Integration of single-cell and RNA-seq data to explore the role of focal adhesion-related genes in osteoporosis.

Integrin-based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single-cell RNA sequencing and RNA-sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors-hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti-RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA-seq and RNA-seq analyses, which might supply a new insight for the treatment and evaluation of OP.

Intelligent Identification of Cerebrospinal Fluid for the Diagnosis of Parkinson's Disease.

Cerebrospinal fluid (CSF) biomarkers are more sensitive than the Movement Disorder Society (MDS) criteria for detecting prodromal Parkinson's disease (PD). Early detection of PD provides the best chance for successful implementation of disease-modifying treatments, making it crucial to effectively identify CSF extracted from PD patients or normal individuals. In this study, an intelligent sensor array was built by using three metal-organic frameworks (MOFs) that exhibited varying catalytic kinetics after reacting with potential protein markers. Machine learning algorithms were used to process fingerprint response patterns, allowing for qualitative and quantitative assessment of the proteins. The results were robust and capable of discriminating between PD and non-PD patients via CSF detection. The k-nearest neighbor regression algorithm was used to predict MDS scores with a minimum mean square error of 38.88. The intelligent MOF sensor array is expected to promote the detection of CSF biomarkers due to its ability to identify multiple targets and could be used in conjunction with MDS criteria and other techniques to diagnose PD more sensitively and selectively.

Dietary α-Ketoglutarate Alleviates Escherichia coli LPS-Induced Intestinal Barrier Injury by Modulating the Endoplasmic Reticulum-Mitochondrial System Pathway in Piglets.

BACKGROUND: α-Ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health. OBJECTIVES: This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum (MAM) membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum (ER) stress in a piglet model. METHODS: Twenty-four piglets were subjected to a 2 × 2 factorial design with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 d of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into 4 treatment groups [control (CON) group: basal diet + saline; LPS group: basal diet +LPS; AKG group: AKG diet + saline; and AKG_LPS group: AKG + LPS], each consisting of 6 piglets. RESULTS: The results demonstrated that compared with the CON group, AKG enhanced jejunal morphology, antioxidant capacity, and the messenger RNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. In addition, fewer disorders in the ER-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), ER stress [activating transcription factor (ATF) 4, ATF 6, CCAAT/enhancer binding protein homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, and protein kinase R-like ER kinase], and MAM membranes [mitofusin (Mfn)-1, Mfn-2, GRP 75, and voltage-dependent anion channel-1]. CONCLUSIONS: Dietary AKG can prevent mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorder, ultimately alleviating LPS-induced intestinal damage in piglets.

Association of intra-shift nap duration with heart rate variability in medical night shift workers.

Napping during night shifts effectively reduces disease risk and improves work performance, but few studies have investigated the association between napping and physiological changes, particularly in off-duty daily lives. Changes in the autonomic nervous system precede diseases like cardiovascular disease, diabetes, and obesity. Heart rate variability is a good indicator of autonomic nervous system. This study aimed to investigate the link between night shift nap durations and heart rate variability indices in the daily lives of medical workers. As indicators of chronic and long-term alterations, the circadian patterns of heart rate variability indices were evaluated. We recruited 146 medical workers with regular night shifts and divided them into four groups based on their self-reported nap durations. Heart rate variability circadian parameters (midline-estimating statistic of rhythm, amplitude, and acrophase) were obtained by obtaining 24-h electrocardiogram on a day without night shifts, plotting the data of the heart rate variability indices as a function of time, and fitting them into periodic cosine curves. Using clinical scales, depression, anxiety, stress, fatigue, and sleepiness were assessed. Linear regression analysis revealed a positive relationship between 61-120-min naps and 24-h, daytime, and night-time heart rate variability indices, and the parasympathetic activity oscillation amplitude (indexed by high-frequency power, the square root of the mean of the sum of squares of differences between adjacent normal intervals, standard deviation of short-term R-R-interval variability) within one circadian cycle. This study indicated that napping for 61-120 min during night shifts could benefit medical workers' health, providing physiological evidence to promote nap management.

Effects of chronotype on sleep, mood and cardiovascular circadian rhythms in rotating night shift medical workers.

PURPOSE: Whether chronotype affects the health outcomes of night shift work populations is unknown. This study aimed to assess the influence of different chronotypes in the rotating night shift population on sleep status, mood, blood pressure (BP), and heart rate variability (HRV), as well as the circadian rhythm of BP and HRV. METHODS: A total of 208 rotating night shift workers were included. All participants completed structured questionnaires to assess chronotype, mood and sleep status. During their daily lives outside of the night shift, they underwent 24-hour Holter electrocardiogram monitoring and 24-hour ambulatory blood pressure monitoring. Day-time and night-time BP and BP dipping were obtained. Day-time and night-time HRV values (SDNN, RMSSD, LF, HF, LF nu, SD1, SD2 and SD2/SD1) were calculated and fitted to the cosine period curve. Three circandian parameters (mesor, amplitude and acrophase) were extracted to quantify the circadian rhythm of the HRV indices. RESULTS: Among all three groups, E-type showed more fatigue and sleepiness. In addition, E-type showed blunted diastolic BP dipping. Notably, E-type showed association with higher RMSSD, LF, HF and SD1 in the night time, and higher mesors of RMSSD and LF and amplitude of SD2/SD1 in circadian analysis. CONCLUSION: Chronotype is a factor affecting fatigue, sleepiness and cardiovascular circadian rhythms of rotating night shift workers. Chronotype should be taken into consideration for managing night-shift rotation to promote occupational health.

Safety and efficacy of daratumumab in Chinese patients with relapsed or refractory multiple myeloma: a phase 1, dose-escalation study (MMY1003).

Daratumumab monotherapy demonstrated favorable safety and efficacy in relapsed/refractory multiple myeloma (RRMM) patients in the global phase 1/2 GEN501 and phase 2 SIRIUS studies. MMY1003 evaluated daratumumab monotherapy specifically in Chinese patients with RRMM. This 3-part, open-label, phase 1, dose-escalation study included patients with ≥ 2 prior lines of therapy. Part 3 included patients who had received a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and experienced disease progression on their last regimen. Patients received intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 and 16 mg/kg in parts 2 + 3. Primary endpoints were dose-limiting toxicity (DLT; part 1), pharmacokinetics (parts 1 + 2), and adverse events (AEs). Fifty patients enrolled. The first 3 patients in part 1 received daratumumab 8 mg/kg; remaining patients in parts 1-3 received daratumumab 16 mg/kg. In the daratumumab 16 mg/kg group (n = 47), patients received a median of 4 prior lines of therapy; 32% were refractory to a PI and IMiD, and 79% were refractory to their last prior therapy. No DLTs occurred. Thirty-six (77%) patients reported grade 3/4 treatment-emergent AEs. Thirteen (28%) patients experienced infusion-related reactions. At an 18.5-month median follow-up, overall response rate was 43%. Median progression-free survival (PFS) and overall survival (OS) were 6.7 months and not reached, respectively; 12-month PFS and OS rates were 35% and 70%. Pharmacokinetic results (n = 22) were consistent with other studies. Safety, pharmacokinetics, and efficacy of daratumumab monotherapy were confirmed in Chinese patients with RRMM. This trial is registered on ClinicalTrials.gov (NCT02852837).

Primary cardiac composite hemangioendothelioma with calcification mimicking a right atrial myxoma: A rare entity.

Composite hemangioendothelioma (CHE) is a rare vascular tumor which shows varying combination of benign, low-grade, and malignant vascular components on pathology. CHE is usually located on the surface of the dermis and subcutaneous tissue of the extremities. We report an unusual case of CHE in the heart.

Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR-296-3p/PTEN axis.

Circular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain-of-function and loss-of-function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR-296-3p and miR-296-3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno-associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)-induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR-296-3p and regulating the miR-296-3p-PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM-induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR-296-3p-PTEN pathway. It provides a potential target for developing effective interventions in treating OA.

Tumour necrosis factor-α promotes BMHSC differentiation by increasing P2X7 receptor in oestrogen-deficient osteoporosis.

The exact mechanism of tumour necrosis factor α (TNF-α) promoting osteoclast differentiation is not completely clear. A variety of P2 purine receptor subtypes have been confirmed to be widely involved in bone metabolism. Thus, the purpose of this study was to explore whether P2 receptor is involved in the differentiation of osteoclasts. Mouse bone marrow haematopoietic stem cells (BMHSCs) were co-cultured with TNF-α to explore the effect of TNF-α on osteoclast differentiation and bone resorption capacity in vitro, and changes in the P2 receptor were detected at the same time. The P2 receptor was silenced and overexpressed to explore the effect on differentiation of BMHSCs into osteoclasts. In an in vivo experiment, the animal model of PMOP was established in ovariectomized mice, and anti-TNF-α intervention was used to detect the ability of BMHCs to differentiate into osteoclasts as well as the expression of the P2 receptor. It was confirmed in vitro that TNF-α at a concentration of 20 ng/mL up-regulated the P2X7 receptor of BMHSCs through the PI3k/Akt signalling pathway, promoted BMHSCs to differentiate into a large number of osteoclasts and enhanced bone resorption. In vivo experiments showed that more P2X7 receptor positive osteoclasts were produced in postmenopausal osteoporotic mice. Anti-TNF-α could significantly delay the progression of PMOP by inhibiting the production of osteoclasts. Overall, our results revealed a novel function of the P2X7 receptor and suggested that suppressing the P2X7 receptor may be an effective strategy to delay bone formation in oestrogen deficiency-induced osteoporosis.

Fluorescence "on-off-on" Assay of Copper Ions and EDTA Using Amino-Functionalized Graphene Quantum Dots.

Copper is an important trace element involved in several physiological processes. The deficiency or excess of Cu in the human body may cause some serious diseases. EDTA has been widely employed in many industry fields owing to its excellent chelating ability. The poor biodegradability of EDTA makes itself a persistent substance in the natural environment. This work provided a fluorescence "on-off-on" strategy for the sequential determination of trace Cu2+ and EDTA. Amino-functionalized graphene quantum dots (afGQDs) were synthetized via the thermal pyrolysis of citric acid. Fluorescence resonance energy transfer (FRET) between afGQDs and 1-(2-pyridylazo)-2-naphthol (PAN) effectively quenched the fluorescence of this carbon-based nanomaterial. The generation of the Cu2+-PAN complex caused the increased FRET efficiency and the further fluorescence decline. The change of the fluorescence intensity sensitively responded to copper ions. The linear range and the limit of detection (LOD) were 1 nM-10 µM and 0.87 nM, respectively. EDTA could decompose the Cu2+-PAN complex and liberate PAN, which weakened the FRET efficiency and led to the fluorescence recovery. The increasing degree of the fluorescence intensity was closely related to EDTA within a concentration range from 10 nM to 10 µM with a LOD at 4 nM. Copper ions in the water and human serum samples and EDTA in the trypsin-EDTA sample were successfully detected based on the proposed fluorescence method.

circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR-127-5p.

Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1ß)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL-1ß-treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.

Ultrasensitive determination of mercury ions using a glassy carbon electrode modified with nanocomposites consisting of conductive polymer and amino-functionalized graphene quantum dots.

A one-pot method based on cyclic voltammetric scan was used to fabricate a glassy carbon electrode modified with nanocomposites consisting of poly(thionine) and amino-functionalized graphene quantum dots (afGQDs). Under near-neutral conditions, the dye polymer was effectively oxidized by hydroxyl radicals (·OH) that were derived from the copper-catalyzed Fenton-like reaction, and the cathodic peak current on the modified electrode greatly increased. The reaction of Cu2+ with thiourea (TU) and the generation of a complex, CuTU2+, led to the decrease of Cu2+/Cu+ species, which inhibited the Fenton-like reaction and reduced the electrochemical response change. Due to a displacement reaction, the addition of Hg2+ into the H2O2-Cu2+-TU system resulted in the release of cuprous ions that benefited the Fenton-like reaction. Under the following optimal conditions: 6 mg mL-1 afGQDs and the 25-cycle potential cycling for the fabrication of the modified electrode, pH 6.5, and the [Formula: see text] ratio of 1.0, the increasing extent of the cathodic peak current exhibited a good linear response to the logarithm of the Hg2+ concentration in the range of 1 pM-1 µM with a detection limit of 0.6 pM. Mercury ions in a water sample were determined with good recovery, ranging from 97 to 103%. The investigation on the uptake of Hg2+ into human vascular endothelial cells, HUVEC, shows that the cells incubated in the high-concentration glucose medium absorbed more mercury ions than HUVEC incubated in the normal medium. As a result, Hg2+ could lead to the greater damage to the former. Graphical abstract.

Is selective nerve root block necessary for learning percutaneous endoscopic lumbar discectomy: a comparative study using a cumulative summation test for learning curve.

PURPOSE: The aim of this study was to investigate the effect of lumbar spine selective nerve root block (SNRB) experience on the learning efficiency of percutaneous endoscopic lumbar discectomy (PELD) for junior trainees. METHODS: A total of 480 patients undergoing single-level PELD performed by eight junior trainees were included. The trainees were divided into two groups based on whether they had previous SNRB experience (group A, yes; group B, no). Surgical proficiency was defined as total operation time less than 65 minutes and cumulative radiation exposure time no more than 40 seconds. The learning curve was analyzed by cumulative summation (CUSUM) test. Clinical evaluations included Macnab classification, visual analog scale (VAS)-low back score, VAS-leg score, and Oswestry Disability Index (ODI). Follow-up information at 12 months was also obtained. RESULTS: Integral number of cases before achieving an acceptable surgical level in group A (47.75 ± 2.50 cases) was significantly smaller than that in group B (56.50 ± 1.29 cases, p < 0.05), along with less accumulated failure (18.75 ± 0.96 cases vs. 25.50 ± 1.75 cases, p < 0.05). The two groups were comparable in clinical outcomes. Forty-seven cases of complications were observed, with 17 in group A and 30 in group B (p < 0.05). CONCLUSION: Previous experience of SNRB improved the performance of PELD with shorter operation time and less radiation exposure. SNRB practice may reduce the complication rate without a significant effect on the recurrence of symptoms and reoperation.

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

MAGI1 inhibits migration and invasion via blocking MAPK/ERK signaling pathway in gastric cancer.

OBJECTIVE: To explore the association of membrane-associated guanylate kinase inverted 1 (MAGI1) with gastric cancer (GC) and the related molecular mechanisms. METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were utilized to measure the MAGI1 expression level in GC tissues. Quantitative real-time PCR and Western blotting were used to ensure the MAGI1 expression in GC cell lines. Small hairpin RNA (shRNA) was applied for knockdown of endogenous MAGI1 in GC cells. MTT assay and colony formation assay, scratch wounding migration assay and transwell chamber migration assay, as well as transwell chamber invasion assay were employed respectively to investigate the GC cell proliferation, migration and invasion in MAGI1-knockdown and control GC cells. The potential molecular mechanism mediated by MAGI1 was studied using Western blotting and RT- PCR. RESULTS: RT-PCR and IHC verified MAGI1 was frequently expressed in matched adjacent noncancerous mucosa compared with GC tissues and the expression of MAGI1 was related to clinical pathological parameters. Functional assays indicated that MAGI1 knockdown significantly promoted GC cell migration and invasion. Further mechanism investigation demonstrated that one pathway of MAGI1 inhibiting migration and invasion was mainly by altering the expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT)-related molecules via inhibiting MAPK/ERK signaling pathway. CONCLUSIONS: MAGI1 was associated with GC clinical pathological parameters and acted as a tumor suppressor via inhibiting of MAPK/ERK signaling pathway in GC.

IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions.

BACKGROUND/AIMS: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. METHODS: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. RESULTS: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. CONCLUSION: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

Impact of stress hyperglycemia ratio on mortality in patients with cardiac arrest: insight from American MIMIC-IV database.

Background: Stress hyperglycemia ratio (SHR) has shown a predominant correlation with transient adverse events in critically ill patients. However, there remains a gap in comprehensive research regarding the association between SHR and mortality among patients experiencing cardiac arrest and admitted to the intensive care unit (ICU). Methods: A total of 535 patients with their initial ICU admission suffered cardiac arrest, according to the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were stratified into four categories based on quantiles of SHR. Multivariable Cox regression models were used to evaluate the association SHR and mortality. The association between SHR and mortality was assessed using multivariable Cox regression models. Subgroup analyses were conducted to determine whether SHR influenced ICU, 1-year, and long-term all-cause mortality in subgroups stratified according to diabetes status. Results: Patients with higher SHR, when compared to the reference quartile 1 group, exhibited a greater risk of ICU mortality (adjusted hazard ratio [aHR] = 3.029; 95% CI: 1.802-5.090), 1-year mortality (aHR = 3.057; 95% CI: 1.885-4.958), and long-term mortality (aHR = 3.183; 95% CI: 2.020-5.015). This association was particularly noteworthy among patients without diabetes, as indicated by subgroup analysis. Conclusion: Elevated SHR was notably associated with heightened risks of ICU, 1-year, and long-term all-cause mortality among cardiac arrest patients. These findings underscore the importance of considering SHR as a potential prognostic factor in the critical care management of cardiac arrest patients, warranting further investigation and clinical attention.

Alpha-ketoglutaric acid attenuates oxidative stress and modulates mitochondrial dynamics and autophagy of spleen in a piglet model of lipopolysaccharide-induced sepsis.

Alpha-ketoglutaric acid (2-ketoglutaric acid or 2-oxoglutaric acid, AKG), a crucial intermediate in the tricarboxylic acid cycle, is pivotal in animal antioxidative process. The purpose of this study was to investigate whether AKG has the efficacy to mitigate spleen oxidative stress in lipopolysaccharide (LPS)-induced sepsis piglets through the modulation of mitochondrial dynamics and autophagy. Utilizing a 2 × 2 factorial design, the study encompassed 24 piglets subjected to varying diets (basal or 1% AKG) and immune stimulations (saline or LPS) over 21 days. Subsequently, they were injected intraperitoneally with either LPS or saline solution. The results showed that LPS decreased antioxidant capacity, whereas AKG supplementation increased antioxidant activities compared to control group. LPS elevated mitochondrial fission factor, mitochondrial elongation factor 1, mitochondrial elongation factor 2, dynamin-related protein 1, voltage-dependent anion channel 1, and fission 1 mRNA abundance, but reduced mRNA abundance of mitofusin 1, mitofusin 2, and optic atrophy 1 compared to controls. LPS elevated mRNA abundance of autophagy related protein 5, autophagy related protein 7, P62, Beclin1, and interleukin-1ß mRNA abundance compared to controls. However, AKG supplementation mitigated these effects induced by LPS. Additionally, AKG intake was associated with lower protein expressions of microtubule-associated protein light chain 3, Parkin, and PTEN-induced putative kinase 1 compared to LPS-challenged piglets. These results suggested that AKG could alleviate spleen oxidative stress caused by LPS by regulating mitochondrial dynamics and autophagy.

Sleep-phasic heart rate variability predicts stress severity: Building a machine learning-based stress prediction model.

We propose a novel approach for predicting stress severity by measuring sleep phasic heart rate variability (HRV) using a smart device. This device can potentially be applied for stress self-screening in large populations. Using a Holter electrocardiogram (ECG) and a Huawei smart device, we conducted 24-h dual recordings of 159 medical workers working regular shifts. Based on photoplethysmography (PPG) and accelerometer signals acquired by the Huawei smart device, we sorted episodes of cyclic alternating pattern (CAP; unstable sleep), non-cyclic alternating pattern (NCAP; stable sleep), wakefulness, and rapid eye movement (REM) sleep based on cardiopulmonary coupling (CPC) algorithms. We further calculated the HRV indices during NCAP, CAP and REM sleep episodes using both the Holter ECG and smart-device PPG signals. We later developed a machine learning model to predict stress severity based only on the smart device data obtained from the participants along with a clinical evaluation of emotion and stress conditions. Sleep phasic HRV indices predict individual stress severity with better performance in CAP or REM sleep than in NCAP. Using the smart device data only, the optimal machine learning-based stress prediction model exhibited accuracy of 80.3 %, sensitivity 87.2 %, and 63.9 % for specificity. Sleep phasic heart rate variability can be accurately evaluated using a smart device and subsequently can be used for stress predication.

The Potential of Spent Coffee Grounds @ MOFs Composite Catalyst in Efficient Activation of PMS to Remove the Tetracycline Hydrochloride from an Aqueous Solution.

The efficient removal of Tetracycline Hydrochloride (TC) from wastewater, which is a difficult process, has attracted increasing attention. Aiming to synchronously achieve the goal of natural waste utilization and PMS activation, we have combined the MOFs material with waste coffee grounds (CG). The catalytic activity of the CG@ZIF-67 composite in the TC removal process was thoroughly evaluated, demonstrating that the TC removal rate could reach 96.3% within 30 min at CG@ZIF-67 composite dosage of 100 mg/L, PMS concertation of 1.0 mM, unadjusted pH 6.2, and contact temperate of 293.15 K. The 1O2 and ·SO4- in the CG@ZIF-67/PMS/TC system would play the crucial role in the TC degradation process, with 1O2 acting as the primary ROS. The oxygen-containing functional groups and graphite N on the surface of CG@ZIF-67 composite would play a major role in efficiently activating PMS and correspondingly degrading TC. In addition, the CG@ZIF-67/PMS/TC system could withstand a wide pH range (3-11). The application of CG in preparing MOF-based composites will provide a new method of removing emerging pollutants from an aqueous solution.