Compact RNA editors with natural miniature Cas13j nucleases.

Clustered regularly interspaced short palindromic repeats-Cas13 effectors are used for RNA editing but the adeno-associated virus (AAV) packaging limitations because of their big sizes hinder their therapeutic application. Here we report the identification of the Cas13j family, with LepCas13j (529 aa) and ChiCas13j (424 aa) being the smallest and most highly efficient variants for RNA interference. The miniaturized Cas13j proteins enable the development of compact RNA base editors. Chi-RESCUE-S, by fusing dChiCas13j with hADAR2dd, demonstrates high efficiency and specificity in A-to-G and C-to-U conversions. Importantly, this system is compatible with single-AAV packaging without the need for protein sequence truncation. It successfully corrected pathogenic mutations, such as APOC3D65N and SCN9AR896Q, to the wild-type forms. In addition, we developed an optimized system, Chi-RESCUE-S-mini3, which pioneered efficient in vivo C-to-U RNA editing of PCSK9 in mice through single-AAV delivery, resulting in reduced total cholesterol levels. These results highlight the potential of Cas13j to treat human diseases.

Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.

The relationship between triglyceride-glucose index and prospective key clinical outcomes in patients hospitalised for coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is regarded as a dependable alternative for assessing insulin resistance (IR), given its simplicity, cost-effectiveness, and strong correlation with IR. The relationship between the TyG index and adverse outcomes in patients with coronary heart disease (CHD) is not well established. This study examines the association of the TyG index with long-term adverse outcomes in hospitalized CHD patients. METHODS: In this single-center prospective cohort study, 3321 patients hospitalized with CHD were included. Multivariate Cox regression models were employed to assess the associations between the TyG index and the incidence of all-cause mortality and major adverse cardiovascular events (MACEs). To examine potential nonlinear associations, restricted cubic splines and threshold analysis were utilized. RESULTS: During a follow-up period of 9.4 years, 759 patients (22.9%) succumbed to mortality, while 1291 (38.9%) experienced MACEs. Threshold analysis demonstrated a significant "U"-shaped nonlinear relationship with MACEs, with different hazard ratios observed below and above a TyG index of 8.62 (below: HR 0.71, 95% CI 0.50-0.99; above: HR 1.28, 95% CI 1.10-1.48). Notably, an increased risk of all-cause mortality was observed only when the TyG index exceeded 8.77 (HR 1.53, 95% CI 1.19-1.96). CONCLUSIONS: This study reveals a nonlinear association between the TyG index and both all-cause mortality and MACEs in hospitalized CHD patients with CHD. Assessing the TyG index, particularly focusing on individuals with extremely low or high TyG index values, may enhance risk stratification for adverse outcomes in this patient population.

Capacity enhancement through entropy loading with probabilistically shaped signals in a frequency comb-based transmission system.

We demonstrate a multichannel entropy loading mechanism in an optical frequency comb-based coherent communication system. In high-capacity wavelength division multiplexing communications, the individual laser sources can be replaced by an optical frequency comb, thus reducing the complexity and energy consumption of the transmitter. However, the power variation among different comb lines will lead to performance discrepancies. Spectral flattening filters can be adopted to suppress the variation at the expense of an additional system loss. Alternatively, by applying probabilistic shaping, we have implemented multichannel entropy loading to facilitate a continuous adaptation of the source entropy. The data rate can be dynamically allocated according to the performance of each channel. Through the loading scheme, the non-uniform performances across the channels are effectively mitigated, achieving a capacity enhancement of 34.91 Gbit/s.

Strategies to enhance the ability of nerve guidance conduits to promote directional nerve growth.

Severely damaged peripheral nerves will regenerate incompletely due to lack of directionality in their regeneration, leading to loss of nerve function. To address this problem, various nerve guidance conduits (NGCs) have been developed to provide guidance for nerve repair. However, their clinical application is still limited, mainly because its effect in promoting nerve repair is not as good as autologous nerve transplantation. Therefore, it is necessary to enhance the ability of NGCs to promote directional nerve growth. Strategies include preparing various directional structures on NGCs to provide contact guidance, and loading various substances on them to provide electrical stimulation or neurotrophic factor concentration gradient to provide directional physical or biological signals.

Magnesium polypeptide combined with microbially induced calcite precipitation for remediation of lead contamination in phosphate mining wasteland soil.

Soil Pb contamination is inevitable, as a result of phosphate mining. It is essential to explore more effective Pb remediation approaches in phosphate mining wasteland soil to ensure their viability for a gradual return of soil quality for cultivation. In this study, a Pb-resistant urease-producing bacterium, Serratia marcescens W1Z1, was screened for remediation using microbially induced carbonate precipitation (MICP). Magnesium polypeptide (MP) was prepared from soybean meal residue, and the combined remediation of Pb contamination with MP and MICP in phosphate mining wasteland soil was studied. Remediation of Pb using a combination of MP with MICP strain W1Z1 (WM treatment) was the most effective, with the least exchangeable Pb at 30.37% and the most carbonate-bound Pb at 40.82%, compared to the other treatments, with a pH increase of 8.38. According to the community analysis, MP moderated the damage to microbial abundance and diversity caused by MICP. Total nitrogen (TN) was positively correlated with Firmicutes, pH, and carbonate-bound Pb. Serratia inoculated with strain W1Z1 were positively correlated with bacteria belonging to the Firmicutes phylum and negatively correlated with bacteria belonging to Proteobacteria. The available phosphate (AP) in the phosphate mining wasteland soil could encapsulate the precipitated Pb by ion exchange with carbonate, making it more stable. Combined MP-MICP remediation of Pb contamination in phosphate mining wasteland soil was effective and improved the soil microenvironment.

The Impact of Valve Surgery on the Safety and Cardiac Function of Patients with Valvular Heart Disease Complicated by Pulmonary Arterial Hypertension.

Objective: This study evaluates the effects of valve surgery on safety and cardiac function in patients with valvular heart disease complicated by pulmonary arterial hypertension (PAH), focusing on postoperative outcomes influenced by age, heart function grade, and PAH severity. Methods: A retrospective analysis was conducted on 307 valve surgery patients from April 2017 to April 2022. The cohort had a mean age of 57.6 years, with 56.9% males, and was stratified by NYHA functional class II-IV. Outcomes assessed included mortality, complication rates, left ventricular ejection fraction (LVEF), and pulmonary artery systolic pressure (PASP), with statistical analysis performed using t-tests and chi-square tests for continuous and categorical data, respectively. Results: Postoperative outcomes varied significantly with age, NYHA class, and PASP grade. Patients aged ≤60 exhibited an average PASP reduction of 44.46% in the male group and 44.44% in the female group and an LVEF improvement of 5.28% in the male group and 5.80% in the female group. However, these patients showed a higher risk of postoperative complications, such as renal failure, arrhythmia, low cardiac output syndrome, respiratory insufficiency, (23.31%), and a higher mortality rate (13.53%)(P < .05). Higher NYHA classes correlated with increased postoperative risks of complications and mortality rates, and elevated PASP grades were associated with larger improvements in PASP and LVEF but also higher postoperative risks. Conclusion: Valve surgery in valvular heart disease with PAH is influenced by patient age, functional status, and PAH severity. Despite advances in surgical techniques, there remains a notable gap in understanding the nuanced interplay between these conditions and the variable outcomes of valve surgery. This study addresses this research gap, offering comprehensive insights into how age, heart function, and PAH severity influence postoperative outcomes. These findings are crucial for clinicians, providing a more informed basis for tailored treatment strategies, and ultimately enhancing patient care in this complex clinical scenario.Healthcare providers should consider the age-specific benefits and risks of valve surgery in patients with valvular heart disease and pulmonary arterial hypertension. Tailored decision-making, particularly for those aged ≤60, higher NYHA classes, or severe PAH, is essential for optimizing individual outcomes.

A Fusion-Growth Protocell Model Based on Vesicle Interactions with Pyrite Particles.

Protocell models play a pivotal role in the exploration of the origin of life. Vesicles are one type of protocell model that have attracted much attention. Simple single-chain amphiphiles (SACs) and organic small molecules (OSMs) possess primitive relevance and were most likely the building blocks of protocells on the early Earth. OSM@SAC vesicles have been considered to be plausible protocell models. Pyrite (FeS2), a mineral with primitive relevance, is ubiquitous in nature and plays a crucial role in the exploration of the origin of life in the mineral-water interface scenario. "How do protocell models based on OSM@SAC vesicles interact with a mineral-water interface scenario that simulates a primitive Earth environment" remains an unresolved question. Hence, we select primitive relevant sodium monododecyl phosphate (SDP), isopentenol (IPN) and pyrite (FeS2) mineral particles to build a protocell model. The model investigates the basic physical and chemical properties of FeS2 particles and reveals the effects of the size, content and duration of interaction of FeS2 particles on IPN@SDP vesicles. This deepens the understanding of protocell growth mechanisms in scenarios of mineral-water interfaces in primitive Earth environments and provides new information for the exploration of the origin of life.

Regulating Intermolecular Interactions and Film Formation Kinetics for Record Efficiency in Difluorobenzothiadizole-Based Organic Solar Cells.

The difluorobenzothiadizole (ffBT) unit is one of the most classic electron-accepting building blocks used to construct D-A copolymers for applications in organic solar cells (OSCs). Historically, ffBT-based polymers have achieved record power conversion efficiencies (PCEs) in fullerene-based OSCs owing to their strong temperature-dependent aggregation (TDA) characteristics. However, their excessive miscibility and rapid aggregation kinetics during film formation have hindered their performance with state-of-the-art non-fullerene acceptors (NFAs). Herein, we synthesized two ffBT-based copolymers, PffBT-2T and PffBT-4T, incorporating different π-bridges to modulate intermolecular interactions and aggregation tendencies. Experimental and theoretical studies revealed that PffBT-4T exhibits reduced electrostatic potential differences and miscibility with L8-BO compared to PffBT-2T. This facilitates improved phase separation in the active layer, leading to enhanced molecular packing and optimized morphology. Moreover, PffBT-4T demonstrated a prolonged nucleation and crystal growth process, leading to enhanced molecular packing and optimized morphology. Consequently, PffBT-4T-based devices achieved a remarkable PCE of 17.5 %, setting a new record for ffBT-based photovoltaic polymers. Our findings underscore the importance of conjugate backbone modulation in controlling aggregation behavior and film formation kinetics, providing valuable insights for the design of high-performance polymer donors in organic photovoltaics.

Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.

Ischemia/reperfusion injury of the kidney is associated with high morbidity and mortality, and treatment of this injury remains a challenge. G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and myocardial infarction, but its function in kidney ischemia/reperfusion injury remains undetermined. Among the GRK subtypes (GRK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the other four GRKs 24 hours after injury and was found to accumulate in the nuclei of injured mouse and human renal tubule cells. Gain- and loss-of-function experiments revealed that GRK4 overexpression exacerbated acute kidney ischemia/reperfusion injury, whereas kidney tubule-specific knockout of GRK4 decreased injury-induced kidney dysfunction. Necroptosis was the major type of tubule cell death mediated by GRK4, because GRK4 significantly increased receptor interacting kinase (RIPK)1 expression and phosphorylation, subsequently leading to RIPK3 and mixed lineage kinase domain-like protein (MLKL) phosphorylation after kidney ischemia/reperfusion injury, but was reversed by necrostatin-1 pretreatment (an RIPK1 inhibitor). Using co-immunoprecipitation, mass spectrometry, and siRNA screening studies, we identified signal transducer and activator of transcription (STAT)1 as a GRK4 binding protein, which co-localized with GRK4 in the nuclei of renal tubule cells. Additionally, GRK4 phosphorylated STAT1 at serine 727, whose inactive mutation effectively reversed GRK4-mediated RIPK1 activation and tubule cell death. Kidney-targeted GRK4 silencing with nanoparticle delivery considerably ameliorated kidney ischemia/reperfusion injury. Thus, our findings reveal that GRK4 triggers necroptosis and aggravates kidney ischemia/reperfusion injury, and its downregulation may provide a promising therapeutic strategy for kidney protection.

ß-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.

Optimizing the probability mass function of complex modulated signals through adaptive channel characterization.

We propose a probability mass function (PMF) optimization scheme for quadrature amplitude modulation (QAM) signals by considering the parametric characteristic of the training sequence. The training sequence for optimization is mapped in standard Maxwell-Boltzmann (M-B) distribution, and the considered characterizing parameters incorporate either the noise variance or the error matrix of the received symbols. The proposed PMF optimization is based on independent reallocation within each constellation ring, generating new distribution with almost the same entropy and transmitted power as the original distribution. This reallocation mechanism is model-free and iterative-free with very low computational complexity. By characterizing the channel in terms of constellation performance asymmetry, PMF reallocation can be effectively implemented to supplement the existing equalization algorithm. The effectiveness of this approach is experimentally verified in a 40-km transmission system with 24 Gbaud 64-QAM signals under three different scenarios. Through PMF reallocation, we achieve generalized mutual information (GMI) improvement of ∼0.06 and throughput improvement of ∼1.5 Gbit/s before forward error correction in comparison with the standard M-B distribution. The proposed mechanism provides a solution to obtain the optimal PMF in practical communication channels, which suffer from various types of noises and distortions.

Anthocyanin attenuates high salt-induced hypertension via inhibiting the hyperactivity of the sympathetic nervous system.

BACKGROUND: Anthocyanin plays a protective role in cardiovascular disease through antioxidant effect. Whether anthocyanin can reduce salt-induced hypertension and the related mechanisms remain unclear. METHODS: Chronic infusion of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL/h) or anthocyanin (10 mg/kg, 0.4 µL/h) into bilateral paraventricular nucleus (PVN) of Sprague-Dawley rats was performed. Then, the rats were fed a high salt diet (8% NaCl, HS) or normal salt diet (0.9%, NaCl, NS) for 4 weeks. RESULTS: High salt diet induced an increase in blood pressure and peripheral sympathetic nerve activity (increased LF/HF and decreased SDNN and RMSSD), which was accompanied by increased reactive oxygen species (ROS) production and angiotensin II type-1 receptor (AT1R) expression and function in the PVN. Moreover, the NOD-like receptor protein 3 (NLRP3) and related inflammatory proteins (caspase-1) expression, the pro-inflammatory cytokine levels including IL-1ß and TNF-α were higher in PVN of rats with a high salt diet. Bilateral PVN infusion of anthocyanin attenuated NLRP3-dependent inflammation (NLRP3, caspase-1, IL-1ß and TNF-α) and ROS production, reduced AT1R expression and function in PVN and lowered peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension. CONCLUSIONS: Excessive salt intake activates NLRP3-dependent inflammation and oxidative stress and increased AT1R expression and function in the PVN. Bilateral PVN infusion of anthocyanin lowers peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension by improvement of expression and function of AT1R in the PVN through inhibiting NLRP3 related inflammatory and oxidative stress.

Xanchryones I-N, Six Unusual Phloroglucinol-Amino Acid Hybrids from the Leaves of Xanthostemon chrysanthus.

Six new phloroglucinol derivatives, xanchryones I-N (1-6), were isolated from the leaves of Xanthostemon chrysanthus. Compounds 1-6 are unusual phloroglucinol-amino acid hybrids constructed through C2 -N and O-C1 ' bonds forming a peculiar oxazole ring. The structures and absolute configurations of compounds 1-6 were determined by MS, NMR, and single-crystal X-ray diffraction. Moreover, the anti-inflammatory and antibacterial activities of these compounds were evaluated.

Membrane-delimited signaling and cytosolic action of MG53 preserve hepatocyte integrity during drug-induced liver injury.

BACKGROUND & AIMS: Drug-induced liver injury (DILI) remains challenging to treat and is still a leading cause of acute liver failure. MG53 is a muscle-derived tissue-repair protein that circulates in the bloodstream and whose physiological role in protection against DILI has not been examined. METHODS: Recombinant MG53 protein (rhMG53) was administered exogenously, using mice with deletion of Mg53 or Ripk3. Live-cell imaging, histological, biochemical, and molecular studies were used to investigate the mechanisms that underlie the extracellular and intracellular action of rhMG53 in hepatoprotection. RESULTS: Systemic administration of rhMG53 protein, in mice, can prophylactically and therapeutically treat DILI induced through exposure to acetaminophen, tetracycline, concanavalin A, carbon tetrachloride, or thioacetamide. Circulating MG53 protects hepatocytes from injury through direct interaction with MLKL at the plasma membrane. Extracellular MG53 can enter hepatocytes and act as an E3-ligase to mitigate RIPK3-mediated MLKL phosphorylation and membrane translocation. CONCLUSIONS: Our data show that the membrane-delimited signaling and cytosolic dual action of MG53 effectively preserves hepatocyte integrity during DILI. rhMG53 may be a potential treatment option for patients with DILI. LAY SUMMARY: Interventions to treat drug-induced liver injury and halt its progression into liver failure are of great value to society. The present study reveals that muscle-liver cross talk, with MG53 as a messenger, serves an important role in liver cell protection. Thus, MG53 is a potential treatment option for patients with drug-induced liver injury.

NLRP3 inflammasome contributes to endothelial dysfunction in angiotensin II-induced hypertension in mice.

AIMS: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension. MATERIALS AND METHODS: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice, treated with Ang II. In vitro, we mainly tested the endothelial nitric oxide synthase (eNOS) phosphorylation expression of human umbilical vein endothelial cells (HUVECs). KEY FINDINGS: Here we showed that 14-day Ang II infusion into mice resulted in the elevation of blood pressure, NLRP3 expression, serum interleukin (IL)-1ß level, and the decline of endothelium-dependent relaxation function, p-eNOS-Ser1177 expression in aortas. Nlrp3 deficiency reduced Ang II-induced blood pressure elevation and endothelial dysfunction. In vitro, NLRP3 was involved in the effect of Ang II on reducing p-eNOS-Ser1177 expression. Moreover, the direct effect of IL-1ß on vascular endothelial injury could be observed in both vivo and vitro. SIGNIFICANCE: Our result demonstrates that the NLRP3 inflammasome is critically involved in the detrimental effects of Ang II on vascular endothelium in hypertension via the activation of IL-1ß, placing NLRP3 as a potential target for therapeutic interventions in conditions with endothelial dysfunction in hypertension.

Characterization of the core gut microbiota of Nile tilapia (Oreochromis niloticus): indication of a putative novel Cetobacterium species and analysis of its potential function on nutrition.

The genus Cetobacterium has been considered a dominant group of gut bacteria in many freshwater fish, and members of this genus contribute to anaerobic metabolism. Because of its significant place in the gut of freshwater fish, many studies on Cetobacterium were performed. Those studies mostly focused on the temporal and spatial changes of its abundance in fish intestine, which were affected by food or other environmental conditions. However, only a few studies isolated strains from genus Cetobacterium and reported their characteristics. In the present study, we performed 16S rRNA sequencing of the intestinal mucosa of Nile tilapia (Oreochromis niloticus) and found that Cetobacterium sp. existed widely in the foregut, midgut and hindgut mucosa, and a strain of Cetobacterium was successfully isolated from the gut of tilapia. We sequenced its whole genome and predicted it to be a novel candidate species of Cetobacterium sp. and named it NK01. The size of its genome was 3,095,946 bp, with a guanine + cytosine content of 28.8%. Among the identified genes, 2855 were predicted to be coding DNA sequences, 84 were tRNA and 34 were rRNA. We found that NK01 produced amino acids, including leucine, isoleucine, valine, glycine, alanine, phenylalanine and proline. Strain NK01 could use starch, sucrose, maltose, glucose, and mannose and synthesize and utilize glycogen. INV, GPI, malQ, malZ, sacA, scrK, glgC, glgA and glk, which were related to carbohydrate metabolism, were detected. yiaY and adhE, which oxidize ethanol to acetaldehyde and participate in a variety of metabolic pathways, were also present in the genome. No coding genes directly involved in acetate or butyrate production were detected. NK01 could also catabolize a variety of vitamins, and all genes involved in folate synthesis were detected, including folP, folC, folA and eutT, which converted vitamin B12s into vitamin B12 coenzyme. Here, we investigated the draft genome and in vitro function of Cetobacterium isolated from the intestinal tract of Nile tilapia. The results provided a preliminary understanding of the core microbiota of fish gut.

Hemin mitigates contrast-induced nephropathy by inhibiting ferroptosis via HO-1/Nrf2/GPX4 pathway.

Contrast-induced nephropathy (CIN) is a common complication with adverse outcome after iodinated-contrast injection, yet still lacking effective medication. Heme oxygenase-1 (HO-1) has been reported to play an important role against renal injuries. Hemin, a HO-1 inducer and anti-porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK-2). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high-fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK-2 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down-expression by small interfering RNA (siRNA) reversed the effect of hemin on HK-2 cells. Furthermore, hemin's induction of GPX4 involved HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2). Either HO-1 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over-expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin-1 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO-1/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti-ferroptosis is a potential therapeutic strategy for CIN.

Optical electrocardiogram monitor with a real-time analysis of an abnormal heart rhythm for home-based medical alerts.

Sudden cardiac death (SCD) caused by cardiovascular disease is the greatest hidden danger to human life, accounting for about 25% of the total deaths in the world. Due to the early concealment of SCD and the heavy medical burden of long-term examination, telemedicine combined with home monitoring has become a potential medical alert method. Among all the existing human cardiac and electrophysiology monitoring methods, optics-based sensors attract the widest attention due to the advantages of low delay, real-time monitoring, and high signal-to-noise ratio. In this paper, we propose an optical sensor with the capabilities of long-term monitoring and real-time analysis. Combining an R-peak recognition algorithm, Lorenz plots (LP), and statistical analysis, we carried out the consistency analysis and result visualization of ECG sequences over 1 h. The results of 10 subjects show that the R-peak recognition accuracy of the optical ECG monitor is higher than 97.99%. The optical system can display abnormal heart rhythm in real-time through LP, and the readability is good, which makes the system suitable for self-monitoring at home. In addition, this paper provides a detailed long-term monitoring assessment method to effectively guide the practical clinical transformation of other optical wearable devices.

Comparative transcriptomic analysis between 'Summer Black' and its bud sport 'Nantaihutezao' during developmental stages.

MAIN CONCLUSION: 4-coumarate-CoA ligase (VIT_02s0109g00250) and copper amine oxidase (VIT_17s0000g09100) played essential roles in contributing to the total soluble solid and total anthocyanin variations induced by bud sport in grape berries. Taste and color, which are important organoleptic qualities of grape berry, undergo rapid and substantial changes during development and ripening. In this study, we used two cultivars 'Summer Black' and its bud sport 'Nantaihutezao' to explore and identify differentially expressed genes associated with total soluble solid and anthocyanin during developmental stages using RNA-Seq. Overall, substantial differences in expression were observed across berry development between the two cultivars. 5388 genes were detected by weighted gene co-expression network analysis (WGCNA) associated with the total soluble solid (TSS) and anthocyanin contents variations. Several of these genes were significantly enriched in the phenylalanine metabolism pathway; two hub genes 4-coumarate-CoA ligase (VIT_02s0109g00250) and copper amine oxidase (VIT_17s0000g09100) played the most essential roles in relating to the total soluble solid and total anthocyanin variations induced by bud sport through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and co-expression network analysis. These findings provide insights into the molecular mechanism responsible for the bud sport phenotype.