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) following their interaction with macrophages in an inflammatory environment. METHODS: IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment. In this study, we investigated its impact on the proliferation, migration, and osteogenesis of BMSCs. The expression levels of signal transducer and activator of transcription 3 (STAT3) and its activated form, phosphorylated-STAT3, were examined in IL-10-stimulated macrophages. Subsequently, a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling. RESULTS: IL-10-stimulated macrophages underwent polarization to the M2 type through substitution, and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs. Mechanistically, STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages. Specifically, IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response, as evidenced by its diminished impact on the osteogenic differentiation of BMSCs. CONCLUSION: Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs. The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs' osteogenic differentiation.