Association Between Shift Work and Clean Room Environment on Self-reported Premenstrual Symptoms and Menstrual Pain in Taiwan.

Background: Limited research has delved into the effects of work characteristics on premenstrual symptoms (PMS) in women, which can influence work performance and overlook potential hazards for women in their work environments. This study aimed to investigate the impact of shift work and working in a clean room on premenstrual symptoms, menstrual status, and menstrual pain among employed females in an electronics manufacturer. Methods: A retrospective cohort study was conducted on menstruating female employees between August and December 2014, aged 18-55, who received regular employee health checks. Questionnaires were designed to collect information on demographics, personal lifestyle, menstrual status, menstrual pain scores, and self-reported premenstrual symptoms. Results: Among 7,193 participants, 18.6% reported moderate to severe menstrual pain affecting their work. Female workers who reported shift work showed an increased prevalence of moderate to severe premenstrual symptoms, including fatigue (RR = 1.20), somatic discomforts (RR = 1.04), diarrhea (RR = 1.04), and tension (RR = 1.05). Additionally, shift work was associated with an elevated risk of experiencing a moderate or significant impact of menstrual pain on work (RR = 1.03), menstrual irregularity (RR = 1.30), and high menstrual pain (RR = 1.23). Working in a clean room was associated with an increased risk of high menstrual pain (RR = 1.13). Subjects working shifts in a clean room had the highest pain scores compared to the other groups. Conclusion: This study underscores the association of work-related factors on PMS in female employees. Our findings contribute to a better understanding of premenstrual symptoms in female workers with different work characteristics, emphasizing the potential hazards of work-related factors on female employees.

Mechanochromic and Solvent-Induced Luminescence of a Supramolecular Pt(II)-Bipyridine Complex with Di(4-pyridylmethyl)aminedithiocarbamate.

[Pt(bpy)(DPMACS2)]2Cl2•3H2O (1•3H2O) (bpy = 2,2'-bipyridine, DPMACS2 = di(4-pyridylmethyl)aminedithiocarbamate) was synthesized and characterized by X-ray diffraction studies, and its crystal structure displayed intermolecular Pt(II)···Pt(II) contacts of 3.471 and 5.065 Å. Upon excitation, 1•3H2O showed broad luminescence at 538 nm, which was red-shifted and enhanced to 560 nm while cooling to 77 K. To this end, the B3LYP/LanL2DZ calculation results were performed to clearly explain their excited-state origin. Moreover, complex 1•3H2O displayed a dramatic mechanochromic shift from 538 to 608 nm while grinding, and the above red-shift was also observed while exposed to air within 1 day, suggestive of the simultaneous mechanochromic and solvent-induced luminescence. It is noted that the luminescence almost reverted to the original luminescence at 535-542 nm upon immersion in various solvents for the ground samples of complex 1•3H2O. In addition, the luminescence for the acetone-immersed ground samples returned to 608 nm in 1 min. The possible interactions between halogenated solvents and the free pyridyl groups in DPMACS2, which were not expected for acetone, have been proposed to be responsible for such a dramatic difference in this study.

Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery. METHODS: This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. RESULTS: A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; P=0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. CONCLUSIONS: Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568.

Prevalence and correlations of schistosomiasis mansoni and schistosomiasis haematobium among humans and intermediate snail hosts: a systematic review and meta-analysis.

BACKGROUND: The control of schistosomiasis is particularly difficult in sub-Saharan Africa, which currently harbours 95% of this disease. The target population for preventive chemotherapy (PC) is expanded to all age group at risk of infection, thus increasing the demands of praziquantel (PZQ) tablets according to the new released guideline by World Health Organization. Due to the gap between available PZQ for PC and requirements, alternative approaches to assess endemicity of schistosomiasis in a community, are urgently needed for more quick and precise methods. We aimed to find out to which degree the infection status of snails can be used to guide chemotherapy against schistosomiasis. METHODS: We searched literature published from January 1991 to December 2022, that reported on the prevalence rates of Schistosoma mansoni, S. haematobium in the intermediate snails Biomphalaria spp. and Bulinus spp., respectively, and in humans. A random effect model for meta-analyses was used to calculate the pooled prevalence estimate (PPE), with heterogeneity assessed using I-squared statistic (I2), with correlation and regression analysis for the exploration of the relationship between human S. mansoni and S. haematobium infections and that in their specific intermediate hosts. RESULTS: Forty-seven publications comprising 59 field investigations were included. The pooled PPE of schistosomiasis, schistosomiasis mansoni and schistosomiasis haematobium in humans were 27.5% [95% confidence interval (CI): 24.0-31.1%], 25.6% (95% CI: 19.9-31.3%), and 28.8% (95% CI: 23.4-34.3%), respectively. The snails showed an overall infection rate of 8.6% (95% CI: 7.7-9.4%), with 12.1% (95% CI: 9.9-14.2%) in the Biomphalaria spp. snails and 6.9% (95% CI: 5.7-8.1%) in the Bulinus spp. snails. The correlation coefficient was 0.3 (95% CI: 0.01-0.5%, P < 0.05) indicating that the two variables, i.e. all intermediate host snails on the one hand and the human host on the other, were positively correlated. CONCLUSIONS: The prevalence rate of S. mansoni and S. haematobium is still high in endemic areas. Given the significant, positive correlation between the prevalence of schistosomes in humans and the intermediate snail hosts, more attention should be paid to programme integration of snail surveillance in future.

Single-cell transcriptomic landscape reveals the role of intermediate monocytes in aneurysmal subarachnoid hemorrhage.

Objective: Neuroinflammation is associated with brain injury and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). In this study, we performed single-cell RNA sequencing (scRNA-seq) to analyze monocytes and explore the mechanisms of neuroinflammation after SAH. Methods: We recruited two male patients with SAH and collected paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from each patient. Mononuclear cells from the CSF and PB samples were sequenced using 10x Genomics scRNA-seq. Additionally, scRNA-seq data for CSF from eight healthy individuals were obtained from the Gene Expression Omnibus database, serving as healthy controls (HC). We employed various R packages to comprehensively study the heterogeneity of transcriptome and phenotype of monocytes, including monocyte subset identification, function pathways, development and differentiation, and communication interaction. Results: (1) A total of 17,242 cells were obtained in this study, including 7,224 cells from CSF and 10,018 cells from PB, mainly identified as monocytes, T cells, B cells, and NK cells. (2) Monocytes were divided into three subsets based on the expression of CD14 and CD16: classical monocytes (CM), intermediate monocytes (IM), and nonclassical monocytes (NCM). Differentially expressed gene modules regulated the differentiation and biological function in monocyte subsets. (3) Compared with healthy controls, both the toll-like receptor (TLR) and nod-like receptor (NLR) pathways were significantly activated and upregulated in IM from CSF after SAH. The biological processes related to neuroinflammation, such as leukocyte migration and immune response regulation, were also enriched in IM. These findings revealed that IM may play a key role in neuroinflammation by mediating the TLR and NLR pathways after SAH. Interpretation: In conclusion, we establish a single-cell transcriptomic landscape of immune cells and uncover the heterogeneity of monocyte subsets in SAH. These findings offer new insights into the underlying mechanisms of neuroinflammation and therapeutic targets for SAH.

Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy.

AIM: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). METHODS: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. RESULTS: The CNFD was reduced in glaucoma groups compared to healthy subjects (P<0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P<0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups (P<0.001). In the absence of medication, CNFD in males was lower than that in females (P<0.05). Among patients under medication therapy, CNFD remained consistent between males and females. CONCLUSION: Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Remifentanil vs. dexmedetomidine for cardiac surgery patients with noninvasive ventilation intolerance: a multicenter randomized controlled trial.

BACKGROUND: The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. METHODS: In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. RESULTS: A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3-3 vs. 3, IQR 3-4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35-8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8-12 days vs. 7.0 days, IQR 5-10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. CONCLUSIONS: In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

Effects of nutrient ratios on a newly harmful dinoflagellate Heterocapsa bohaiensis: Evidence from growth, toxicity and transcriptome analyses.

Heterocapsa bohaiensis is a newly identified dinoflagellate species that causes harmful blooms in coastal areas in China, Malaysian, and New Caledonian. These blooms have led to substantial economic losses for local aquaculture. Previous studies have mainly focused on understanding the toxicity of H. bohaiensis. However, the causes of H. bohaiensis blooms remain unknown. In this study, we aimed to ascertain nitrogen (N) and phosphorus (P) requirements for the growth and reproduction of H. bohaiensis. Additionally, we sought to understand the functional mechanisms by comparing the transcriptomes of H. bohaiensis under nutrient-limited conditions and control conditions. The results revealed a wide range of acceptable N:P ratios for H. bohainensis, attributed to a mechanism involving nutrient storage, which allowed H. bohainensis to sustain its growth even when either nitrate or phosphate was depleted. Higher N:P ratios (>27.5) were more conducive to the growth of H. bohainensis than f/2 medium or low ratios, which is related to the N:P ratios absorbed by H. bohainensis. The toxicity of H. bohainensis was significantly enhanced in N-limited or P-limited states. These findings underscore the significance of the physiological metabolism of H. bohainensis in adapting to environmental stresses induced by human activities and establishing the dominance of blooms.

Oncofetal TRIM71 drives liver cancer carcinogenesis through remodeling CEBPA-mediated serine/glycine metabolism.

Rationale: Tumor cells remodel transcriptome to construct an ecosystem with stemness features, which maintains tumor growth and highly malignant characteristics. However, the core regulatory factors involved in this process still need to be further discovered. Methods: Single cell RNA-sequncing (scRNA-seq) and bulk RNA-sequencing profiles derived from fetal liver, normal liver, liver tumors, and their adjacent samples were collected to analyze the ecosystem of liver cancer. Mouse models were established to identify molecular functions of oncofetal-related oncogenes using hydrodynamic tail vein injection. Results: We found that liver cancer rebuilt oncofetal ecosystem to maintain malignant features. Interestingly, we identified a group of RNA-binding proteins (RBPs) that were highly overexpressed with oncofetal features. Among them, TRIM71 was specifically expressed in liver cancers and was associated with poor outcomes. TRIM71 drove the carcinogenesis of hepatocellular carcinoma (HCC), and knockdown of TRIM71 significantly abolished liver cancer cell proliferation. Mechanistically, TRIM71 formed a protein complex with IGF2BP1, bound to and stabilized the mRNA of CEBPA in an m6A-dependent manner, enhance the serine/glycine metabolic pathway, and ultimately promoted liver cancer progression. Furthermore, we identified that all-trans-retinoic acid (ATRA) combined with e1A binding protein p300 (EP300) inhibitor A-485 repressed TRIM71, attenuated glycine/serine metabolism, and inhibited liver cancer cell proliferation with high TRIM71 levels. Conclusions: We demonstrated the oncofetal status in liver cancer and highlighted the crucial role of TRIM71 and provided potential therapeutic strategies and liver cancer-specific biomarker for liver cancer patients.

High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells.

OBJECTIVE: High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood. METHODS: Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels. RESULTS: The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway. CONCLUSION: These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.

Deep learning-assisted distinguishing breast phyllodes tumors from fibroadenomas based on ultrasound images: a diagnostic study.

OBJECTIVES: To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumors (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. METHODS: We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting six radiologists with different levels of experience. RESULTS: Upon testing, Xception model demonstrated the best diagnostic performance (AUC: 0.87, 95%CI: 0.81-0.92), outperforming all radiologists (all p < 0.05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. CONCLUSIONS: The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). ADVANCES IN KNOWLEDGE: We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate two types of breast tumors which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

Maternal separation during lactation affects recognition memory, emotional behaviors, hippocampus and gut microbiota composition in C57BL6J adolescent female mice.

BACKGROUND: Maternal separation (MS) in rodents is a paradigm of early life events that affects neurological development in depression. Adolescence is a time of dramatic increases in psychological vulnerability, and being female is a depression risk factor. However, data on whether different MS scenarios affect behavioral deficits and the potential mechanisms in adolescent female mice are limited. METHODS: C57BL/6 J female pups were exposed to different MS (no MS, NMS; MS for 15 min/day, MS15; or 180 min/day, MS180) from postnatal day (PND)1 to PND21 and subjected for behavioral tests during adolescence. Behavioural tests, specifically the open field test (OFT), novel object recognition test (NOR) test and tail suspension test (TST), were performed. The expression of proinflammatory cytokines, hippocampal neurogenesis, neuroinflammation, and gut microbiota were also assessed. RESULTS: The results showed that MS180 induced emotional behavioral deficits and object recognition memory impairment; however, MS15 promoted object recognition memory in adolescent females. MS180 decreased hippocampal neurogenesis of adolescent females, induced an increase in microgliosis, and increased certain inflammatory factors in the hippocampus, including TNF-α, IL-1ß, and IL-6. Furthermore, different MS altered gut microbiota diversity, and alpha diversity in the Shannon index was negatively correlated with the peripheral inflammatory factors TNF-α, IL-1ß, and IL-6. Species difference analysis showed that the gut microbiota composition of the phyla Desulfobacterota and Proteobacteria was affected by the MS. LIMITATIONS: The sex differences in adolescent animal and causality of hippocampal neurogenesis and gut microbiota under different MS need to be further analyzed in depression. CONCLUSION: This study indicates different MS affect recognition memory and emotional behaviors in adolescent females, and gut microbiota-neuroinflammation and hippocampal neurogenesis may be a potential site of early neurodevelopmental impairment in depression.

Carbon quantum dots for the diagnosis and treatment of ophthalmic diseases.

Carbon quantum dots (CQDs), an emerging nanomaterial, are gaining attention in ophthalmological applications due to their distinctive physical, chemical, and biological characteristics. For example, their inherent fluorescent capabilities offer a novel and promising alternative to conventional fluorescent dyes for ocular disease diagnostics. Furthermore, because of the excellent biocompatibility and minimal cytotoxicity, CQDs are well-suited for therapeutic applications. In addition, functionalized CQDs can effectively deliver drugs to the posterior part of the eyeball to inhibit neovascularization. This review details the use of CQDs in the management of ophthalmic diseases, including various retinal diseases, and ocular infections. While still in its initial phases within ophthalmology, the significant potential of CQDs for diagnosing and treating eye conditions is evident.

Integrative genomics reveals the polygenic basis of seedlessness in grapevine.

Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a ∼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.

Assessing the predictive value of elevated postoperative syndecan-1 levels for progressive acute kidney injury and kidney replacement therapy necessity in adult cardiac surgery patients.

BACKGROUND: The development of acute kidney injury (AKI) post-cardiac surgery significantly increases patient morbidity and healthcare costs. Prior researches have established Syndecan-1 (SDC-1) as a potential biomarker for endothelial injury and subsequent acute kidney injury development. This study assessed whether postoperative SDC-1 levels could further predict AKI requiring kidney replacement therapy (AKI-KRT) and AKI progression. METHODS: In this prospective study, 122 adult cardiac surgery patients, who underwent valve or coronary artery bypass grafting (CABG) or a combination thereof and developed AKI within 48 h post-operation from May to September 2021, were monitored for the progression to stage 2-3 AKI or the need for KRT. We analyzed the predictive value of postoperative serum SDC-1 levels in relation to multiple endpoints. RESULTS: In the study population, 110 patients (90.2%) underwent cardiopulmonary bypass, of which thirty received CABG or combined surgery. Fifteen patients (12.3%) required KRT, and thirty-eight (31.1%) developed progressive AKI, underscoring the severe AKI incidence. Multivariate logistic regression indicated that elevated SDC-1 levels were independent risk factors for progressive AKI (OR = 1.006) and AKI-KRT (OR = 1.011). The AUROC for SDC-1 levels in predicting AKI-KRT and AKI progression was 0.892 and 0.73, respectively, outperforming the inflammatory cytokines. Linear regression revealed a positive correlation between SDC-1 levels and both hospital (ß = 0.014, p = 0.022) and ICU stays (ß = 0.013, p < 0.001). CONCLUSION: Elevated postoperative SDC-1 levels significantly predict AKI progression and AKI-KRT in patients following cardiac surgery. The study's findings support incorporating SDC-1 level monitoring into post-surgical care to improve early detection and intervention for severe AKI.

Halogenated retinoid derivatives as dual RARα and RXRα modulators for treating acute promyelocytic leukemia cells.

Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα's tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL. Here, we developed a pair of brominated retinoid isomers, 5a and 5b, exhibiting RARα agonistic selectivity among the RAR subtypes and RXRα partial agonistic activities. In the treatment of APL cells, low doses (RARα activation range) of 5a and 5b degrade PML-RARα and strongly induce differentiation, while higher doses (RXRα activation range) induce G2/M arrest and apoptosis in both all-trans retinoic acid (ATRA)-sensitive and resistant cells. We replaced the bromine in 5a with chlorine or iodine to obtain compounds 7 or 8a. Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.

Racial and ethnic differences in second primary lung cancer risk among lung cancer survivors.

BACKGROUND: Recent therapeutic advances have improved survival among lung cancer (LC) patients, who are now at high risk of second primary lung cancer (SPLC). Hispanics comprise the largest minority in the United States, who have shown a lower LC incidence and mortality than other races, and yet their SPLC risk is poorly understood. We quantified the SPLC incidence patterns among Hispanics vs other races. METHODS: We used data from the Multiethnic Cohort, a population-based cohort of 5 races (African American, Japanese American, Hispanic, Native Hawaiian, and White), recruited between 1993 and 1996 and followed through 2017. We identified patients diagnosed with initial primary lung cancer (IPLC) and SPLC via linkage to Surveillance, Epidemiology, and End Results registries. We estimated the 10-year cumulative incidence of IPLC (in the entire cohort) and SPLC (among IPLC patients). A standardized incidence ratio (SIR) was calculated as the ratio of SPLC-to-IPLC incidence by race and ethnicity. RESULTS: Among 202 692 participants, 6788 (3.3%) developed IPLC over 3 871  417 person-years. The 10-year cumulative IPLC incidence was lower among Hispanics (0.80%, 0.72 to 0.88) vs Whites (1.67%, 1.56 to 1.78) or Blacks (2.44%, 2.28 to 2.60). However, the 10-year SPLC incidence following IPLC was higher among Hispanics (3.11%, 1.62 to 4.61) vs Whites (2.80%, 1.94 to 3.66) or Blacks (2.29%, 1.48 to 3.10), resulting in a significantly higher SIR for Hispanics (SIR = 8.27, 5.05 to 12.78) vs Whites (SIR = 5.60, 4.11 to 7.45) or Blacks (SIR = 3.48, 2.42 to 4.84; P < .001). CONCLUSION: Hispanics have a higher SPLC incidence following IPLC than other races, which may be potentially due to better survival after IPLC and extended duration for SPLC development. Continuing surveillance is warranted to reduce racial disparities among LC survivors.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

Research progress of brain organoids in the field of diabetes.

Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.