Explainable Deep Learning-Assisted Self-Calibrating Colorimetric Patches for In Situ Sweat Analysis.

Sweat has emerged as a compelling analyte for noninvasive biosensing technology because it contains a wealth of important biomarkers in hormones, organic biomacromolecules, and various ionic mixtures. These components offer valuable insights and can reflect an individual's physiological conditions. Here, we introduced an explainable deep learning (DL)-assisted wearable self-calibrating colorimetric biosensing analysis platform to efficiently and precisely detect the biomarker's concentration in sweat. Specifically, we have integrated the advantages of the colorimetric sensing method, adsorbing-swelling hydrogel, and explainable DL algorithms to develop an enzyme/indicator-immobilized colorimetric patch, which has reliable colorimetric sensing ability and excellent adsorbing-swelling function. A total of 5625 colorimetric images were collected as the analysis data set and assessed two DL algorithms and seven machine learning (ML) algorithms. Zn2+, glucose, and Ca2+ in human sweats could be facilely classified and quantified with 100% accuracy via the convolutional neural network (CNN) model, and the testing results of actual sweats via the DL-assisted colorimetric approach are 91.7-97.2% matching with the classical UV-vis spectrum. Class activation mapping (CAM) was utilized to visualize the inner working mechanism of CNN operation, which contributes to verify and explicate the design rationality of the noninvasive biosensing technology. An "end-to-end" model was established to ascertain the black box of the DL algorithm, promoted software design or principium optimization, and contributed facile indicators for health monitoring, disease prevention, and clinical diagnosis.

TTK inhibition activates STING signal and promotes anti-PD1 immunotherapy in breast cancer.

Despite progress in the application of checkpoint immunotherapy against various tumors, attempts to utilize immune checkpoint blockade (ICB) agents in triple negative breast cancer (TNBC) have yielded limited clinical benefits. The low overall response rate of checkpoint immunotherapy in TNBC may be attributed to the immunosuppressive tumor microenvironment (TME). In this study, we investigated the role of mitogen-associated kinase TTK in reprogramming immune microenvironment in TNBC. Notably, TTK inhibition by BAY-1217389 induced DNA damage and the formation of micronuclei containing dsDNA in the cytosol, resulting in elicition of STING signal pathway and promoted antitumor immunity via the infiltration and activation of CD8+ T cells. Moreover, TTK inhibition also upregulated the expression of PD-L1, demonstrating a synergistic effect with anti-PD1 therapy in 4T1 tumor-bearing mice. Taken together, TTK inhibition facilitated anti-tumor immunity mediated by T cells and enhanced sensitivity to PD-1 blockade, providing a rationale for the combining TTK inhibitors with immune checkpoint blockade in clinical trials.

Metal-Free Electron Donor-Acceptor Pair Enabled Long-Term Stability of Li-CO2 Battery.

The challenges of Lithium-carbon dioxide (Li-CO2) batteries for ensuring long-term cycling stability arise from the thermodynamically stable and electrically insulating discharge products (e.g., Li2CO3), which primarily rely on their interaction with the active materials. To achieve the optimized intermediates, the bifunctional electron donor-acceptor (D-A) pairs are proposed in cathode design to adjust such interactions in the case of B-O pairs. The inclusion of BC2O sites allows for the optimized redistribution of electrons via p-π conjugation. The as-obtained DO-AB pairs endow the enhanced interactions with Li+, CO2, and various intermediates, accompanied by the adjustable growth mode of Li2CO3. The shift from solvation-mediated mode into surface absorption mode in turn manipulates the morphology and decomposition kinetics of Li2CO3. Therefore, the corresponding Li-CO2 battery got twofold improved in both the capacity and reversibility. The cycling prolongs exceed 1300 h and well operates at a wide temperature range (20-50 °C) and different folding angles (0-180°). Such a strategy of introducing electron donor-acceptor pairs provides a distinct direction to optimize the lifetime of Li-CO2 battery from local structure regulation at the atomic scale, further inspiring in-depth understandings for developing electrochemical energy storage and carbon capture technologies.

Mast cell stabilizer, an anti-allergic drug, reduces ventricular arrhythmia risk via modulation of neuroimmune interaction.

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.

Inverse Association between the Global Diet Quality Score and New-Onset Hypertension in Adults: A Nationwide Cohort Study.

BACKGROUND: The Global Diet Quality Score (GDQS) is a simple and practical dietary metric associated with a number of chronic diseases. The GDQS included various foods related to blood pressure, especially diverse plant-based foods that have shown to lower blood pressure. However, studies on the role of the GDQS in reducing the risk of new-onset hypertension and whether its performance differs from that of other dietary metrics are lacking. OBJECTIVE: We aimed to examine the association between the GDQS and new-onset hypertension and to compare its performance with that of other dietary patterns, including the Plant-based Diet Index (PDI), alternate Mediterranean diet (aMED) score, Alternative Healthy Eating Index-2010, and Dietary Approaches to Stop Hypertension (DASH) score in Chinese adults. METHODS: We included a total of 12,002 participants (5644 males and 6358 females) aged >18 y from the China Health and Nutrition Survey (1997-2015). Dietary intake was estimated using average food intakes from 3 consecutive 24-h dietary recalls. Multivariable relative risks (RRs) were computed for hypertension using modified Poisson regression models. RESULTS: With ≤18 y of follow-up (mean 8.7± 5.4 y), we ascertained 4232 incident cases of hypertension. Compared with participants with a low GDQS score (<15), the multivariable-adjusted RR of hypertension was 0.72 [95% confidence interval (CI): 0.62, 0.83] among participants with a high score (≥23). A 25% increment in the GDQS was associated with a 30% (RR, 0.70; 95% CI: 0.64, 0.76) lower risk of new-onset hypertension, which was comparable with the RRs of new-onset hypertension associated with every 25% increment in the PDI (RR, 0.84; 95% CI: 0.76, 0.93), DASH score (RR, 0.84; 95% CI: 0.78, 0.91), and aMED score (RR, 0.89; 95% CI: 0.84, 0.93). CONCLUSION: A higher GDQS was associated with a lower risk of new-onset hypertension, with comparable associations of new-onset hypertension with PDI, DASH, and aMED scores in Chinese adults.

Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

Ultrafast dynamics of fluorene initiated by highly intense laser fields.

We present an investigation of the ultrafast dynamics of the polycyclic aromatic hydrocarbon fluorene initiated by an intense femtosecond near-infrared laser pulse (810 nm) and probed by a weak visible pulse (405 nm). Using a multichannel detection scheme (mass spectra, electron and ion velocity-map imaging), we provide a full disentanglement of the complex dynamics of the vibronically excited parent molecule, its excited ionic states, and fragments. We observed various channels resulting from the strong-field ionization regime. In particular, we observed the formation of the unstable tetracation of fluorene, above-threshold ionization features in the photoelectron spectra, and evidence of ubiquitous secondary fragmentation. We produced a global fit of all observed time-dependent photoelectron and photoion channels. This global fit includes four parent ions extracted from the mass spectra, 15 kinetic-energy-resolved ionic fragments extracted from ion velocity map imaging, and five photoelectron channels obtained from electron velocity map imaging. The fit allowed for the extraction of 60 lifetimes of various metastable photoinduced intermediates.

The association between the triglyceride-glucose index and in-stent restenosis in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Insulin resistance (IR) can lead to cellular metabolic disorders, activation of oxidative stress, and endothelial dysfunction, contributing to in-stent restenosis (ISR). The triglyceride-glucose index (TyG index), a new indicator reflecting IR, is extensively researched in the cardiovascular field. This study, through a meta-analysis, aimed to utilize a larger combined sample size and thereby enhance the overall test efficacy to explore the TyG index-ISR relationship. METHODS: A thorough search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane Library databases to find original papers and their references published between 1990 and January 2024. This search included both prospective and retrospective studies detailing the correlation between the TyG index and ISR in individuals with coronary heart disease (CHD). OUTCOMES: The five included articles comprised 3,912 participants, and the odds ratio (OR) extracted from each study was combined using the Inverse Variance method. Results showed that, in the context of CHD patients, each incremental unit in the TyG index, when treated as a continuous variable, corresponded to a 42% elevation in ISR risk (95% CI 1.26-1.59, I²=13%, p < 0.005). When analyzing the TyG index categorically, the results revealed a higher ISR risk in the highest TyG index group compared to the lowest group (OR: 1.69, 95% CI 1.32-2.17, I²=0). Additionally, in patients with chronic coronary syndrome (CCS), each unit increase in the TyG index, the risk of ISR in patients increased by 37% (95% CI 1.19-1.57, I²=0%, p < 0.005). This correlation was also observable in acute coronary syndrome (ACS) patients (OR:1.48, 95% CI 1.19-1.85, I²=0, p < 0.005). CONCLUSIONS: The TyG index, an economical and precise surrogate for IR, is significantly linked with ISR. Furthermore, this correlation is unaffected by the type of coronary heart disease.

B(a)P induces ovarian granulosa cell apoptosis via TRAF2-NFκB-Caspase1 axis during early pregnancy.

Benzo(a)pyrene [B(a)P] is an environmental endocrine disruptor with reproductive toxicity. The corpus luteum (CL) of the ovary plays an important role in embryo implantation and pregnancy maintenance. Our previous studies have shown that B(a)P exposure affects embryo implantation and endometrial decidualization in mouse, but its effects and mechanisms on CL function remain unclear. In this study, we explore the mechanism of ovarian toxicity of B(a)P using a pregnant mouse model and an in vitro model of human ovarian granulosa cells (GCs) KGN. Pregnant mice were gavaged with corn oil or 0.2 mg/kg.bw B(a)P from pregnant day 1 (D1) to D7, while KGN cells were treated with DMSO, 1.0IU/mL hCG, or 1.0IU/mL hCG plus benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), a B(a)P metabolite. Our findings revealed that B(a)P exposure damaged embryo implantation and reduced estrogen and progesterone levels in early pregnant mice. Additionally, in vitro, BPDE impaired luteinization in KGN cells. We observed that B(a)P/BPDE promoted oxidative stress (OS) and inflammation, leading to apoptosis rather than pyroptosis in ovaries and luteinized KGN cells. This apoptotic response was mediated by the activation of inflammatory Caspase1 through the cleavage of BID. Furthermore, B(a)P/BPDE inhibited TRAF2 expression and suppressed NFκB signaling pathway activation. The administration of VX-765 to inhibit the Caspase1 activation, over-expression of TRAF2 using TRAF2-pcDNA3.1 (+) plasmid, and BetA-induced activation of NFκB signaling pathway successfully alleviated BPDE-induced apoptosis and cellular dysfunction in luteinized KGN cells. These findings were further confirmed in the KGN cell treated with H2O2 and NAC. In conclusion, this study elucidated that B(a)P/BPDE induces apoptosis rather than pyroptosis in GCs via TRAF2-NFκB-Caspase1 during early pregnancy, and highlighting OS as the primary contributor to B(a)P/BPDE-induced ovarian toxicity. Our results unveil a novel role of TRAF2-NFκB-Caspase1 in B(a)P-induced apoptosis and broaden the understanding of mechanisms underlying unexplained luteal phase deficiency.

Cinnamaldehyde Regulates the Migration and Apoptosis of Gastric Cancer Cells by Inhibiting the Jak2/Stat3 Pathway.

OBJECTIVE: Gastric cancer is a malignant tumor with high morbidity and mortality all around the world. Because of its poor prognosis and low survival rate, the treatment of gastric cancer has received extensive attention. Cinnamaldehyde (CA) is the main single active component of the Chinese herbal medicine cinnamon, which has a variety of pharmacological effects. The inhibitory effect of CA on the growth of some tumor cells has been proven, but its therapeutic effect on gastric cancer has rarely been reported. METHODS: Through network pharmacology, bioinformatics methods, and molecular docking technology, we predicted the interaction targets of CA and gastric cancer. Moreover, we found that apoptosis is an important mode of action of CA on gastric cancer cells. Subsequently, we validated it in gastric cancer cell lines cultured in vitro. RESULTS: The results showed that in the presence of CA, the Jak2/Stat3 pathway was inhibited, the ratio of Bcl-2/Bax decreased, and the apoptosis of gastric cancer cells was promoted in a concentration-dependent. CONCLUSION: In conclusion, CA can promote the apoptosis of gastric cancer cells by inhibiting the activity of the Jak2/Stat3 pathway, which may achieve the effect of treating gastric cancer.

Efficacy of hepatectomy for hepatolithiasis using 3D visualization combined with ICG fluorescence imaging: A retrospective cohort study.

BACKGROUND: Hepatolithiasis is a complex condition that poses challenges and difficulties in surgical treatment. Three-dimensional visualization technology combined with fluorescence imaging (3DVT-FI) enables accurate preoperative assessment and real-time intraoperative navigation. However, the perioperative outcomes of 3DVT-FI in hepatolithiasis have not been reported. We aim to evaluate the efficacy of 3DVT-FI in the treatment of hepatolithiasis. METHODS: A retrospective analysis was performed on 128 patients who underwent hepatectomy for hepatolithiasis at the Department of Hepatobiliary Surgery, Zhujiang Hospital, between January 2017 and December 2022. Among them, 50 patients underwent hepatectomy using 3DVT-FI (3DVT-FI group), while 78 patients underwent conventional hepatectomy without 3DVT-FI (CH group). The operative data, postoperative liver function indices, complication rates and stone residue were compared between the two groups. RESULTS: There were no significant differences in preoperative baseline data between the two groups (p > 0.05). Compared with the CH group, the 3DVT-FI group exhibited lower intraoperative blood loss (140.00 ± 112.12 vs. 225.99 ± 186.50 mL, p = 0.001), and a lower intraoperative transfusion rate (8.0% vs. 23.1%, p = 0.027). The overall incidence of postoperative complications did not differ significantly (22.0% vs. 35.9%, p = 0.096). The 3DVT-FI group was associated with a lower immediate residual stone rate (16.0% vs. 34.6%, p = 0.021). There were no perioperative deaths in the 3DVT-FI group, while one perioperative death occurred in the CH group. CONCLUSIONS: The 3DVT-FI may offer significant benefits in terms of surgical safety, reduced intraoperative bleeding and decreased stone residue during hepatectomy for hepatolithiasis.

Inter-leg systolic blood pressure difference has been associated with all-cause and cardiovascular mortality: analysis of NHANES 1999-2004.

BACKGROUND: Inter-leg systolic blood pressure difference (ILSBPD) has emerged as a novel cardiovascular risk factor. This study aims to investigate the predictive value of ILSBPD on all-cause and cardiovascular mortality in general population. METHODS: We combined three cycles (1999-2004) of the National Health and Nutrition Examination Survey (NHANES) data. Levels of ILSBPD were calculated and divided into four groups based on three cut-off values of 5, 10 and 15mmHg. Time-to-event curves were estimated with the use of the Kaplan-Meier method, and two multivariable Cox proportional hazards regression models were conducted to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cardiovascular mortality associated with ILSBPD. RESULTS: A total of 6 842 subjects were included, with the mean (SD) age of 59.5 (12.8) years. By December 31, 2019, 2 544 and 648 participants were identified all-cause and cardiovascular mortality respectively during a median follow-up of 16.6 years. Time-to-event analyses suggested that higher ILSBPD was associated with increased all-cause and cardiovascular mortality (logrank, p < 0.001). Every 5mmHg increment of ILSBPD brings about 5% and 7% increased risk of all-cause and cardiovascular mortality, and individuals with an ILSBPD ≥ 15mmHg were significantly associated with higher incidence of all-cause mortality (HR 1.43, 95%CI 1.18-1.52, p < 0.001) and cardiovascular mortality (HR 1.73, 95%CI 1.36-2.20, p < 0.001) when multiple confounding factors were adjusted. Subgroup and sensitivity analysis confirmed the relationship. CONCLUSIONS: Our findings suggest that the increment of ILSBPD was significantly associated with higher risk of all-cause and cardiovascular mortality in general population.

Unveiling the Role of Protein Kinase C θ in Porcine Epidemic Diarrhea Virus Replication: Insights from Genome-Wide CRISPR/Cas9 Library Screening.

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection.

Chemical Compositions of Scutellaria baicalensis Georgi. (Huangqin) Extracts and Their Effects on ACE2 Binding of SARS-CoV-2 Spike Protein, ACE2 Activity, and Free Radicals.

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals. A total of 76 compounds were tentatively identified from the extracts. The water extract showed a greater inhibition on the interaction between SARS-CoV-2 spike protein and ACE2, but less inhibition on ACE2 activity than that of the ethanol extract on a per botanical weight concentration basis. The total phenolic content was 65.27 mg gallic acid equivalent (GAE)/g dry botanical and the scavenging capacities against HO●, DPPH●, and ABTS●+ were 1369.39, 334.37, and 533.66 µmol trolox equivalent (TE)/g dry botanical for the water extract, respectively. These values were greater than those of the ethanol extract, with a TPC of 20.34 mg GAE/g, and 217.17, 10.93, and 50.21 µmol TE/g against HO●, DPPH●, and ABTS●+, respectively. The results suggested the potential use of huangqin as a functional food ingredient in preventing COVID-19.

Effects of additive on formation and electron transfer capacity of humic substances derived from silkworm-excrement compost during composting.

Amending biochar or MnO2 is a common strategy to regulate humification during manure composting. However, how these additives affect the formation, spectrum characteristics (UV-vis, FTIR, EEM) of humic substances (HSs) in silkworm-excrement (SE) compost and their electron transfer capacities (ETC) remains unclear. Thus, the SE composting pilot separately added with 10% corncob biochar (CB) (w/w) and 0.5% MnO2 (w/w) was run to investigate the effects. The results revealed that adding 10% CB slightly affected the HA/FA (humic acids/fulvic acids) ratios, UV-vis and FTIR spectra of the final SE-compost HSs and EEM components in the FA, but remarkably improved fulvic-like (C1)/quinone-like (C3) substances and reduced humic-like (C2)/protein-like substances (C4) in the HA. Meanwhile, 0.5% MnO2 had a noticeable positive effect on the aromatization of SE-compost FA and HA but only weak impact on SUVAs and EEM components in these HSs except C4 in the FA. Moreover, 10% CB obviously reduced EAC/EDC of FA and HA in the final SE compost by 31.1%/22.0% and 19.7%/24.0%, while MnO2 improved EDC of these HSs by 6.5%/9.1% (FA/HA). These results showed MnO2 can be used as a useful amendment to enhance the promotion effect of SE-compost HA in the soil remediation other than CB. Further investigation is suggested to focus on the effects of adding MnO2 on SE-compost HSs enhancing soil remediation and its effect on ETC derived from other manure compost.

eDNA reveals spatial homogenization of fish diversity in a mountain river affected by a reservoir cascade.

One of the main reasons for the decline in global freshwater biodiversity can be attributed to alterations in hydrological conditions resulting from dam construction. However, the majority of current research has focused on single or limited numbers of dams. Here, we carried out a seasonal fish survey, using environmental DNA (eDNA) method, on the Wujiang River mainstream (Tributaries of the Yangtze River, China) to investigate the impact of large-scale cascade hydropower development on changes in fish diversity patterns. eDNA survey revealed that native fish species have decreased in contrast to alien fish. There was also a shift in fish community structure, with declines of the dominant rheophilic fish species, an increase of the small-size fish species, and homogenization of species composition across reservoirs. Additionally, environmental factors, such as temperature, dissolved oxygen and reservoir age, had a significant effect on fish community diversity. This study provides basic information for the evaluation of the impact of cascade developments on fish diversity patterns.

Role of ventrolateral part of ventromedial hypothalamus in post-myocardial infarction cardiac dysfunction induced by sympathetic nervous system.

Psychological stress has been recognized as a contributing factor to worsened prognosis in patients with cardiac failure following myocardial infarction (MI). Although the ventrolateral part of the ventromedial hypothalamus (VMHVL) has been implicated in emotional distress, its involvement in post-MI cardiac dysfunction remains largely unexplored. This study was designed to investigate the effect of the VMHVL activation in the MI rat model and its underlying mechanisms. Our findings demonstrate that activation of VMHVL neurons enhances the activity of the cardiac sympathetic nervous system through the paraventricular nucleus (PVN) and superior cervical ganglion (SCG). This activation leads to an elevation in catecholamine levels, which subsequently modulates myosin function and triggers the release of anti-inflammatory factors, to exacerbate the post-MI cardiac prognosis. The denervation of the superior cervical ganglion (SGN) effectively blocked the cardiac sympathetic effects induced by the VMHVL activation, and ameliorated the cardia fibrosis and dysfunction. Therefore, our study identified the role of the "VMHVL-PVN-SCG" sympathetic pathway in the post-MI heart, and proposed SGN as a promising strategy in mitigating cardiac prognosis in stressful rats.

A new circular RNA-encoded protein BIRC6-236aa inhibits transmissible gastroenteritis virus (TGEV)-induced mitochondrial dysfunction.

Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially expressed circular RNAs (cRNA)from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function. Furthermore, mitochondrial permeability transition, a key step in the process of mitochondrial dysfunction, is known to be caused by abnormal opening of mitochondrial permeability transition pores (mPTPs) regulated by the voltage-dependent anion-selective channel protein 1 (VDAC)-Cyclophilin D (CypD) complex. Therefore, in the present study, we investigated the effects of circBIRC6-2 on mitochondrial dysfunction and opening of mPTPs. We found that TGEV infection reduced circBIRC6-2 levels, which in turn reduced mitochondrial calcium (Ca2+) levels, the decrease of mitochondrial membrane potential, and opening of mPTPs. In addition, we also identified ORFs and internal ribosomal entrance sites within the circBIRC6-2 RNA. We demonstrate circBIRC6-2 encodes a novel protein, BIRC6-236aa, which we show inhibits TGEV-induced opening of mPTPs during TGEV infection. Mechanistically, we identified an interaction between BIRC6-236aa and VDAC1, suggesting that BIRC6-236aa destabilizes the VDAC1-CypD complex. Taken together, the results suggest that the novel protein BIRC6-236aa encoded by cRNA circBIRC6-2 inhibits mPTP opening and subsequent mitochondrial dysfunction by interacting with VDAC1.

The origin, progress, and application of cell-based cardiac regeneration therapy.

Cardiovascular disease (CVD) has become a severe threat to human health, with morbidity and mortality increasing yearly and gradually becoming younger. When the disease progresses to the middle and late stages, the loss of a large number of cardiomyocytes is irreparable to the body itself, and clinical drug therapy and mechanical support therapy cannot reverse the development of the disease. To explore the source of regenerated myocardium in model animals with the ability of heart regeneration through lineage tracing and other methods, and develop a new alternative therapy for CVDs, namely cell therapy. It directly compensates for cardiomyocyte proliferation through adult stem cell differentiation or cell reprogramming, which indirectly promotes cardiomyocyte proliferation through non-cardiomyocyte paracrine, to play a role in heart repair and regeneration. This review comprehensively summarizes the origin of newly generated cardiomyocytes, the research progress of cardiac regeneration based on cell therapy, the opportunity and development of cardiac regeneration in the context of bioengineering, and the clinical application of cell therapy in ischemic diseases.

Nano-Structural Superwetting Surfaces for Highly Reliable On-Site Detection of Bisphenol A.

In the domain of big data geographic screening for environmental pollutants, the expeditious dissemination of testing results to environmental investigation professionals is pivotal in facilitating comprehensive analysis and the implementation of more efficacious strategies for managing environmental issues. However, this endeavor can prove to be particularly arduous when conducting examinations in remote, resource-scarce rural areas and field environments, where deficient infrastructure often emerges as the principal impediment to unimpeded environmental monitoring. Therefore, the development of a reliable and portable monitoring strategy with the ability to analyze large amounts of data is highly required. Here, a deep-learning (DL)-assisted portable sensing strategy was developed based on thermal and pH dual-responsive nano-structural superwetting surfaces, for highly reliable, quick, and field monitoring of environmental pollutants. In our experiment, bisphenol A (BPA) was selected as the representative pollute. The achieved limit of detection, attaining a remarkably low value of 1.05 µM, unequivocally adhered to stringent international testing standards for evaluating the migration of BPA in thermal paper. Based on a DL image classification algorithm, highly precise predictions regarding the migration of BPA concentration were achieved, with an accuracy rate exceeding 99%. Furthermore, it successfully facilitated automated and exceedingly reliable monitoring of the migration of BPA from thermal paper within the principal provinces of thermal paper production in China. This strategy engenders the potential to establish correlations between environmental pollutant concentrations in specific regions and the prevalence of certain human ailments.