Cervical vertigo due to rotational fixation of atlantoaxial joint combined with benign paroxysmal positional vertigo: A case report and literature review.

INTRODUCTION: Vertigo is the most common clinical complaint, misdiagnosed patients are not rare, so it is very important to exclude and identify vertigo. For vertigo caused by multiple causes, including cervical vertigo with atlantoaxial rotation fixation combined with benign paroxysmal positional vertigo (BPPV), tuina can correct joint misalignment. The reduction technique will return the fallen otolith to the correct position. The use of massage and reduction can improve clinical symptoms and improve quality of life and may be a simple, safe, and effective treatment strategy for this disease. PATIENT CONCERNS: We report on a patient with both cervical vertigo due to atlantoaxial rotational fixation and BPPV, including his imaging examination, clinical manifestations, and treatment methods. DIAGNOSIS: Cervical vertigo (atlantoaxial rotatory fixation) and BPPV. INTERVENTION: Tuina combined with atlantoaxial directional inverted reduction technique and reduction manipulation. OUTCOMES: The patient's vertigo symptoms improved significantly, nystagmus disappeared, cervical occipital pain, nausea, head distension, and other symptoms disappeared, and cervical motion rotation reached 60°. CONCLUSION: This study proved the effectiveness of massage combined with a reduction in the treatment of cervical vertigo and BPPV, as well as the importance of vertigo diagnosis and differential diagnosis, and provided a new treatment idea for the future diagnosis and treatment of vertigo caused by a variety of causes.

Crizotinib and its enantiomer suppress ferroptosis by decreasing PE-O-PUFA content.

Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Stage-dependent role of interhemispheric pathway for motor recovery in primates.

Whether and how the non-lesional sensorimotor cortex is activated and contributes to post-injury motor recovery is controversial. Here, we investigated the role of interhemispheric pathway from the contralesional to ipsilesional premotor cortex in activating the ipsilesional sensorimotor cortex and promoting recovery after lesioning the lateral corticospinal tract at the cervical cord, by unidirectional chemogenetic blockade in macaques. The blockade impaired dexterous hand movements during the early recovery stage. Electrocorticographical recording showed that the low frequency band activity of the ipsilesional premotor cortex around movement onset was decreased by the blockade during the early recovery stage, while it was increased by blockade during the intact state and late recovery stage. These results demonstrate that action of the interhemispheric pathway changed from inhibition to facilitation, to involve the ipsilesional sensorimotor cortex in hand movements during the early recovery stage. The present study offers insights into the stage-dependent role of the interhemispheric pathway and a therapeutic target in the early recovery stage after lesioning of the corticospinal tract.

PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress.

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

Arginine Acts as both Co-solvent and Catalyst in Regioselective Eutectic-Mediated Dimerization of Levulinic Acid.

Invited for this issue's cover are Procter & Gamble's Corporate Analytical and Engineering Groups, along with the group of Professor Jovica Badjic and colleagues. The image, by Jennifer F. Neal, depicts the process of chemically upgrading the renewable, biomass-derived levulinic acid by simplying mixing it with l-arginine. The Research Article itself is available at 10.1002/cssc.202400503.

Arginine Acts as both Co-Solvent and Catalyst in Regioselective Eutectic-Mediated Dimerization of Levulinic Acid.

A simple, solvent-free arginine-catalyzed aldol dimerization of levulinic acid was achieved via the simultaneous formation of a eutectic mixture. Dimers of levulinic acid are valued as biomass-derived fine chemical precursors, with potential to upgrade to bio-jet fuels or N-containing functional chemicals. Typically, these dimers are produced as isomeric mixtures using high temperatures and a variety of solid inorganic catalysts or mineral acids. In this study, an organocatalytic and regioselective dimerization was achieved at 22 % conversion on either a bench or kilogram scale using mild temperatures and only L-arginine as both a co-solvent and catalyst. The intricate H-bonding network comprising the eutectic solvent was harnessed to produce only one product, minimizing side reactivity and preserving the reactants for recycling.

Portable one-step effervescence tablet-based microextraction combined with smartphone digital image colorimetry: Toward field and rapid detection of trace nickel ion.

In this study, the one-step switchable hydrophilic solvent (SHS)-based effervescence tablet microextraction (ETME) was coupled with smartphone digital image colorimetry (SDIC) for the field detection of nickel ion (Ni2+) for the first time. Both extractant and CO2 were generated in situ when the novel SHS-based effervescence tablet was placed in the sample solution. The complexant 1-(2-pyridinylazo)-2-naphthaleno (PAN) dissolved from the effervescence tablet to form a stable complex with Ni2+, and the extractant was uniformly dispersed in the sample solution under the action of CO2 and fully in contact with Ni-PAN, which enabled efficient extraction of Ni2+. The color changes of the extraction phase were captured by smartphone, then a quantitative relationship between the concentrations of Ni2+ and color intensity of images captured using a smartphone was established by customized applet WASDIC, which realized quantitative analysis of Ni2+ in different samples. Under optimal conditions, the enhancement factor (EF) of the proposed method was 65.1, the limit of detection (LOD) and limit of quantification (LOQ) were 1.69 and 5.64 µg L-1, respectively. The developed method was successfully applied to the detection of trace Ni2+ in the environmental samples and natural medicines. And the applicability of the method for use in field analysis was validated.

Risk assessment and source identification of soil heavy metals: a case study of farmland soil along a river in the southeast of a mining area in Southwest China.

To investigate the heavy metals (HMs) contamination of surface farmland soil along the river in the southeast of a mining area in southwest China and identify the contamination sources, 54 topsoil samples were collected and the concentrations of seven elements (Zn, Ni, Pb, Cu, Hg, Cr, and Co) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic fluorescence spectrometry (AFS). The geo-accumulation index ([Formula: see text]) and comprehensive potential ecological risk index ([Formula: see text]) were used for analysis to determine the pollution degree of HMs and the risk level of the study area. Meanwhile, the Positive Matrix Factorization (PMF) model was combined with a variety of statistical methods to determine the sources of HMs. To explore the influence of the river flowing through the mining area on the concentrations of HMs in the farmland soil, 15 water samples were collected and the concentrations of the above seven elements were determined. The results showed that the concentrations of Pb, Cu, and Zn in soil all exceeded the risk screening value, and Pb in soil of some sampling sites exceeded control value of "Agricultural Land Soil Pollution Risk Control Standard".[Formula: see text] showed that Pb was heavily contaminated, while Cu and Zn were moderately contaminated. RI showed that the study area was at moderate risk. PMF and various statistical methods showed that the main source of HMs was the industrial source. In the short term, the river flowing through the mine has no significant influence on the concentration of HMs in the soil. The results provide a reference for the local government to control contamination and identify the sources of HMs.

A Parallel Framework for Streaming Dimensionality Reduction.

The visualization of streaming high-dimensional data often needs to consider the speed in dimensionality reduction algorithms, the quality of visualized data patterns, and the stability of view graphs that usually change over time with new data. Existing methods of streaming high-dimensional data visualization primarily line up essential modules in a serial manner and often face challenges in satisfying all these design considerations. In this research, we propose a novel parallel framework for streaming high-dimensional data visualization to achieve high data processing speed, high quality in data patterns, and good stability in visual presentations. This framework arranges all essential modules in parallel to mitigate the delays caused by module waiting in serial setups. In addition, to facilitate the parallel pipeline, we redesign these modules with a parametric non-linear embedding method for new data embedding, an incremental learning method for online embedding function updating, and a hybrid strategy for optimized embedding updating. We also improve the coordination mechanism among these modules. Our experiments show that our method has advantages in embedding speed, quality, and stability over other existing methods to visualize streaming high-dimensional data.

Heavy metals distribution characteristics, source analysis, and risk evaluation of soils around mines, quarries, and other special areas in a region of northwestern Yunnan, China.

In this study, based on the assessment of soil heavy metals (HMs) pollution using relevant indices, a comprehensive approach combined network environ analysis (NEA), human health risk assessment (HHRA) method and positive definite matrix factor (PMF) model to quantify the risks among ecological communities in a special environment around mining area in northwest Yunnan, calculated the risk to human health caused by HMs in soil, and analyzed the pollution sources of HMs. The integrated risks for soil microorganisms, vegetations, herbivores, and carnivores were 2.336, 0.876, 0.114, and 0.082, respectively, indicating that soil microorganisms were the largest risk receptors. The total hazard indexes (HIT) for males, females, and children were 0.542, 0.591, and 1.970, respectively, revealing a relatively high and non-negligible non-carcinogenic risks (NCR) for children. The total cancer risks (TCR) for both females and children exceeded 1.00E-04, indicating that soil HMs posed carcinogenic risks (CR) to them. Comparatively, Pb was the high-risk metal, accounting for 53.76%, 57.90%, and 68.09% of HIT in males, females, and children, respectively. PMF analysis yielded five sources of pollution, F1 (industry), F2 (agriculture), F3 (domesticity), F4 (nature), and F5 (traffic).

Shoulder vibratory exercises improves shoulder external rotation muscle strength and shoulder function: Randomized comparison trial.

BACKGROUND: Based on electromyography measurements, shoulder vibratory exercises efficiently stimulate shoulder muscles activity. Yet very few studies have supported that shoulder vibratory exercises increased shoulder muscles strength and function, and the noninferiority compared with conventional elastic resistance exercises remains unknown. OBJECTIVE: This study investigated the effect of vibratory exercises versus conventional elastic resistance exercises with elastic bands on shoulder external rotation muscles strength and functional performance in young adults. METHODS: 26 young adults (7 males and 19 females, with age 23.89 ± 3.02) were recruited and randomly allocated to shoulder vibratory exercises with FLEXI-BAR (FLEXI-BAR group) or conventional resistance exercises with elastic band (TheraBand group) for 3 times/week, 4 weeks totally. Shoulder external rotator muscles strength test and Underkofler softball distance throw test (USDTT) were performed before and after the training period. RESULTS: After 4 weeks training, shoulder external rotator muscles strength increased 22.25 ± 15.06 N (P= 0.004, effect size = 1.48) within FLEXI-BAR group and 22.81 ± 14.94 N (P= 0.007, effect size = 1.53) within TheraBand group. There were no statistically significant differences between groups in the three muscle strength tests (P> 0.65). Regarding shoulder function, FLEXI-BAR exercises increased the throw distance 0.81 ± 0.92 meters in USDTT (P= 0.041, effect size = 0.88) while TheraBand exercise did not (P= 0.284), yet there was no statistically significant between group effects (P= 0.608). CONCLUSIONS: These findings suggest that shoulder vibratory exercises can improve shoulder muscles strength in young adults and can be a useful alternative to the conventional elastic resistance exercises to improve the shoulder muscles strength and function. This provides therapists with more options in terms of choosing training equipment for rehabilitation programs.

[Effect of acupuncture on protein kinase R-like endoplasmic reticulum kinase/eukaryotic translation initiation factor 2α signaling pathway in hippocampus of rats with post-traumatic stress disorder].

OBJECTIVE: To observe the effect of acupuncture on the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α) signaling pathway in the hippocampus of rats with post-traumatic stress disorder (PTSD), so as to explore the underlying mechanism of acupuncture in treating PTSD. METHODS: Twenty-eight SD rats were randomly divided into normal, model, acupuncture and sertraline groups, with 7 rats in each group. The PTSD model was established by single prolonged stress method. The next day after modeling, acupuncture was applied to "Baihui" (GV20) and "Dazhui" (GV14) of rats in the acupuncture group for 10 min, once a day for 7 days. Sertraline (10 mg/kg) was given by gavage to rats of the sertraline group daily for 7 days. The behavioral changes of rats were detected by elevated cross maze experiment and new object recognition experiment. The expression levels of PERK,phosphorylated(p)-PERK, eIF2α, p-eIF2α and activating transcription factor 4 (ATF4) proteins in hippocampus were detected by Western blot. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. RESULTS: Compared with the normal group, the percentage of times and retention time of entering the open arm of the elevated cross maze experiment, and new object recognition index were significantly decreased (P<0.01); the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly increased (P<0.05) of rats in the model group. Compared with the model group, the percentage of times and retention time of entering the open arm, and new object recognition index were significantly increased (P<0.05，P<0.01), the expression levels of p-PERK, p-eIF2α and ATF4 proteins in hippocampus were significantly decreased (P<0.05, P<0.01) of rats in the acupuncture and sertraline groups; the expression level of eIF2α protein was significantly decreased (P<0.05) in the sertraline group. Hippocampal neurons in the model group were damaged, the rough endoplasmic reticulum showed severe dilation, the mitochondrial cristae showed reduction or mild cavitation; compared with the model group, hippocampal neurons structural damage and the rough endoplasmic reticulum dilation were alleviated， and only some of the mitochondrial cristae decreased in the acupuncture and sertraline groups. CONCLUSION: Acupuncture can alleviate the anxiety behavior as well as the recognition and memory ability of PTSD rats, and its mechanism may be related to the inhibition of hippocampus PERK/eIF2α signaling pathway and the reduction of hippocampal neuron damage caused by endoplasmic reticulum stress.

Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression in macrophages by activating NF-κB pathway, and ITA produced by ACOD1 inhibits TET DNA dioxygenases to dampen the expression of inflammatory genes and the infiltration of CD8+ T cells into tumor sites. Deletion of Irg1 in mice suppresses the growth of multiple tumor types and enhances the efficacy of anti-PD-(L)1 immunotherapy. Our study provides a proof of concept that ACOD1 is a potential target for immune-oncology drugs and IRG1-deficient macrophages represent a potent cell therapy strategy for cancer treatment even in pancreatic tumors that are resistant to T cell-based immunotherapy.

The immunometabolite itaconate stimulates OXGR1 to promote mucociliary clearance during the pulmonary innate immune response.

Pathogens and inflammatory conditions rapidly induce the expression of immune-responsive gene 1 (IRG1) in cells of myeloid lineage. IRG1 encodes an aconitate decarboxylase (ACOD1) that produces the immunomodulatory metabolite itaconate (ITA). In addition to rapid intracellular accumulation, ITA is also secreted from the cell, but whether secreted ITA functions as a signaling molecule is unclear. Here, we identified ITA as an orthosteric agonist of the GPCR OXGR1, with an EC50 of approximately 0.3 mM, which was in the same range as the physiological concentration of extracellular ITA upon macrophage activation. ITA activated OXGR1 to induce Ca2+ mobilization, ERK phosphorylation, and endocytosis of the receptor. In a mouse model of pulmonary infection with bacterial Pseudomonas aeruginosa, ITA stimulated Oxgr1-dependent mucus secretion and transport in respiratory epithelium, the primary innate defense mechanism of the airway. Our study thus identifies ITA as a bona fide ligand for OXGR1 and the ITA/OXGR1 paracrine signaling pathway during the pulmonary innate immune response.

Recyclable ferroferric oxide@titanium dioxide@molybdenum disulfide with enhanced enzyme-like activity under visible light for effectively inhibiting the growth of drug-resistant bacteria in sewage.

With the development of social industry and the increase in domestic sewage discharge, pathogenic bacterial contamination in water has become a serious health and environmental problem. It is important to design sewage treatment reagents with effective pathogenic bacterial removal and recyclability. In this work, we developed a nanocomposite, Fe3O4@TiO2@MoS2, with once-for-all effects of photocatalytic, magnetic, and peroxidase-like activities for solving the above-mentioned problems. The loading of MoS2 may cause the band gap of Fe3O4@TiO2 to decrease from 3.11 eV to 2.85 eV, demonstrating increased photocatalytic activity under visible light, based on the synergistic impact of Fe3O4@TiO2 and MoS2. In return, the peroxidase-like activity of Fe3O4@TiO2@MoS2 was significantly higher than that of Fe3O4 and MoS2 alone, resulting in the generation of more hydroxyl radicals (˙OH) for combating the drug-resistant broad-spectrum ß-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus. The antibacterial mechanism study showed that Fe3O4@TiO2@MoS2 could effectively inhibit bacterial growth by destroying the bacterial biofilm and genome via the peroxidase-like activity as well as photocatalytic activity. In addition, Fe3O4@TiO2@MoS2 has excellent paramagnetic properties, which can achieve magnetic recovery after wastewater treatment. Even after three times of recycling, its antibacterial effect can remain above 98.8%.

Development of Uveal Melanoma-Specific Aptamer for Potential Biomarker Discovery and Targeted Drug Delivery.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. However, challenges in early diagnosis, high risk of liver metastasis, and lack of effective targeted therapy lead to poor prognosis and high mortality of UM. Therefore, generating an effective molecular tool for UM diagnosis and targeted treatment is of great significance. In this study, a UM-specific DNA aptamer, PZ-1, was successfully developed, which could specifically distinguish molecular differences between UM cells and noncancerous cells with nanomolar-range affinity and presented excellent recognition ability for UM in vivo and clinical UM tissues. Subsequently, the binding target of PZ-1 on UM cells was identified as JUP (junction plakoglobin) protein, which held great potential as a biomarker and therapeutic target for UM. Meanwhile, the strong stability and internalization capacity of PZ-1 were also determined, and a UM-specific aptamer-guided "nanoship" was engineered to load and selectively release doxorubicin (Dox) to targeted UM cells, with lower toxicity to nontumor cells. Taken together, the UM-specific aptamer PZ-1 could serve as a molecular tool to discover the potential biomarker for UM and to achieve the targeted therapy of UM.

Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein.

Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.

Microenvironment-Adaptive Nanozyme for Accelerating Drug-Resistant Bacteria-Infected Wound Healing.

Reactive oxygen species (ROS) are favorable for antibacterial infection but their overproduction results in serious inflammatory response and aggravates the hypoxic state of the wound tissue, which is detrimental to healing stages of proliferation and remodeling. Here, an atomic-dispersion Fe-doped oxygen-deficient molybdenum oxide MoO3- X (ADFM) bifunctional nanozyme, featuring implanted peroxidase-like and enhanced catalase-like activity, is developed for decomposing H2 O2 into strongly oxidizing hydroxyl radicals (•OH) for prevention of bacterial infection and into plentiful O2 for healing stages. Therein, the introduction of Fe into MoO3- X primarily produces an asymmetric electron density difference by elongating the bond length between metal atoms, synchronously stabilizing adsorption of •OH and weakening the adsorption of O2 . ADFM also shows unimaginably high aqueous dispersity and pH-adaptive ROS regulation in the wound microenvironment, both of which are favorable for ADFM to fully exert enzyme-like activity for timely antibacterial and efficient wound-healing action. ADFM thus achieves efficient healing of drug-resistant bacteria-infected wounds in vivo, at an ultralow dosage of 30 µg mL-1 against 106 CFU mL-1 extended spectrum ß-lactamases-producing Escherichia coli, exhibiting a wound-healing efficiency of ≈10 mm2 per day, which sets a benchmark among these noble-metal-free nanozyme-based wound-healing agents.

A novel predictive model for poor in-hospital outcomes in patients with acute kidney injury after cardiac surgery.

OBJECTIVE: Patients with cardiac surgery-associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery-associated acute kidney injury. METHODS: A total of 196 patients diagnosed with cardiac surgery-associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52). RESULTS: A change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer-Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine. CONCLUSIONS: We developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery-associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery-associated acute kidney injury.

Gestational Exposure to Cyfluthrin through Endoplasmic Reticulum (ER) Stress-Mediated PERK Signaling Pathway Impairs Placental Development.

Cyfluthrin, a typical type II pyrethroid pesticide, is widely used in house hygiene and agricultural pest control. Several epidemiological investigations have found that maternal pyrethroid exposure is connected to adverse pregnancy outcomes. However, the underlying mechanisms remain to be elucidated. Thus, we evaluated the effect of cyfluthrin exposure during pregnancy on placenta development in vivo. In the current study, Pregnant SD rats were randomly divided into four groups and administered 6.25, 12.5, and 25 mg/kg body weight cyfluthrin or an equivalent volume of corn oil by gavage from GD0 to GD19. The results have shown that gestational exposure to cyfluthrin exerted no effect on the fetal birth defect, survival to PND4, or fetal resorption and death. However, live fetuses and implantation sites significantly decreased in the high-dose cyfluthrin-treated group. Moreover, a significant reduction in placenta weight and diameter was observed in rats. Correspondingly, the fetal weight and crown-rump length from dams exposed to cyfluthrin were reduced. Cyfluthrin-treat groups, the total area of the placenta, spongiotrophoblast area, and labyrinth area had abnormal changes. Meanwhile, the area of blood sinusoid and CD34-positive blood vessel numbers in the placenta were considerably reduced, as well as abnormal expression of placental pro-angiogenic and anti-angiogenic factors in dams exposed to cyfluthrin. Further observation by transmission electron microscopy revealed significant changes in the ultrastructure of the medium-dose and high-dose groups. Additional experiments showed gestational exposure to cyfluthrin inhibited proliferation and induced apoptosis of placentas, as decreased PCNA-positive cells and increased TUNEL-positive cells. Furthermore, western blot and qPCR analysis revealed that gestational exposure to medium-dose and high-dose cyfluthrin increased the expression of GRP78, and three downstream mRNA and proteins (p-eIF2α, ATF4, and CHOP) of the PERK signaling, indicating that endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP signaling pathway in rat placentas was activated. Our study demonstrated that gestational exposure to cyfluthrin leads to placental developmental disorder, which might be associated with ER stress-mediated PERK signaling pathway.