Lactate contributes to remote ischemic preconditioning-mediated protection against myocardial ischemia reperfusion injury by facilitating autophagy via AMPK-mTOR-TFEB-CX43 axis.

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 (MCT1) inhibitor and 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia reoxygenation (H/R) model, lactate markedly mitigated H/R-induced cell damage in H9c2 cells. Meanwhile, further studies suggested that lactate contributed to RIPC rescuing I/R-induced autophagy deficiency by promoting TFEB translocation to the nucleus through activating the AMPK-mTOR pathway without influencing the PI3K-Akt pathway, thus reducing cardiomyocytes damage. Interestingly, we also found that lactate upregulated the mRNA and protein expression of CX43 by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested lactate facilitated CX43-regulated autophagy via AMPK-mTOR-TFEB signaling pathway. Collectively, our research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via AMPK-mTOR-TFEB-CX43 axis.

Remotely sensed estimates of long-term biochemical oxygen demand over Hong Kong marine waters using machine learning enhanced by imbalanced label optimisation.

In many coastal cities around the world, continuing water degradation threatens the living environment of humans and aquatic organisms. To assess and control the water pollution situation, this study estimated the Biochemical Oxygen Demand (BOD) concentration of Hong Kong's marine waters using remote sensing and an improved machine learning (ML) method. The scheme was derived from four ML algorithms (RBF, SVR, RF, XGB) and calibrated using a large amount (N > 1000) of in-situ BOD5 data. Based on labeled datasets with different preprocessing, i.e., the original BOD5, the log10(BOD5), and label distribution smoothing (LDS), three types of models were trained and evaluated. The results highlight the superior potential of the LDS-based model to improve BOD5 estimate by dealing with imbalanced training dataset. Additionally, XGB and RF outperformed RBF and SVR when the model was developed using log10(BOD5) or LDS(BOD5). Over two decades, the BOD5 concentration of Hong Kong marine waters in the autumn (Sep. to Nov.) shows a downward trend, with significant decreases in Deep Bay, Western Buffer, Victoria Harbour, Eastern Buffer, Junk Bay, Port Shelter, and the Tolo Harbour and Channel. Principal component analysis revealed that nutrient levels emerged as the predominant factor in Victoria Harbour and the interior of Deep Bay, while chlorophyll-related and physical parameters were dominant in Southern, Mirs Bay, Northwestern, and the outlet of Deep Bay. LDS provides a new perspective to improve ML-based water quality estimation by alleviating the imbalance in the labeled dataset. Overall, the remotely sensed BOD5 can offer insight into the spatial-temporal distribution of organic matter in Hong Kong coastal waters and valuable guidance for the pollution control.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.

Link Brain-Wide Projectome to Neuronal Dynamics in the Mouse Brain.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

Knowledge and attitude of spouses of puerperas towards breastfeeding.

OBJECTIVE: To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing spousal attitudes toward breastfeeding. METHODS: We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling. RESULTS: (1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 "Newborns should be fed on time, not on demand" (42.6%) and Item 5 "Breastfeeding can prevent infant rickets" (49.5%). (2) The average score of spouses' infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 "Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk" (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education [OR = 4.588, 95% CI (0.160 ∼ 3.598)] and those with a master's degree or above [OR = 18.278, 95% CI (3.471 ∼ 9.346)]. CONCLUSION: (1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas'spouses with degrees below master's level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.

Analysis of the correlation between general postpartum well-being and depression in primiparas: A cross-sectional study.

To investigate the status quo and influencing factors of general postpartum well-being in primiparas, analyze its correlation with postpartum depression, and provide a theoretical foundation for enhancing the postpartum well-being of primiparas. From the start of November 2021 to the end of December 2021, the General Information Questionnaire, General Well-Being Scale, and the Edinburgh Postpartum Depression Scale were used to survey primiparas in a tertiary hospital, and the correlation between general well-being and postpartum depression was analyzed. We surveyed a total of 225 primiparas. The average score for general well-being in primiparas was 77.84 ±â€…6.83, and the total score for postpartum depression was 9.11 ±â€…2.51. Confinement location, planned pregnancy, pregnancy complications, neonatal sex, medical expenses, etc, had statistically significant effects on the general well-being scores (P < .05), whereas per capita monthly income, pregnancy complications, maternal and infant care skills, and medical expenses had statistically significant effects on postpartum depression scores (P < .05). Postpartum depression scores were negatively correlated with general well-being, health anxiety, energy, sad or happy mood, relaxation, and tension. There is a negative correlation between the general well-being of primiparas and postpartum depression, suggesting that in clinical care, the focus should be on primiparas with pregnancy complications, and psychological counseling should be provided in advance to prevent postpartum depression and the resulting decrease in well-being.

Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma.

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC.

Preparation of a Single-Cell Suspension from Mouse Carotid Arteries for Single-Cell Sequencing.

Carotid arteries are major blood vessels in the neck that supply blood and oxygen to the brain, but carotid stenosis occurs when carotid arteries are clogged by plaque. Revealing the cellular composition of the carotid artery at the single-cell level is essential for treating carotid atherosclerosis. However, there is no ready-to-use protocol for the preparation of single-cell suspensions from carotid arteries. To obtain a suitable protocol for the dissociation of normal carotid arteries at the single-cell level with less damage to cells, we designed a two-step digestion method by integrating the digestion process of collagenase/DNase and trypsin. Acridine orange/propidium iodide (AO/PI) dual-fluorescence counting was used to detect cell viability and concentration, and it was found that the single-cell suspension satisfied the requirements for single-cell sequencing, with the viability of cells over 85% and a high cell concentration. After single-cell data processing, a median of ~2500 transcripts per cell were detected in each carotid artery cell. Notably, a variety of cell types of the normal carotid artery, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), and macrophages and dendritic cells (Mφ/DCs), were concurrently detectable. This protocol may be applied to prepare a single-cell suspension of blood vessels from other tissues with appropriate modifications.

Inflammatory cutaneous metastases originating from gastric cancer: A case report.

BACKGROUND: Cutaneous metastasis with gastric cancer (GC) origin is extremely rare and associated with poor prognosis. Nodular type is the most common type, while other forms are extremely rare. CASE SUMMARY: This study describes severe skin redness, swelling, pain, and fever in a 65-year-old man diagnosed with GC, whose left chest wall, left upper limb, and left back were mainly affected. Firstly, the patient was diagnosed with "lymphangitis" and treated to promote lymphatic return. However, the symptoms were constantly deteriorating, and skin thickening and scattered small nodules gradually appeared. Finally, the skin biopsy confirmed cutaneous metastases, and the patient died 7 d later. CONCLUSION: Our case highlights that cutaneous metastasis should be considered when skin lesions appear in patients with GC.

Open aneurysmorrhaphy for repair of a massive iliac vein aneurysm and review of the recent literature.

An iliac vein aneurysm is a rare vascular anomaly, scarcely reported in the vascular literature. We present the case of a 72-year-old man with a history of a remote heart transplant complicated by severe tricuspid regurgitation and traumatic abdominal injury, who was incidentally found to have a 10-cm right common iliac vein aneurysm. Because of the size and risk of rupture, we elected to treat him with surgical iliac vein aneurysmorrhaphy. His iliac venous diameter and flow continued to be stable at subsequent follow-up.

[Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION: Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Photoelectrochemical aptasensing of lincomycin based on a AgI-carboxylated multiwalled carbon nanotubes-BiOI Z-scheme heterojunction.

Lincomycin (LIN) is a common antibiotic that is widely used in animal husbandry and other fields, and the residual problem caused by its abuse has attracted widespread attention. Herein, a novel AgI-carboxylated multiwalled carbon nanotubes (cMWCNT)-BiOI Z-scheme heterojunction material was synthesized via a one-pot hydrothermal method, modified on a fluorine-doped tin oxide (FTO) electrode surface, and used for detecting LIN. The photocurrent on the AgI-cMWCNT-BiOI/FTO photoelectrode is 4.6 times that on the control AgI-BiOI/FTO photoelectrode. An amino-functionalized LIN aptamer was fixed on the AgI-cMWCNT-BiOI/FTO photoelectrode by the cross-linking reaction between chitosan and glutaraldehyde, and then Ru(NH3)63+ was electrostatically attached to the LIN aptamer to increase the photocurrent response to the LIN binding. When LIN binds competitively with Ru(NH3)63+ to the aptamer, the photocurrent signal can be quantitatively decreased. Under optimized conditions, the anodic photocurrent at 0 V vs KCl-saturated calomel electrode in 0.1 M phosphate buffer (pH 7.0) containing 0.100 M ascorbic acid was linear with the common logarithm of LIN concentration from 10.0 pM to 500 nM, with a limit of detection of 2.8 pM (S/N = 3). Satisfactory recovery results were obtained in the analysis of cow milk samples.

Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

Surface-immobilized cross-linked cationic polyelectrolyte enables CO2 reduction with metal cation-free acidic electrolyte.

Electrochemical CO2 reduction in acidic electrolytes is a promising strategy to achieve high utilization efficiency of CO2. Although alkali cations in acidic electrolytes play a vital role in suppressing hydrogen evolution and promoting CO2 reduction, they also cause precipitation of bicarbonate on the gas diffusion electrode (GDE), flooding of electrolyte through the GDE, and drift of the electrolyte pH. In this work, we realize the electroreduction of CO2 in a metal cation-free acidic electrolyte by covering the catalyst with cross-linked poly-diallyldimethylammonium chloride. This polyelectrolyte provides a high density of cationic sites immobilized on the surface of the catalyst, which suppresses the mass transport of H+ and modulates the interfacial field strength. By adopting this strategy, the Faradaic efficiency (FE) of CO reaches 95 ± 3% with the Ag catalyst and the FE of formic acid reaches 76 ± 3% with the In catalyst in a 1.0 pH electrolyte in a flow cell. More importantly, with the metal cation-free acidic electrolyte the amount of electrolyte flooding through the GDE is decreased to 2.5 ± 0.6% of that with alkali cation-containing acidic electrolyte, and the FE of CO maintains above 80% over 36 h of operation at -200 mA·cm-2.

Exosome-derived long noncoding RNAs: Mediators of host-Plasmodium parasite communication.

Overcoming challenges associated with malaria eradication proves to be a formidable task due to the complicated life cycle exhibited by the malaria parasite and the lack of safe and enduring vaccines against malaria. Investigating the interplay between Plasmodium parasites and their mammalian hosts is crucial for the development of novel vaccines. Long noncoding RNAs (lncRNAs) derived from Plasmodium parasites or host cells have emerged as potential signaling molecules involved in the trafficking of proteins, RNA (mRNAs, miRNAs, and ncRNAs), and DNA. These lncRNAs facilitate the interaction between hosts and parasites, impacting normal physiology or pathology in malaria-infected individuals. Moreover, they possess the capacity to regulate immune responses and associated signaling pathways, thus potentially influencing chromatin organization, epigenetic modifications, mRNA processing, splicing, and translation. However, the functional role of exosomal lncRNAs in malaria remains poorly understood. This review offers a comprehensive analysis of lncRNA and exosomal lncRNA profiles during malaria infection. It presents an overview of recent progress in elucidating the involvement of exosomal lncRNAs in host-parasite interactions. Additionally, potential exosomal lncRNAs linked to the domains of innate and adaptive immunity in the context of malaria are proposed. These findings may contribute to the discovery of new diagnostic and therapeutic strategies for malaria. Furthermore, the need for additional research was highlighted that aimed to elucidate the mechanisms underlying lncRNA transportation into host cells and their targeting of specific genes to regulate the host's immune response. This knowledge gap presents an opportunity for future investigations, offering innovative approaches to enhance malarial control. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease.

Rates of Intervention and Cancer Detection on Initial versus Subsequent Whole-body MRI Screening in Li-Fraumeni Syndrome.

Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown. Clinical data for pediatric and adult patients with LFS (n = 182) were reviewed, including instances of WB-MRI screening and interventions based on screening results. For each WB-MRI screening, interventions including biopsy and secondary imaging, as well as rate of cancer diagnosis, were analyzed comparing initial versus subsequent WB-MRI. Of the total cohort (n = 182), we identified 68 adult patients and 50 pediatric patients who had undergone at least two WB-MRI screenings, with a mean of 3.8 ± 1.9 (adults) and 4.0 ± 2.1 (pediatric) screenings. Findings on initial screening led to an imaging or invasive intervention in 38% of adults and 20% of children. On follow up, overall intervention rates were lower for adults (19%, P = 0.0026) and stable for children (19%, P = NS). Thirteen cancers were detected overall (7% of adult and 14% of pediatric scans), on both initial (pediatric: 4%, adult: 3%) and subsequent (pediatric: 10%, adult: 6%) screenings. Rates of intervention after WB-MRI screening decreased significantly in adults between first and subsequent exams and remained stable in pediatric patients. Cancer detection rates were similar on screening (3%-4% initial, 6%-10% subsequent) for both children and adults. These findings provide important data for counseling patients with LFS about screening outcomes. PREVENTION RELEVANCE: The cancer detection rate, burden of recommended interventions, and rate of false-positive findings found on subsequent WB-MRI screenings in patients with LFS are not well understood. Our findings suggest that annual WB-MRI screening has clinical utility and likely does not result in an unnecessary invasive intervention burden for patients.

Enhancing rice production sustainability and resilience via reactivating small water bodies for irrigation and drainage.

Rice farming threatens freshwater resources, while also being increasingly vulnerable to drought due to climate change. Rice farming needs to become more sustainable and resilient to climate change by improving irrigation drainage systems. Small water bodies, used to store drainage water and supply irrigation in traditional rice farming systems have gradually been abandoned in recent decades. This has resulted in a higher water footprint (WF) associated with rice farming due to increased freshwater usage and wastewater release, also leaving rice production more vulnerable to extreme weather events. Here, we propose how protecting and reactivating small water bodies for rice irrigation and drainage can decrease rice production WF in China by 30%, save 9% of China's freshwater consumption, increase irrigation self-sufficiency from 3% to 31%, and alleviate yield loss in dry years by 2-3%. These findings show that redesigning rice irrigation drainage systems can help meet water scarcity challenges posed by climate change.