Generation of a control induced pluripotent stem cell line (SDUCHi001-A) from a healthy male donor.

An induced pluripotent stem cell (iPSC) line (SDUCHi001-A) was established using peripheral blood mononuclear cells (PBMCs) from a healthy 6 years old boy. Reprogramming of the PBMCs was achieved through non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL, and c-MYC. The iPSC line expressed pluripotency markers, had a normal karyotype and trilineage differentiation potential.

Why are graminoid species more dominant? Trait-mediated plant-soil feedbacks shape community composition.

Species traits may determine plant interactions along with soil microbiome, further shaping plant-soil feedbacks (PSFs). However, how plant traits modulate PSFs and, consequently, the dominance of plant functional groups remains unclear. We used a combination of field surveys and a two-phase PSF experiment to investigate whether forbs and graminoids differed in PSFs and in their trait-PSF associations. When grown in forb-conditioned soils, forbs experienced stronger negative feedbacks, while graminoids experienced positive feedbacks. Graminoid-conditioned soil resulted in neutral PSFs for both functional types. Forbs with thin roots and small seeds showed more-negative PSFs than those with thick roots and large seeds. Conversely, graminoids with acquisitive root and leaf traits (i.e., thin roots and thin leaves) demonstrated greater positive PSFs than graminoids with thick roots and tough leaves. By distinguishing overall and soil biota-mediated PSFs, we found that the associations between plant traits and PSFs within both functional groups were mainly mediated by soil biota. A simulation model demonstrated that such differences in PSFs could lead to a dominance of graminoids over forbs in natural plant communities, which might explain why graminoids dominate in grasslands. Our study provides new insights into the differentiation and adaptation of plant life-history strategies under selection pressures imposed by soil biota.

A Novel Method for Obtaining Analytical Parameters Based on Double-Flank Measurement.

Double-flank measurement is the most commonly used method for full inspection of mass-produced gears and has high measurement efficiency, but it cannot obtain the analytical parameters and is not helpful enough to evaluate the NVH performance of the gears. Based on the double-flank rolling tester with a new principle, a simulation method for double-flank measurement and a solving method for analytical parameters are proposed. Using the simulation method, the double-flank measurements without random error can be obtained through the collision detection algorithm. The solving method uses the iteration to obtain the minimum rolling length of each position of the tooth surface, then obtains the analytical parameters of the gear. In the experiments, the difference between the profile deviations obtained by the solving method and superimposed in the simulation method is less than 0.03 µm. The experiment results have verified the correctness of the simulation method and the solving method. These methods can greatly improve the value of double-flank measurement.

Effect of connexin 43 in LPS/IL-4-induced macrophage M1/M2 polarization: An observational study.

Lipopolysaccharide (LPS) and interleukin-4 (IL-4) play important roles in inducing M1 and M2 macrophage polarization. Studies have shown that LPS can promote the polarization of macrophages to M1-type and produce many pro-inflammatory cytokines, while IL-4 can promote the polarization of macrophages to M2-type and produce many anti-inflammatory cytokines. Moreover, Connexin 43 (Cx43) is widely expressed in macrophages and has various regulatory functions. However, whether Cx43 is involved in the regulation of macrophage M1/M2 polarization has not been fully studied. This study examined the role of Cx43 and M2 polarization markers using Western blot, immunofluorescence, flow cytometry. Cx43 overexpression was induced using Cx43 overexpressing lentivirus. The statistical software SPSS 20.0 (IBM Corp.) and GraphPad Prism 8.0 (GraphPad Software, La Jolla, CA, United States) were used to analyze the results. P values < .05 were considered to indicate statistically significant differences. Our results showed that LPS promotes the polarization of macrophages to M1-type, which is accompanied by an increase in Cx43 expression from 0 to 24 hours. Moreover, the application of the Cx43-specific blockers Gap19 and Gap26 reduces the expression of macrophage M1-type polarization markers. Thus, the expression of Cx43 increases first, and then, due to the initiation of intracellular autophagy during LPS-induced macrophage M1 polarization. Cx43 is degraded and the expression of Cx43 decreases from 24 hours to 48 hours. IL-4 decreases the expression of Cx43 from 24 hours to 48 hours and promotes the transformation of macrophages to M2-type. The application of Cx43 overexpression lentivirus leads to a reduction in the expression of M2 polarization markers. IL-4-induced M2 polarization of macrophages inhibits cell autophagy, reducing Cx43 degradation and leading to an increase in Cx43 from 24 hours to 48 hours. Thus, Cx43 expression in M2-type polarization experiences a reduction at first and then an increase from 24 hours to 48 hours. The direction of macrophage polarization can be controlled by regulating the expression of Cx43, thus providing a theoretical basis for treating atherosclerosis, tumors, and other diseases associated with macrophage polarization.

Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area.

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

Chinese surgical robot-assisted surgery for parotid tumor: a case report.

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.

Metabolomic profiles predict clinical severity in patients with obstructive sleep apnea hypopnea syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) poses a significant health hazard, as intermittent hypoxia inflicts damage throughout the body and is considered a critical risk factor for metabolic disorders. The aim of this study was to establish a metabolic profile for patients with OSAHS using nontargeted metabolomics detection techniques, providing a basis for OSAHS diagnosis and novel biological marker identification. METHODS: Forty-five patients with OSAHS composed the OSAHS group, and 44 healthy volunteers composed the control group. Nontargeted metabolomics technology was used to analyze participants' urinary metabolites. Differentially abundant metabolites were screened and correlated through hierarchical clustering analysis. We constructed a composite metabolite diagnostic model using a random forest model. Simultaneously, we analyzed the relationships between 20 metabolites involved in model construction and OSAHS severity. RESULTS: The urinary metabolomics pattern of the OSAHS group exhibited significant changes, demonstrating noticeable differences in metabolic products. Urinary metabolite analysis revealed differences between the mild-moderate OSAHS and severe OSAHS groups. The composite metabolite model constructed in this study demonstrated excellent diagnostic performance not only in distinguishing healthy control participants from patients with mild-moderate OSAHS (AUC = 0.78) and patients with severe OSAHS (AUC = 0.78), but also in discriminating between patients with mild-moderate and severe OSAHS (AUC = 0.71). CONCLUSIONS: This study comprehensively analyzed the urinary metabolomic characteristics of patients with OSAHS. The established composite metabolite model provides robust support for OSAHS diagnosis and severity assessment. Twenty metabolites associated with OSAHS disease severity offer a new perspective for diagnosis.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.

Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis.

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes' viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

Calibration Method Based on Virtual Gear Artefact for Computer Vision Measuring Instrument of Fine Pitch Gear.

The verification of the correctness, adaptability, and robustness of software systems in modern precision measurement instruments is of great significance. Due to the difficulty in processing and calibrating high-precision fine-pitch gear artefacts, the function verification and accuracy calibration of vision measurement instruments for the fine-pitch gear have become a challenge. The calibration method of the gear vision measurement system based on the virtual gear artefact involves two steps, namely obtaining and applying the virtual artefact. The obtained virtual gear artefact has the same geometric features, error features, and image edge features as the real artefact. The calibration method based on the virtual artefact can complete the correctness verification of the gear vision measurement system, and is superior to the traditional methods in adaptability verification, robustness verification, and fault analysis. In a test, the characteristic error of the virtual gear artefact could be reproduced with the original shape in the evaluation results of the computer vision gear measurement (CVGM) system, while the reproduction error did not exceed 1.9 µm. This can meet the requirements of the verification of the gear vision measurement software. The application of the virtual gear artefact can significantly improve the accuracy and robustness of the computer vision measuring instrument of the fine-pitch gear.

Uppermost global tree elevations are primarily limited by low temperature or insufficient moisture.

The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi-observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing-season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two-thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.

Changes in microbial composition explain the contrasting responses of glucose and lignin decomposition to soil acidification in an alpine grassland.

Soil acidification often suppresses microbial growth and activities, resulting in a negative impact on soil organic carbon (C) decomposition. While the detrimental effects of acidification on soil and plant properties have been extensively studied, less attention has been paid on the shifts in soil microbial communities and their influences of the decomposition of organic C with different chemical complexities. Taking advantage of an acid addition experiment in a Tibetan alpine meadow, here we examined the response of soil microbial communities to soil acidification and microbial effect on the decomposition of organic C with different chemical complexities (i.e., glucose and lignin, representing labile and recalcitrant C respectively). We found that soil acidification had no impact on microbial respiration and microbial abundance even though it decreased bacterial diversity significantly. Soil acidification increased the relative abundance of some microbial taxa, like Alphaproteobacteria and Acidobacteriia in bacteria increased by 36 %, 284 %, and Eurotiomycetes, Sordariomycetes and Leotiomycetes in fungi increased by 145 %, 279 % and 12.7-fold, but decreased the relative abundance of Acidimicrobiia by 33 % in highest acid addition treatment. Changes in microbial communities (bacterial and fungal community composition, the diversity of bacterial community and the ratio of fungi to bacteria) are significantly related to the decomposition of glucose and lignin. More specifically, soil acidification decreased the decomposition of glucose but increased the decomposition of lignin, indicating a trade-off between the decomposition of labile and recalcitrant soil organic C under soil acidification. Overall, shifts in microbial communities under soil acidification might be accompanied by an increased ability to break down more recalcitrant C. This trade-off between the decomposition of labile and recalcitrant C may change soil C quality under future acid deposition scenarios.

Urban-Rural Disparities in the Association Between Home- and Community-Based Service Utilization and Levels of Disability Among Chinese Older Adults With Disabilities.

Home- and community-based services (HCBS) are optimal ways to deal with disability problems among older adults. This study aims to analyze urban-rural disparities in the relationship between HCBS utilization and levels of disability among Chinese older adults with disabilities, so as to meet the long-term care needs of them. In applying the Andersen Behavioral Model, bivariate analysis and multivariate regression models were employed using data from 843 older adults with disabilities from the 2018 China Longitudinal Aging Social Survey (CLASS). After adjusting covariates, disability levels among Chinese older adults with disabilities were significantly correlated with HCBS utilization in urban areas but not in rural areas. The urban-rural disparities may be due to the low utilization of HCBS in rural areas (only 11.2%) among older adults with disabilities compared with their urban counterparts (22.7%).

Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion.

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.

Control of breathing by orexinergic signaling in the nucleus tractus solitarii.

Orexin signaling plays a facilitatory role in respiration. Abnormalities in orexin levels correlate with disordered breathing patterns and impaired central respiratory chemoreception. Nucleus tractus solitarii (NTS) neurons expressing the transcription factor Phox2b contribute to the chemoreceptive regulation of respiration. However, the extent to which orexinergic signaling modulates respiratory activity in these Phox2b-expressing NTS neurons remains unclear. In the present study, the injection of orexin A into the NTS significantly increased the firing rate of the phrenic nerve. Further analysis using fluorescence in situ hybridization and immunohistochemistry revealed that orexin 1 receptors (OX1Rs) were primarily located in the ventrolateral subdivision of the NTS and expressed in 25% of Phox2b-expressing neurons. Additionally, electrophysiological recordings showed that exposure to orexin A increased the spontaneous firing rate of Phox2b-expressing neurons. Immunostaining experiments with cFos revealed that the OX1R-residing Phox2b-expressing neurons were activated by an 8% CO2 stimulus. Crucially, OX1R knockdown in these NTS neurons notably blunted the ventilatory response to 8% CO2, alongside an increase in sigh-related apneas. In conclusion, orexinergic signaling in the NTS facilitates breathing through the activation of OX1Rs, which induces the depolarization of Phox2b-expressing neurons. OX1Rs are essential for the involvement of Phox2b-expressing NTS neurons in the hypercapnic ventilatory response.

Surface modifications towards superhydrophobic wood-based composites: Construction strategies, functionalization, and perspectives.

Amidst the burgeoning interest in multifunctional superhydrophobic wood-based composites (SWBCs) for their varied applications and the need for improved environmental resilience, recent efforts focus on enhancing their utility by integrating features such as mechanical and chemical stability, self-healing capabilities, flame resistance, and antimicrobial properties. Research indicates that various external conditions can influence the wettability and additional characteristics of SWBCs. This comprehensive review outlines three critical factors affecting SWBCs' performance: synthesis methods, wood taxonomy, and chemical agents. It further provides a detailed overview of SWBCs' specific attributes, including essential qualities for diverse applications and the limitations posed by different contexts. Additionally, it elaborates on performance evaluation techniques, offering a foundational framework for SWBCs' practical application. This work aims to serve as an important resource for future research and development in SWBC engineering.

Targeted Delivery of Catalase and Photosensitizer Ce6 by a Tumor-Specific Aptamer Is Effective against Bladder Cancer In Vivo.

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

CRF regulates pain sensation by enhancement of corticoaccumbal excitatory synaptic transmission.

Both peripheral and central corticotropin-releasing factor (CRF) systems have been implicated in regulating pain sensation. However, compared with the peripheral, the mechanisms underlying central CRF system in pain modulation have not yet been elucidated, especially at the neural circuit level. The corticoaccumbal circuit, a structure rich in CRF receptors and CRF-positive neurons, plays an important role in behavioral responses to stressors including nociceptive stimuli. The present study was designed to investigate whether and how CRF signaling in this circuit regulated pain sensation under physiological and pathological pain conditions. Our studies employed the viral tracing and circuit-, and cell-specific electrophysiological methods to label the CRF-containing circuit from the medial prefrontal cortex to the nucleus accumbens shell (mPFCCRF-NAcS) and record its neuronal propriety. Combining optogenetic and chemogenetic manipulation, neuropharmacological methods, and behavioral tests, we were able to precisely manipulate this circuit and depict its role in regulation of pain sensation. The current study found that the CRF signaling in the NAc shell (NAcS), but not NAc core, was necessary and sufficient for the regulation of pain sensation under physiological and pathological pain conditions. This process was involved in the CRF-mediated enhancement of excitatory synaptic transmission in the NAcS. Furthermore, we demonstrated that the mPFCCRF neurons monosynaptically connected with the NAcS neurons. Chronic pain increased the protein level of CRF in NAcS, and then maintained the persistent NAcS neuronal hyperactivity through enhancement of this monosynaptic excitatory connection, and thus sustained chronic pain behavior. These findings reveal a novel cell- and circuit-based mechanistic link between chronic pain and the mPFCCRF → NAcS circuit and provide a potential new therapeutic target for chronic pain.