Photocatalytic PPh3-Mediated Synthesis of C3-Functionalized Indoles via Radical Annulation of Nitroarenes and Alkenes.

Oxidatively generated phosphine radical cations are reactive intermediates that can be used for the generation of carbon and heteroatom centered radicals via deoxygenation processes. Such P-radical cations can readily be generated via single electron transfer oxidation using a redox catalyst. Cheap and commercially available nitroarenes are ideal nitrogen sources for the construction of organic amines and N-containing heterocycles. Activation of nitroarenes with phosphines has been achieved in the ionic mode, which requires specially designed P-nucleophiles and high temperatures. Herein, we report an alternative mode of nitro activation that proceeds via a radical process. The radical strategy leads to open shell intermediates that show interesting unexplored reactivity. This is documented by the development of an economic and highly efficient synthesis of valuable indole derivatives through photocatalytic PPh3-mediated annulation of nitroarenes with alkenes showing large functional group tolerance. The method allows room-temperature activation of nitroarenes and a double C-H bond functionalization of alkenes is achieved to provide rapid access to C3-functionalized indoles, which are key structural components of diverse natural and drug molecules. Experimental mechanistic studies that are further supported by DFT calculations indicate that a nitrosoarene radical cation plays a key role in the annulation process.

Dexmedetomidine Alleviates Myocardial Injury Induced by Acute Kidney Injury in Diabetes Mellitus Rats via Regulating the Inflammatory Response.

OBJECTIVE: To study the effect of dexmedetomidine (Dex) on myocardial injury induced by acute kidney injury (AKI) in diabetes mellitus rats and explore the potential mechanisms. METHODS: The Type 2 diabetes mellitus (T2DM) model was prepared in 40 adult male Wistar rats. These rats were randomly divided into four groups (n=10/group), including the control (Con) group, AKI group, Dex preconditioning (DPreC) group, and resveratrol (Res) combined with Dex preconditioning (Res+DPreC) group. The AKI model was prepared in the AKI, DPreC, and Res+DPreC group. The DPreC group received Dex, while the Con and AKI group received normal saline. The Res+DPreC group received Res in addition to Dex preconditioning. Histopathologic, apoptotic, enzymatic, and inflammatory changes in myocardial tissue were observed or detected. RESULTS: Histopathologic, apoptotic, and enzymatic changes in myocardial tissue demonstrated that AKI induced myocardial injury in T2DM rats; Dex preconditioning could mitigate this injury; and RES enhanced this effect. Inflammatory changes suggested that Dex alleviated the inflammatory response induced by AKI in T2DM rats via regulating the expressions of SIRT1, TNF-α, IL-17A, and IL-10. CONCLUSIONS: Dex could alleviate myocardial injury induced by AKI in DM rats via regulating the inflammatory response associated with SIRT1, TNF-α, IL-17A, and IL-10, and Res could enhance this protective effect.

Association between base excess and mortality in critically ill patients with ischemic stroke: a retrospective cohort study.

BACKGROUND: Base excess (BE) is associated with mortality from many diseases. However, the relationship between BE and mortality in patients with ischemic stroke remains uncertain. Our aim is to investigate the relationship between BE values upon admission to the ICU and mortality rates in critically ill stroke patients. METHODS: The current study enrolled 1,572 patients with ischemic stroke (863 males and 709 females). The associations of BE with intensive care unit (ICU), hospital, 28-day, and 1-year mortalities were assessed using multivariable logistic regression or Cox proportional hazards model. The potential impact of the Sequential Organ Failure Assessment (SOFA) score (< 5 or ≥ 5) on the prognostic value of BE was further evaluated with interaction and subgroup analyses. RESULTS: BE values less than - 3 mmol/L, greater than 3 mmol/L, and within - 3 to 3 mmol/L (normal BE) were observed in 316 (20.1%), 175 (11.1%), and 1,081 (68.8%) patients, respectively. The restricted cubic splines analyses revealed that a U-shaped curve between BE and the mortality risk. Multivariable analysis indicated that patients with low BE (<-3 mmol/L) had higher rates of ICU mortality (odds ratio [OR], 1.829; 95% confidence interval [CI], 1.281-2.612; P = 0.001), hospital mortality (OR, 1.484; 95% CI, 1.077-2.045; P = 0.016), 28-day mortality (hazard ratio [HR], 1.522; 95% CI, 1.200-1.929; P = 0.001), and 1-year mortality (HR, 1.399; 95% CI, 1.148-1.705; P = 0.001) than patients with normal BE. Subgroup analyses showed consistent results pertaining to SOFA scores ≥ 5. CONCLUSIONS: In critically ill patients with ischemic stroke, an initial BE of <-3 mmol/L at ICU admission may indicate an increased risk of ICU, hospital, 28-day, and 1-year mortalities.

Hormetic responses to cadmium exposure in wheat seedlings: insights into morphological, physiological, and biochemical adaptations.

Cadmium is commonly recognized as toxic to plant growth, low-level Cd has promoting effects on growth performance, which is so-called hormesis. Although Cd toxicity in wheat has been widely investigated, knowledge of growth response to a broad range of Cd concentrations, especially extremely low concentrations, is still unknown. In this study, the morphological, physiological, and biochemical performance of wheat seedlings to a wide range of Cd concentrations (0-100 µΜ) were explored. Low Cd treatment (0.1-0.5 µM) improved wheat biomass and root development by enhancing the photosynthetic system and antioxidant system ability. Photosynthetic rate (Pn) was improved by 5.72% under lower Cd treatment (1 µΜ), but inhibited by 6.05-49.85% from 5 to 100 µΜ. Excessive Cd accumulation induced oxidative injury manifesting higher MDA content, resulting in lower photosynthetic efficiency, stunted growth, and reduction of biomass. Further, the contents of ascorbate, glutathione, non-protein thiols, and phytochelatins were improved under 5-100 µΜ Cd treatment. The ascorbate peroxidase activity in the leaf showed a hormetic dose-response characteristic. Correlation analysis and partial least squares (PLS) results indicated that antioxidant enzymes and metabolites were closely correlated with Cd tolerance and accumulation. The results of the element network, correlation analysis, and PLS showed a crucial role for exogenous Cd levels in K, Fe, Cu, and Mn uptake and accumulation. These results provided a deeper understanding of the hormetic effect of Cd in wheat, which would be beneficial for improving the quality of hazard and risk assessments.

Transcriptome sequencing analysis reveals the molecular regulatory mechanism of myocardial hypertrophy induced by angiotensin II.

The pathogenesis of myocardial hypertrophy remains incompletely understood, highlighting the critical need for in-depth investigation into its pathogenesis and pathophysiology to develop innovative strategies for preventing and treating heart diseases. In this study, a model of angiotensin II (Ang II)-induced myocardial hypertrophy was established using subcutaneous administration with a micropump. Echocardiography, wheat germ agglutinin staining, and western blot analysis were used to evaluate the myocardial hypertrophy model after 5, 10, and 15 days of Ang II treatment. RNA-seq was employed to analyze the differential expression profile of mRNA, followed by bioinformatics analysis. Subsequently, the anti-inflammatory drug meloxicam was utilized to explore its impact on cardiac hypertrophy in mice. The findings demonstrated that mice developed myocardial hypertrophy following subcutaneous administration of Ang II. Transcriptomic analysis revealed significant changes in gene expression in the myocardium induced by Ang II, with the most pronounced differences observed at day 10. Functional analysis and verification of differentially expressed genes indicated that Ang II triggered an inflammatory response in the myocardium, leading to up-regulation of genes associated with fibrosis and apoptosis while decreasing energy metabolism; alterations were also observed in genes related to oxidative stress and calcium ion binding. Treatment with meloxicam improved Ang II-induced myocardial hypertrophy. This study not only elucidated the molecular regulatory mechanism underlying mouse myocardial hypertrophy at a transcriptional level but also provided new insights into clinical prevention and treatment strategies for cardiac diseases such as dilated cardiomyopathy and heart failure.

Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 µmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Role of FGF21 in mediating the effect of phosphatidylcholine on GBM.

Objective: The causal relationship and mechanisms between lipids and glioblastoma (GBM) remain unclear. This study aims to investigate the independent causal relationship between liposomal phosphatidylcholine 16:0_22:6 (PC16) and GBM, and to identify the potential mediating role of the inflammatory factor-fibroblast growth factor 21(FGF21). Methods: Utilizing summary statistics from genome-wide association studies (GWAS) of lipids (179 types in 7174 Finnish individuals), GBM (243 cases and 287137 controls), and inflammatory factors (91 types in 14824 European individuals), a two-sample Mendelian Randomization (MR) approach was employed to establish the causal link between liposomal PC16 and GBM. Additionally, a two-step MR method was used to quantify the proportion of the causal effect of PC16 on GBM that is mediated by the inflammatory factor FGF21. Results: MR analyses revealed a strong causal relationship between PC16 and GBM (OR=1.72, 95% CI: 1.11-2.68, P=0.016), but no reverse causality was observed from GBM to PC16 (OR=1.01, 95% CI: 0.99-1.02, P=0.38). Mediation analysis showed a strong causal relationship between PC16 and the FGF21 (OR = 0.94, 95% CI: 0.89-0.99, P=0.018) as well as between FGF21 and GBM (OR = 0.42, 95% CI: 0.25-0.71, P=0.001), with the mediation effect accounting for 9.78% of the total effect. This suggests that the causal relationship between PC16 and GBM is likely mediated by the intermediary factor FGF21. No evidence of pleiotropy was found in the sensitivity analysis of these positive results. Conclusion: In summary, the findings of this study suggest that liposomal PC16 may increase the risk of GBM occurrence, and FGF21 may play a significant mediating role in this causal relationship.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Analyzing Risk Factors for Delayed Extubation Following Posterior Approach Surgery for Congenital Scoliosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Investigate the risk factors for delayed extubation after posterior approach orthopedic surgery in patients with congenital scoliosis. METHODS: The clinical data of patients who received surgery for congenital scoliosis at the First Affiliated Hospital of Xinjiang Medical University between January 2021 and July 2023 have been gathered. Patients are categorized into the usual and the delayed extubation groups, depending on the duration of tracheal intubation after surgery. The study employs univariate and multivariate logistic regression models to examine the clinical characteristics of the two cohorts and discover potential risk factors linked to delayed extubation. In addition, a prediction model is created to visually depict the significance of each risk factor in terms of weight according to the nomogram. RESULTS: A total of 119 patients (74.8% females), with a median age of 15 years, are included. A total of 32 patients, accounting for 26.9% of the sample, encountered delayed extubation. Additionally, 13 patients (10.9%) suffered perioperative complications, with pneumonia being the most prevalent. The multivariate regression analysis revealed that the number of osteotomy segments, postoperative hematocrit, postoperative Interleukin-6 levels, and weight are predictive risk factors for delayed extubation. CONCLUSIONS: Postoperative hematocrit and Interleukin-6 level, weight, and number of osteotomy segments can serve as independent risk factors for predicting delayed extubation, with combined value to assist clinicians in evaluating the risk of delayed extubation of postoperative congenital scoliosis patients, improving the success rate of extubation, and reducing postoperative treatment time in the intensive care unit.

TouchMark: Partial Tactile Feedback Design for Upper Limb Rehabilitation in Virtual Reality.

The use of Virtual Reality (VR) technology, especially in medical rehabilitation, has expanded to include tactile cues along with visual stimuli. For patients with upper limb hemiplegia, tangible handles with haptic stimuli could improve their ability to perform daily activities. Traditional VR controllers are unsuitable for patient rehabilitation in VR, necessitating the design of specialized tangible handles with integrated tracking devices. Besides, matching tactile stimulation with corresponding virtual visuals could strengthen users' embodiment (i.e., owning and controlling virtual bodies) in VR, which is crucial for patients' training with virtual hands. Haptic stimuli have been shown to amplify the embodiment in VR, whereas the effect of partial tactile stimulation from tangible handles on embodiment remains to be clarified. This research, including three experiments, aims to investigate how partial tactile feedback of tangible handles impacts users' embodiment, and we proposed a design concept called TouchMark for partial tactile stimuli that could help users quickly connect the physical and virtual worlds. To evaluate users' tactile and comfort perceptions when grasping tangible handles in a non-VR setting, various handles with three partial tactile factors were manipulated in Study 1. In Study 2, we explored the effects of partial feedback using three forms of TouchMark on the embodiment of healthy users in VR, with various tangible handles, while Study 3 focused on similar investigations with patients. These handles were utilized to complete virtual food preparation tasks. The tactile and comfort perceptions of tangible handles and users' embodiment were evaluated in this research using questionnaires and interviews. The results indicate that TouchMark with haptic line and ring forms over no stimulation would significantly enhance users' embodiment, especially for patients. The low-cost and innovative TouchMark approach may assist users, particularly those with limited VR experience, in achieving the embodiment and enhancing their virtual interactive experience.

Penicipyrrolizidinones A-C, three pyrrolizidinone alkaloids with unprecedented skeletons from the mangrove-derived fungus Penicillium sp. DM27.

Three previously undescribed pyrrolizidinone alkaloids, penicipyrrolizidinones A and B (1 and 2), possessing an unprecedented 2-methyl-2-(oct-6-enoyl)pyrrolizidin-3-one skeleton, and penicipyrrolizidinone C (3), featuring a rare 1-alkenyl-2-methyl-pyrrolizidin-3,7-dione skeleton, together with four known pyrrolidine derivatives (4-7) were isolated from the mangrove-derived fungus Penicillium sp. DM27. Their structures were elucidated through comprehensive spectroscopic analysis, theoretical calculations of ECD spectra, and the modified Mosher's method. A plausible biosynthetic pathway for penicipyrrolizidinones A-C (1-3) was proposed. Compounds 4 and 5 exhibited moderate cytotoxicity against B16-F10 melanoma cells with IC50 values of 10.5 µM and 15.5 µM, respectively.

Branched hybridization chain reaction and tetrahedral DNA-based trivalent aptamer powered SERS sensor for ultra-highly sensitive detection of cancer-derived exosomes.

Exosomes have emerged as a promising noninvasive biomarker for early cancer diagnosis due to their ability to carry specific bioinformation related to cancer cells. However, accurate detection of trace amount of cancer-derived exosomes in complex blood remains a significant challenge. Herein, an ultra-highly sensitive SERS sensor, powered by the branched hybridization chain reaction (bHCR) and tetrahedral DNA-based trivalent aptamer (triApt-TDN), has been proposed for precise detection of cancer-derived exosomes. Taking gastric cancer SGC-7901 cells-derived exosomes as a test model, the triApt-TDNs were constructed by conjugating aptamers specific to mucin 1 (MUC1) protein with tetrahedral DNAs and subsequently immobilized on the surface of silver nanorods (AgNRs) arrays to create SERS-active sensing chips capable of specifically capturing exosomes overexpressing MUC1 proteins. The bHCR was further initiated by the trigger aptamers (tgApts) bound to exosomes, and as a result the SERS tags were assembled into AuNP network structures with abundant SERS hotspots. By optimizing the sensing conditions, the SERS sensor showed good performance in ultra-highly sensitive detection of target exosomes within 60 min detection time, with a broad response ranging of 1.44 to 1.44 × 104 particles·µL-1 and an ultralow limit of detection capable of detecting a single exosome in 2 µL sample. Furthermore, the SERS sensor exhibited good uniformity, repeatability and specificity, and capability to distinguish between gastric cancer (GC) patients and healthy controls (HC) through the detection of exosomes in clinical human serums, indicating its promising clinical potential for early diagnosis of gastric cancer.

Association between long-term exposure to PM2.5 chemical components and metabolic syndrome in middle-aged and older adults.

Background: Previous studies indicated that exposure to ambient fine particulate matter (PM2.5) could increase the risk of metabolic syndrome (MetS). However, the specific impact of PM2.5 chemical components remains uncertain. Methods: A national cross-sectional study of 12,846 Chinese middle-aged and older adults was conducted. Satellite-based spatiotemporal models were employed to determine the 3-year average PM2.5 components exposure, including sulfates (SO4 2-), nitrates (NO3 -), ammonia (NH4 +), black carbon (BC), and organic matter (OM). Generalized linear models were used to investigate the associations of PM2.5 components with MetS and the components of MetS, and restricted cubic splines curves were used to establish the exposure-response relationships between PM2.5 components with MetS, as well as the components of MetS. Results: MetS risk increased by 35.1, 33.5, 33.6, 31.2, 32.4, and 31.4% for every inter-quartile range rise in PM2.5, SO4 2-, NO3 -, NH4 +, OM and BC, respectively. For MetS components, PM2.5 chemical components were associated with evaluated risks of central obesity, high blood pressure (high-BP), high fasting glucose (high-FBG), and low high-density lipoprotein cholesterol (low-HDL). Conclusion: This study indicated that exposure to PM2.5 components is related to increased risk of MetS and its components, including central obesity, high-BP, high-FBG, and low-HDL. Moreover, we found that the adverse effect of PM2.5 chemical components on MetS was more sensitive to people who were single, divorced, or widowed than married people.

Developing and validating intracity spatiotemporal air quality health index in eastern China.

BACKGROUND: Recently pilot published city-level air quality health index (AQHI) provides a useful tool for communicating short-term health risks of ambient air pollution, but fails to account for intracity spatial heterogeneity in exposure and associated population health impacts. This study aims to develop the intracity spatiotemporal AQHI (ST-AQHI) via refined air pollution-related health risk assessments. METHODS: A three-stage analysis was conducted through integrating province-wide death surveillance data and high-resolution gridded estimates of air pollution and climate factors spanning 2016-2019 in Jiangsu Province, eastern China. First, an individual-level case-crossover design was employed to quantify the short-term risk of nonaccidental mortality associated with residential exposure to individual pollutant (i.e., PM2.5, NO2, O3, and SO2). Second, we accumulated and scaled the excess risks arising from multiple pollutants to formulate daily gridded ST-AQHI estimates at 0.1° × 0.1°, dividing exposure-related risks into low (0-3), moderate (4-6), high (7-9), and extreme high (10+) levels. Finally, the effectiveness of ST-AQHI as composite risk communication was validated through checking the dose-response associations of individual ST-AQHI exposure with deaths from nonaccidental and major cardiopulmonary causes via repeating case-crossover analyses. RESULTS: We analyzed a total of 1,905,209 nonaccidental death cases, comprising 785,567 from circulatory diseases and 247,336 from respiratory diseases. In the first-stage analysis, for each 10-µg/m3 rise in PM2.5, NO2, O3, and SO2 exposure at lag-01 day, population risk of nonaccidental death was increased by 0.8% (95% confidence interval: 0.7%, 0.9%), 1.9% (1.7%, 2.0%), 0.4% (0.3%, 0.5%), and 4.1% (3.7%, 4.5%), respectively. Spatiotemporal distribution of ST-AQHI exhibited a consistent declining trend throughout the study period (2016-2019), with annual average ST-AQHI decreasing from 5.2 ± 1.3 to 4.0 ± 1.0 and high-risk days dropping from 15.8% (58 days) to 1.6% (6 days). Exposure associated health risks showed great intracity- and between-city heterogeneities. In the validation analysis, ST-AQHI demonstrated approximately linear, threshold-free associations with multiple death events from nonaccidental and major cardiopulmonary causes, suggesting excellent performance in predicting exposure-related health risks. Specifically, each 1-unit rise in ST-AQHI was significantly associated with an excess risk of 2.0% (1.8%, 2.1%) for nonaccidental mortality, 2.3% (2.1%, 2.6%) for overall circulatory mortality, and 2.7% (2.3%, 3.1%) for overall respiratory mortality, as well as 1.7%-3.0% for major cardiopulmonary sub-causes. CONCLUSIONS: ST-AQHI developed in this study performed well in predicting intracity spatiotemporal heterogeneity of death risks related to multiple air pollutants, and may hold significant practical importance in communicating air pollution-related health risks to the public at the community scales.

The Effect of Low-Dose Dexmedetomidine on Perioperative Neurocognitive Dysfunction in Elderly Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized, Controlled, Double-Blind Trial.

Objective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 µg·kg-1·h-1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 µg·kg-1·h-1 and propofol at 1-2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-ß, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events. Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P<0.001), S100-ß (F=2681.964, P<0.001), and cortisol (F=137.637, P<0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P<0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups. Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence.

Myc-mediated inhibition of HIF1a degradation promotes M2 macrophage polarization and impairs CD8 T cell function through lactic acid secretion in ovarian cancer.

Ovarian cancer, the eleventh most prevalent cancer among women and a significant cause of cancer-related mortality, poses considerable challenges. While the Myc oncogene is implicated in diverse cancers, its impact on tumours expressing Myc during immune therapy processes remains enigmatic. Our study investigated Myc overexpression in a murine ovarian cancer cell line, focusing on alterations in HIF1a function. Seahorse experiments were utilized to validate metabolic shifts post-Myc overexpression. Moreover, we explored macrophage polarization and immunosuppressive potential following coculture with Myc-overexpressing tumour cells by employing Gpr132-/- mice to obtain mechanistic insights. In vivo experiments established an immune-competent tumour-bearing mouse model, and CD8 T cell, Treg, and macrophage infiltration post-Myc overexpression were evaluated via flow cytometry. Additionally, adoptive transfer of OTI CD8 T cells was conducted to investigate antigen-specific immune response variations after Myc overexpression. The findings revealed a noteworthy delay in HIF1a degradation, enhancing its functionality and promoting the classical Warburg effect upon Myc overexpression. Lactic acid secretion by Myc-overexpressing tumour cells promoted Gpr132-dependent M2 macrophage polarization, leading to the induction of macrophages capable of significantly suppressing CD8 T cell function. Remarkably, heightened macrophage infiltration in tumour microenvironments post-Myc overexpression was observed alongside impaired CD8 T cell infiltration and function. Interestingly, CD4 T-cell infiltration remained unaltered, and immune-suppressive effects were alleviated when Myc-overexpressing tumour cells were administered to Gpr132-/- mice, shedding light on potential therapeutic avenues for ovarian cancer management.

Using polycaprolactone and sodium alginate to prepare self-pumping/super-absorbent/transportable drug dressings for stage 3-4 pressure ulcer treatment.

Pressure ulcer dressings with different functions can enhance wound healing ability to varying degrees; however, pressure ulcer dressings that integrate various functions and break the resistance of bacteria to traditional antibiotics have not been widely studied. We proposed a self-pumping/super-absorbent/transportable drug dressing (PLD-SLD), polycaprolactone (PCL)/sodium alginate (SA) was used to load platelet-derived growth factor (PDGF) and lidocaine hydrochloride (LID) by Janus electrospinning and self-assembly technology, and Ɛ-polylysine was used as a biological bacteriostatic agent to prepare a multi-layer dressing. SEM showed that the dressing had a fluffy structure. The dressing can pump the exudate to the SA layer away from the skin. The swelling ratio reached 1378.667 ± 44.752 %. Coagulate blood in 5 min. On the 8th day, the unclosed area rate of the PLD-SLD dressing group was 16.112 ± 0.088 % lower than that of the model group. Importantly, the dressing can induce the expression of CD31, VEGF, α-SMA, and reduce the expression of CD68, thereby giving priority to wound healing. There was no scar formation after healing. In this study, a new dressing preparation method was proposed for the problems of exudate management, infection control, pain relief and healing promotion of stage 3-4 pressure ulcer healing.

MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination.

DNA double-strand break repair by homologous recombination has a specialised role in meiosis by generating crossovers that enable the formation of haploid germ cells. This requires meiosis-specific MEILB2-BRME1, which interacts with BRCA2 to facilitate loading of recombinases onto resected DNA ends. Here, we report the crystal structure of the MEILB2-BRME1 2:2 core complex, revealing a parallel four-helical assembly that recruits BRME1 to meiotic double-strand breaks in vivo. It forms an N-terminal ß-cap that binds to DNA, and a MEILB2 coiled-coil that bridges to C-terminal ARM domains. Upon BRCA2-binding, MEILB2-BRME1 2:2 complexes dimerize into a V-shaped 2:4:4 complex, with rod-like MEILB2-BRME1 components arranged at right-angles. The ß-caps located at the tips of the MEILB2-BRME1 limbs are separated by 25 nm, allowing them to bridge between DNA molecules. Thus, we propose that BRCA2 induces MEILB2-BRME1 to function as a DNA clamp, connecting resected DNA ends or homologous chromosomes to facilitate meiotic recombination.

Serum calcium level at 32 weeks of gestation could be applied as a predictor of preterm delivery: a retrospective study.

Preterm delivery (PTD) is associated with severe adverse maternal and neonatal outcomes and higher medical costs. Therefore, PTD warrants more attention. However, predicting PTD remains a challenge for researchers. This study aimed to investigate potential prenatal predictors of PTD. We retrospectively recruited pregnant women who experienced either PTD or term delivery (TD) and underwent laboratory examinations at 32 weeks of gestation. We compared the test results between the two groups and performed logistic regression analysis and receiver operating characteristic (ROC) curve analysis to identify risk factors and predictive factors for PTD. Our investigation revealed that the PTD cohort exhibited statistically significant elevations in lymphocyte count, mean corpuscular hemoglobin concentration, calcium, uric acid, alkaline phosphatase, triglycerides, and total bile acids. Conversely, the PTD group demonstrated statistically significant reductions in mean corpuscular volume, homocysteine, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), neutrophils to (white blood cells-neutrophils) ratio (dNLR), and (neutrophils × monocytes) to lymphocyte ratio (SIRI). The ROC curve analysis revealed that calcium had an area under the curve (AUC) of 0.705, with a cut-off value of 2.215. Logistic regression analysis showed that premature rupture of membranes was an independent risk factor for PTD. Our study demonstrated that serum calcium levels, NLR, dNLR, and other laboratory tests conducted at 32 weeks of gestation can serve as predictors for PTD. Furthermore, we identified premature rupture of membranes as a risk factor for PTD.

Orthodontic extrusion with fixed appliances for treatment of intrusive luxation injuries: A prospective study of 28 permanent maxillary incisors.

BACKGROUND: Limited evidence exists on the treatment options of tooth repositioning after intrusive luxation. AIM: The study aimed to investigate the outcomes and complications of orthodontic extrusion in treating intruded maxillary permanent incisors. DESIGN: A prospective study was conducted involving 28 intruded maxillary permanent incisors treated with orthodontic extrusion, compared with a retrospective control group of 29 teeth that underwent spontaneous re-eruption. The success rate of tooth repositioning, as well as pulp condition, periodontal healing, and root development were assessed and compared. RESULTS: The success rate of orthodontic extrusion was 96.4%, excluding one tooth that was ankylosed before treatment. There were no significant differences in pulp condition between the orthodontic extrusion and control groups for teeth with immature root development. Teeth with mature root development in the orthodontic group, however, showed a significantly higher rate of pulp necrosis (100%, p < .05). Periodontal healing outcomes were similar across both groups, regardless of the maturity of root development. The root length continued increasing during orthodontic extrusion treatment. CONCLUSIONS: Orthodontic extrusion treatment could effectively reposition moderately to severely intrusive permanent incisors, without increasing the risk of complications compared with spontaneous re-eruption.