Non-contact wide-field viewing system-assisted scleral buckling surgery for retinal detachment in silicone oil-filled eyes.

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

[Spatiotemporal Evolution and Influencing Factors of Ecosystem Service Value in the Yellow River Basin].

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

Functions of HP1 in preventing chromosomal instability.

Chromosomal instability (CIN), caused by errors in the segregation of chromosomes during mitosis, is a hallmark of many types of cancer. The fidelity of chromosome segregation is governed by a sophisticated cellular signaling network, one crucial orchestrator of which is Heterochromatin protein 1 (HP1). HP1 dynamically localizes to distinct sites at various stages of mitosis, where it regulates key mitotic events ranging from chromosome-microtubule attachment to sister chromatid cohesion to cytokinesis. Our evolving comprehension of HP1's multifaceted role has positioned it as a central protein in the orchestration of mitotic processes.

Palladium-catalyzed (Z)-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Exosomes Derived from Caerulein-Stimulated Pancreatic Acinar Cells Mediate Peritoneal Macrophage M1 Polarization and Pyroptosis via an miR-24-3p/MARCH3/NLRP3 Axis in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on caerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A caerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of caerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from caerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in caerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from caerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

Efficacy of neuroendoscopic-assisted surgery in the management of symptomatic sacral perineural (Tarlov) cysts: a technical report.

Introduction: The Tarlov cysts are pathological enlargements of the cerebrospinal fluid spaces between the endoneurium and perineurium, which can cause intolerable sciatic pain, motor impairment of lower limbs, and bladder/bowel dysfunction. Currently, the treatment results are unsatisfactory due to the low cure rates and extensive surgical trauma. Thus, there is an ongoing exploration of surgical techniques for Tarlov treatment. In the current study, we present a novel neuroendoscopic-assisted technique that combines the fenestration, leakage sealing, and tamponade of the Tarlov cyst. Methods: Between January 2020 and December 2021, a total of 32 Tarlov patients were enrolled and received neuroendoscopic-assisted surgery. Their pre- and post-surgical Visual Analogue Scale (VAS) scores, major complaints, and MR imaging were recorded for comparison. Results: 27 of 32 patients (84.4%) patients demonstrated immediate pain relief as their VAS scores decreased from 5.6 ± 1.5 to 2.5 ± 1.1 (p < 0.01) on the first day after surgery. At the 3-month follow-up, the patients' average VAS score continued to decrease (1.94 ± 0.8). Meanwhile, saddle paresthesia, urinary incontinence, and constipation were relieved in 6 (50%), 4 (80%), and 5 (41.7%), respectively, according to patients self-report. No surgical-related complication was observed in any of the cases. Discussion: We conclude that neuroendoscopic-assisted surgery is an effective surgical method for symptomatic Tarlov cysts with minimized complications.

Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

Estimated median density identifies donor age and sex differences in red blood cell biological age.

BACKGROUND: Donors possess heterogeneous red cell concentrates (RCCs) in terms of the biological age of their red blood cells (RBCs) as a direct result of various donor-dependent factors influencing rates of erythropoiesis. This study aimed to estimate the median biological age of RBCs in RCCs based on donor age and sex to investigate inherent differences in blood products' biological ages over hypothermic storage using estimated median densities (EMDs). STUDY DESIGN: Sixty RCCs were collected from four donor groups; male and female teenagers (17-19 years old) and seniors (75+ years old). A Percoll density-based separation approach was used to quantify the EMDs indicative of biological age. EMD and mean corpuscular hemoglobin (MCHC) were compared by correlation analyses. RESULTS: Differences in the median biological age of RCC units were observed with male donors having significantly higher EMDs compared to females (p < .001). Teen male donors possessed the highest EMDs with significantly elevated levels of biologically aged RBCs compared to both female donor groups, regardless of storage duration (p < .05). Throughout most of the 42-day storage period, senior donors, particularly senior females, demonstrated the strongest correlation between EMD and MCHC (R2 > 0.5). CONCLUSIONS: This study provides further evidence that there are inherent differences between the biological age profiles of RBCs between blood donors of different sex and age. Our findings further highlight that biological age may contribute to RBC quality during storage and that donor characteristics need to be considered when evaluating transfusion safety and efficacy.

Clinical internship environment and caring behaviours among nursing students: A moderated mediation model.

BACKGROUND: Caring behaviour is critical for nursing quality, and the clinical internship environment is a crucial setting for preparing nursing students for caring behaviours. Evidence about how to develop nursing students' caring behaviour in the clinical environment is still emerging. However, the mechanism between the clinical internship environment and caring behaviour remains unclear, especially the mediating role of moral sensitivity and the moderating effect of self-efficacy. RESEARCH OBJECTIVE: This study aimed to examine the mediating effect of moral sensitivity and the moderating function of self-efficacy on the association between the clinical internship environment and caring behaviours. RESEARCH DESIGN: A cross-sectional design used acceptable validity scales. The hypothesised moderated mediation model was tested in the SPSS PROCESS macro. PARTICIPANTS AND RESEARCH CONTEXT: This survey collected data from 504 nursing students in an internship at a teaching hospital in Changsha, China. ETHICAL CONSIDERATIONS: This study was pre-approved by the ethics committee of the medical school (No. E2022210). Informed consent was obtained from all students. RESULTS: The clinical internship environment (B = 0.450, 95% CI = [0.371, 0.530]) and moral sensitivity (B = 1.352, 95% CI = [1.090, 1.615]) had positive direct effects on nursing students' caring behaviours. Clinical internship environment also indirectly influenced students' caring behaviours via moral sensitivity (B = 0.161, 95% CI = [0.115, 0.206]). In addition, self-efficacy played a moderating role between the clinical internship environment and caring behaviours (B = 0.019, 95% CI = [0.007, 0.031]), as well as the relationship between the clinical internship environment and moral sensitivity (B = 0.006, 95% CI = [0.003, 0.010]). CONCLUSION: Moral sensitivity mediates the effect of the clinical internship environment on caring behaviour, and self-efficacy strengthens both direct and indirect effects. This study emphasises the importance of self-efficacy in developing moral sensitivity and caring behaviours in nursing students.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report.

BACKGROUND: Human epidermal growth factor receptor-2 (HER-2) plays a vital role in tumor cell proliferation and metastasis. However, the prognosis of HER2-positive gastric cancer is poor. Inetetamab, a novel anti-HER2 targeting drug independently developed in China, exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab, which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy. In this case, the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer. CASE SUMMARY: A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension, poor appetite, and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery, followed by tegafur monotherapy for six months. The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma. He received 17 cycles of a combination of inetetamab, an innovative domestically developed anti-HER2 monoclonal antibody, and tegafur chemotherapy as the second-line treatment (inetetamab 200 mg on day 1, every 3 wk combined with tegafur twice daily on days 1-14, every 3 wk). Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months. He tolerated the treatment well without exhibiting any grade 3-4 adverse events. CONCLUSION: Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Red cell concentrates from teen male donors contain poor-quality biologically older cells.

BACKGROUND AND OBJECTIVES: Donor factors influence the quality characteristics of red cell concentrates (RCCs) and the lesions that develop in these heterogeneous blood products during hypothermic storage. Teen male donors' RCCs contain elevated levels of biologically old red blood cells (RBCs). The aim of this study was to interrogate the quality of units of different donor ages and sexes to unravel the complex interplay between donor characteristics, long-term cold storage and, for the first time, RBC biological age. MATERIALS AND METHODS: RCCs from teen males, teen females, senior males and senior females were density-separated into less-dense/young (Y-RBCs) and dense/old RBCs (O-RBCs) throughout hypothermic storage for testing. The unseparated and density-separated cells were tested for haematological parameters, stress (oxidative and osmotic) haemolysis and oxygen affinity (p50). RESULTS: The O-RBCs obtained from teen donor samples, particularly males, had smaller mean corpuscular volumes and higher mean corpuscular haemoglobin concentrations. While biological age did not significantly affect oxygen affinity, biologically aged O-RBCs from stored RCCs exhibited increased oxidative haemolysis and decreased osmotic fragility, with teenage male RCCs exhibiting the highest propensity to haemolyse. CONCLUSION: Previously, donor age and sex were shown to have an impact on the biological age distribution of RBCs within RCCs. Herein, we demonstrated that RBC biological age, particularly O-RBCs, which are found more prevalently in male teens, to be a driving factor of several aspects of poor blood product quality. This study emphasizes that donor factors should continue to be considered for their potential impacts on transfusion outcomes.

Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.

Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.

Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma.

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.

Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells.

OBJECTIVES: We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE. METHODS: Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network. RESULTS: There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell. CONCLUSIONS: The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Association Study of Esomeprazole Pharmacokinetics and CYP2C19 Gene Polymorphisms.

To investigate the association between esomeprazole pharmacokinetics and CYP2C19 gene polymorphisms in a cohort of 95 healthy Chinese participants. A cohort of 95 participants was assembled and stratified into 2 distinct groups, receiving either 20 or 40 mg of esomeprazole through oral administration. The subjects encompassed 17 poor metabolizers, 47 intermediate metabolizers, and 31 rapid metabolizers, and their genotypes were ascertained using the polymerase chain reaction-restriction fragment length polymorphism technique. Esomeprazole plasma concentrations were quantified employing a high-performance liquid chromatography-ultraviolet method. Pharmacokinetic parameters were computed via Phoenix WinNonlin 6.1 software, while SPSS 26.0 facilitated statistical analysis to contrast the pharmacokinetics and the CYP2C19 genotypes. In the aftermath of administering 20 or 40 mg esomeprazole, marked differences were discerned between terminal elimination half-life, maximum concentration/dose, and area under the plasma concentration-time curve from time zero to infinity/dose of esomeprazole (P < .05), with the exception of time to maximum concentration. The findings of this investigation signify a significant association between esomeprazole metabolism and CYP2C19 gene polymorphisms. There were no unprecedented adverse events documented subsequent to the administration of 20 and 40 mg esomeprazole dosages. Esomeprazole has manifested promising safety and tolerability profiles in pertinent clinical trials.

The association between homocysteine and bacterial vaginosis: results from NHANES 2001-2004.

Although no study has directly shown the relationship between bacterial vaginosis (BV) and homocysteine (HCY), we still found some association between these two through extensive literature and data analysis. BV score was calculated by Nugent's method, less than equal to 6 is negative and greater than equal to 7 is positive. This article describes interrelationships we mined from data extracted by NHANES regarding BV and HCY under multiple covariates. We used two cycles of NHANES 2001-2002 and 2003-2004 in our study. We included 2398 participants in our study who recently completed the interview and the MEC tests. By investigating the relationship between BV and HCY under multivariate conditions, multiple linear regression analysis was performed. These factors may have influenced the results, such as ethnicity, age, education level, body mass index (BMI), etc. Serum vitamin B12, ferritin, percentage of segmented centrioles, and number of segmented centrioles were selected as potential covariates in our study. We observed that both the coarse model and the two adjusted models showed a high correlation between HCY and BV, and the correlation was positive. In the coarse model, OR = 1.26, 95% confidence interval (CI) 1.10, 1.44, P = 0.0018); HCY was positively correlated with BV (OR = 1.19, 95% confidence interval (CI) 1.05, 1.34, P = 0.0121). Multiple linear regression analysis was used to investigate the connection between BV and HCY under multivariate settings. The results of this study indicate that HCY is positively associated with the prevalence of BV and may play an important role in the prevention and management of BV.

Atomically accurate site-specific ligand tailoring of highly acid- and alkali-resistant Ti(iv)-based metallamacrocycle for enhanced CO2 photoreduction.

Skillfully engineering surface ligands at specific sites within robust clusters presents both a formidable challenge and a captivating opportunity. Herein we unveil an unprecedented titanium-oxo cluster: a calix[8]arene-stabilized metallamacrocycle (Ti16L4), uniquely crafted through the fusion of four "core-shell" {Ti4@(TBC[8])(L)} subunits with four oxalate moieties. Notably, this cluster showcases an exceptional level of chemical stability, retaining its crystalline integrity even when immersed in highly concentrated acid (1 M HNO3) and alkali (20 M NaOH). The macrocycle's surface unveils four specific, customizable µ2-bridging sites, primed to accommodate diverse carboxylate ligands. This adaptability is highlighted through deliberate modifications achieved by alternating crystal soaking in alkali and carboxylic acid solutions. Furthermore, Ti16L4 macrocycles autonomously self-assemble into one-dimensional nanotubes, which subsequently organize into three distinct solid phases, contingent upon the specific nature of the four µ2-bridging ligands. Notably, the Ti16L4 exhibit a remarkable capacity for photocatalytic activity in selectively reducing CO2 to CO. Exploiting the macrocycle's modifiable shell yields a significant boost in performance, achieving an exceptional maximum CO release rate of 4.047 ± 0.243 mmol g-1 h-1. This study serves as a striking testament to the latent potential of precision-guided surface ligand manipulation within robust clusters, while also underpinning a platform for producing microporous materials endowed with a myriad of surface functionalities.

Structural insights into the regulation, ligand recognition, and oligomerization of bacterial STING.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling pathway plays a critical protective role against viral infections. Metazoan STING undergoes multilayers of regulation to ensure specific signal transduction. However, the mechanisms underlying the regulation of bacterial STING remain unclear. In this study, we determined the crystal structure of anti-parallel dimeric form of bacterial STING, which keeps itself in an inactive state by preventing cyclic dinucleotides access. Conformational transition between inactive and active states of bacterial STINGs provides an on-off switch for downstream signaling. Some bacterial STINGs living in extreme environment contain an insertion sequence, which we show codes for an additional long lid that covers the ligand-binding pocket. This lid helps regulate anti-phage activities. Furthermore, bacterial STING can bind cyclic di-AMP in a triangle-shaped conformation via a more compact ligand-binding pocket, forming spiral-shaped protofibrils and higher-order fibril filaments. Based on the differences between cyclic-dinucleotide recognition, oligomerization, and downstream activation of different bacterial STINGs, we proposed a model to explain structure-function evolution of bacterial STINGs.