An Artificial Intelligence-Driven Approach for Automatic Evaluation of Right-to-Left Shunt Grades in Saline-Contrasted Transthoracic Echocardiography.

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.

Comparative transcriptome analysis of Fusarium graminearum challenged with distinct fungicides and functional analysis of FgICL gene.

Fusarium graminearum is an economically important phytopathogenic fungus. Chemical control remains the dominant approach to managing this plant pathogen. In the present study, we performed a comparative transcriptome analysis to understand the effects of four commercially used fungicides on F. graminearum. The results revealed a significant number of differentially expressed genes related to carbohydrate, amino acid, and lipid metabolism, particularly in the carbendazim and phenamacril groups. Central carbon pathways, including the TCA and glyoxylate cycles, were found to play crucial roles across all treatments except tebuconazole. Weighted gene co-expression network analysis reinforced the pivotal role of central carbon pathways based on identified hub genes. Additionally, critical candidates associated with ATP-binding cassette transporters, heat shock proteins, and chitin synthases were identified. The crucial functions of the isocitrate lyase in F. graminearum were also validated. Overall, the study provided comprehensive insights into the mechanisms of how F. graminearum responds to fungicide stress.

Influence of Zr Microalloying on the Microstructure and Room-/High-Temperature Mechanical Properties of an Al-Cu-Mn-Fe Alloy.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al-Cu-Mn-Fe (ACMF) and Al-Cu-Mn-Fe-Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ' phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ' precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ', which was assumed beneficial for stabilizing the θ' precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ' precipitates on the tensile properties were discussed. This work may be referred to for designing Al-Cu alloys for application in high-temperature fields.

Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production.

Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgGs production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgGs production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgGs production exhibited TIP (duration <60 days) and PIP (duration >368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were co-immunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgGs production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.

Comparison of the outcomes of concurrent versus staged TAVR combined with PCI in patients with severe aortic stenosis and coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: The optimal timing for percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) remains uncertain. This research aims to evaluate the results of patients diagnosed with severe aortic valve stenosis and coronary artery disease who undergo either simultaneous or staged PCI therapy during TAVR procedures. METHODS: We retrieved all relevant studies from our self-constructed databases up to January 2, 2024, encompassing databases such as Embase, Medline, Cochrane Library, and PubMed. RESULTS: A total of nine studies were included, and the results showed that both surgical modalities had good safety profiles in the early and long-term stages. For early endpoint events, the risk of all-cause mortality and major bleeding within 30 years was similar in the staged TAVR + PCI and the contemporaneous TAVR + PCI (P > 0.05). Additionally, the risk of myocardial infarction, stroke, acute kidney injury and pacemaker implantation within 30 days or perioperatively is similar (P > 0.05). For long-term endpoint events, the risk of all-cause mortality, myocardial infarction and stroke was similar in the two groups at ≥2 years (P > 0.05). CONCLUSION: In patients undergoing TAVR who required coronary revascularization, no significant differences were observed in the early and long-term outcomes between those receiving concurrent TAVR and PCI versus staged surgery.

Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial.

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. RESULTS: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. CONCLUSIONS: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04401800).

Genome-Wide Association Studies on Chinese Wheat Cultivars Reveal a Novel Fusarium Crown Rot Resistance Quantitative Trait Locus on Chromosome 3BL.

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, has emerged as a new threat to wheat production and quality in North China. Genetic enhancement of wheat resistance to FCR remains the most effective approach for disease control. In this study, we phenotyped 435 Chinese wheat cultivars through FCR inoculation at the seedling stage in a greenhouse. Our findings revealed that only approximately 10.8% of the wheat germplasms displayed moderate or high resistance to FCR. A genome-wide association study (GWAS) using high-density 660K SNP led to the discovery of a novel quantitative trait locus on the long arm of chromosome 3B, designated as Qfcr.hebau-3BL. A total of 12 significantly associated SNPs were closely clustered within a 1.05 Mb physical interval. SNP-based molecular markers were developed to facilitate the practical application of Qfcr.hebau-3BL. Among the five candidate FCR resistance genes within the Qfcr.hebau-3BL, we focused on TraesCS3B02G307700, which encodes a protein kinase, due to its expression pattern. Functional validation revealed two transcripts, TaSTK1.1 and TaSTK1.2, with opposing roles in plant resistance to fungal disease. These findings provide insights into the genetic basis of FCR resistance in wheat and offer valuable resources for breeding resistant varieties.

Uncovering the photosystem I assembly pathway in land plants.

Photosystem I (PSI) is one of two large pigment-protein complexes responsible for converting solar energy into chemical energy in all oxygenic photosynthetic organisms. The PSI supercomplex consists of the PSI core complex and peripheral light-harvesting complex I (LHCI) in eukaryotic photosynthetic organisms. However, how the PSI complex assembles in land plants is unknown. Here we describe PHOTOSYSTEM I BIOGENESIS FACTOR 8 (PBF8), a thylakoid-anchored protein in Arabidopsis thaliana that is required for PSI assembly. PBF8 regulates two key consecutive steps in this process, the building of two assembly intermediates comprising eight or nine subunits, by interacting with PSI core subunits. We identified putative PBF8 orthologues in charophytic algae and land plants but not in Cyanobacteria or Chlorophyta. Our data reveal the major PSI assembly pathway in land plants. Our findings suggest that novel assembly mechanisms evolved during plant terrestrialization to regulate PSI assembly, perhaps as a means to cope with terrestrial environments.

Enhancement of broad-spectrum disease resistance in wheat through key genes involved in systemic acquired resistance.

Systemic acquired resistance (SAR) is an inducible disease resistance phenomenon in plant species, providing plants with broad-spectrum resistance to secondary pathogen infections beyond the initial infection site. In Arabidopsis, SAR can be triggered by direct pathogen infection or treatment with the phytohormone salicylic acid (SA), as well as its analogues 2,6-dichloroisonicotinic acid (INA) and benzothiadiazole (BTH). The SA receptor non-expressor of pathogenesis-related protein gene 1 (NPR1) protein serves as a key regulator in controlling SAR signaling transduction. Similarly, in common wheat (Triticum aestivum), pathogen infection or treatment with the SA analogue BTH can induce broad-spectrum resistance to powdery mildew, leaf rust, Fusarium head blight, and other diseases. However, unlike SAR in the model plant Arabidopsis or rice, SAR-like responses in wheat exhibit unique features and regulatory pathways. The acquired resistance (AR) induced by the model pathogen Pseudomonas syringae pv. tomato strain DC3000 is regulated by NPR1, but its effects are limited to the adjacent region of the same leaf and not systemic. On the other hand, the systemic immunity (SI) triggered by Xanthomonas translucens pv. cerealis (Xtc) or Pseudomonas syringae pv. japonica (Psj) is not controlled by NPR1 or SA, but rather closely associated with jasmonate (JA), abscisic acid (ABA), and several transcription factors. Furthermore, the BTH-induced resistance (BIR) partially depends on NPR1 activation, leading to a broader and stronger plant defense response. This paper provides a systematic review of the research progress on SAR in wheat, emphasizes the key regulatory role of NPR1 in wheat SAR, and summarizes the potential of pathogenesis-related protein (PR) genes in genetically modifying wheat to enhance broad-spectrum disease resistance. This review lays an important foundation for further analyzing the molecular mechanism of SAR and genetically improving broad-spectrum disease resistance in wheat.

Discovery of the 2,4-disubstituted quinazoline derivative as a novel neddylation inhibitor for tumor therapy.

Overactivation of neddylation has been found in a number of common human tumor-related diseases. In recent years, targeting the neddylation pathway has become an appealing anti-cancer strategy, and it is critical to find neddylation inhibitors with novel structures and higher efficacy. Here, we present the discovery of novel inhibitors of the NEDD8-activating enzyme (NAE) and their antitumor activity in vitro. All synthesized 1,4-disubstituted piperidine compounds were evaluated for antiproliferative activity against MGC-803, MCF-7, A549, and KYSE-30 cells. Among five representative compounds, III-26 bearing a quinazoline motif was identified as the lead one due to the fact that it significantly hindered the neddylation of Cullin1. Cellular mechanisms elucidated that III-26 inhibited the proliferation, migration, and invasion of UBC12-overexpressed MGC-803 cell lines, as well as induced apoptosis and arrested the cell cycle at G2/M phase. Importantly, III-26 reduced NAE activity, thus selectively preventing neddylation of Cullin3 and Cullin1 over other Cullin members. At a dose of 4 µM, III-26 virtually entirely blocked UBC12-NEDD8 conjugation in MGC-803 cells. Our molecular modeling and kinetic investigation suggested that this compound may function as a non-covalent inhibitor of NAE.

Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation. Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay. Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1ß and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1ß also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice. Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.

Small extracellular vesicles derived from acute myeloid leukemia cells promote leukemogenesis by transferring miR-221-3p.

Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.

Identification of novel benzothiazole derivatives as inhibitors of NEDDylation pathway to inhibit the progression of gastric cancer.

The overexpression of neddylation modification is frequently observed in human tumor cells. Targeting the neddylation pathway has been recognized as a promising anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is of great importance. In this study, we designed and synthesized a series of novel neddylation inhibitors bearing benzothiazole scaffolds by molecular hybridization strategy and all compounds were evaluated for antiproliferative activity against MGC-803, MCF-7, A549 and KYSE-30 cell lines. In vitro anti-tumor studies showed that the most promising compound X-10, effectively suppressed MGC-803 cells growth and migration, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, by directly interacting with NAE1, X-10 blocked NAE1 activity, specifically preventing neddylation of Cullin 3 and Cullin 1, and produced a dose-response decline in the level of UBC12-NEDD8 complex. Overall, our data indicate that X-10 inhibits the process of neddylation, making it a potentially agent for both cancer prevention and therapy purposes.

Characterization of "microbiome-metabolome-immunity" in depressed rats with divergent responses to Paroxetine.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are the first-line anti-depressants. Unfortunately, about 30 % depressed patients do not effectively respond to SSRIs. It is still unclear that the gastrointestinal characteristics of responders and non-responders, and the differences. METHODS: Herein, we characterized gut microbiome and metabolome of depressed rats with differential responses to Paroxetine (PX) by 16S rRNA sequencing and 1H NMR-based metabolomics, respectively. On top of this, we constructed both inter- and inner-layer networks, intuitively showing the correlations among behavioral indicators, immune factors, intestinal bacteria, and differential metabolites. RESULTS: Consequently, we found that depressed rats differently responded to PX, which could be divided into PX responsive (PX-R) and non-responsive (PX-N) groups. Firstly, the depressive behaviors of PX-R rats and PX-N rats significantly differed. Meanwhile, inflammatory balance was also characterized for depressed rats with different responses to PX. Overall, PX-R rats and PX-N rats exhibited differential gut microbiome and metabolome, including intestinal structures, intestinal functions, metabolic profiles, metabolites, and metabolic pathways. LIMITATIONS: Metabolites that identified by metabolomics based on 1H NMR are not comprehensive enough. CONCLUSIONS: Taken together, our study demonstrated that gut microbiome and metabolome, as well as related functions, are of significance in differential responses of depressed rats to PX, which might be novel insights in uncovering the mechanisms of differences in efficacies of antidepressants.

Pyroptosis-related signatures predict immune characteristics and prognosis in IPF.

The purpose of this work was to use integrated bioinformatics analysis to screen for pyroptosis-related genes (PRGs) and possible immunological phenotypes linked to the development and course of IPF. Transcriptome sequencing datasets GSE70866, GSE47460 and GSE150910 were obtained from GEO database. From the GSE70866 database, 34 PRGs with differential expression were found in IPF as compared to healthy controls. In addition, a diagnostic model containing 4 genes PRGs (CAMP, MKI67, TCEA3 and USP24) was constructed based on LASSO logistic regression. The diagnostic model showed good predictive ability to differentiate between IPF and healthy, with ROC-AUC ranging from 0.910 to 0.997 in GSE70866 and GSE150910 datasets. Moreover, based on a combined cohort of the Freiburg and the Siena cohorts from GSE70866 dataset, we identified ten PRGs that might predict prognosis for IPF. We constructed a prognostic model that included eight PRGs (CLEC5A, TREM2, MMP1, IRF2, SEZ6L2, ADORA3, NOS2, USP24) by LASSO Cox regression and validated it in the Leuven cohort. The risk model divided IPF patients from the combined cohort into high-risk and low-risk subgroups. There were significant differences between the two subgroups in terms of IPF survival and GAP stage. There is a close correlation between leukocyte migration, plasma membrane junction, and poor prognosis in a high-risk subgroup. Furthermore, a high-risk score was associated with more plasma cells, activated NK cells, monocytes, and activated mast cells. Additionally, we identified HDAC inhibitors in the cMAP database that might be therapeutic for IPF. To summarize, pyroptosis and its underlying immunological features are to blame for the onset and progression of IPF. PRG-based predictive models and drugs may offer new treatment options for IPF.

A ratiometric fluorescent probe for imaging the fluctuation of HOBr during endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress is closely associated with cell apoptosis, autophagy, DNA damage, metabolism, and migration. When ER stress occurs, a large number of reactive oxygen species, including hypobromous acid (HOBr), are generated. The degree of ER stress can be understood by accurately detecting the HOBr concentration in the ER. Unfortunately, no ER-targetable probes for detecting HOBr have been reported to date. To solve this problem, we developed a naphthalimide-based fluorescent probe (ER-NABr) for imaging HOBr in the ER. Upon reaction with HOBr, a red shift in the fluorescence spectrum occurs due to the difference in the molecular conjugation between the original ER-NABr and the reaction product. ER-NABr showed a fast response (within 30 s) and high selectivity towards HOBr, with a ratiometric quantitative response (5-40 µM) and high sensitivity (138 nM). With its excellent biocompatibility and remarkable ER-targetable ability, ER-NABr was successfully utilized to ratiometrically image intracellular HOBr, particularly during ER stress, which is beneficial for revealing the role of HOBr in ER-associated diseases.

Self-Reinforced Piezoelectric Response of an Electroluminescent Film for the Dual-Channel Signal Monitoring of Damaged Areas.

Organic piezoelectric nanogenerators (PENGs) show promise for monitoring damage in mechanical equipment. However, weak interfacial bonding between the reinforcing phase and the fluorinated material limits the feedback signal from the damaged area. In this study, we developed a PENG film capable of real-time identification of the damage location and extent. By incorporating core-shell barium titanate (BTO@PVDF-HFP) nanoparticles, we achieved enhanced piezoelectric characteristics, flexibility, and processability. The composite film exhibited an expanded output voltage range, reaching 41.8 V with an increase in frequency, load, and damage depth. Additionally, the film demonstrated self-powered electroluminescence (EL) during the wear process, thanks to its inherent ferroelectric properties and the presence of luminescent ZnS:Cu particles. Unlike conventional PENG electroluminescent devices, the PENG film exhibited luminescence at the damage location over a wide temperature range. Our findings offer a novel approach for realizing modular and miniaturized real-time damage mapping systems in the field of safety engineering.

Catalysts and electrolyzers for the electrochemical CO2 reduction reaction: from laboratory to industrial applications.

To cope with the urgent environmental pressure and tight energy demand, using electrocatalytic methods to drive the reduction of carbon dioxide molecules and produce a variety of fuels and chemicals, is one of the effective pathways to achieve carbon neutrality. In recent years, many significant advances in the study of the electrochemical carbon dioxide reduction reaction (CO2RR) have been made, but most of the works exhibit low current density, small electrode area and poor long-term stability, which are not suitable for large-scale industrial applications. Herein, combining the research achievements obtained in laboratories and the practical demand of industrial production, we summarize recent frontier progress in the field of the electrochemical CO2RR, including the fundamentals of catalytic reactions, catalyst design and preparation, and the construction of electrolyzers. In addition, we discuss the bottleneck problem of industrial CO2 electrolysis, and further present the prospect of the essential issues to be solved by the available technology for industrial electrolysis. This review can provide some basic understanding and knowledge accumulation for the development and practical application of electrochemical CO2RR technology.

Phototherapy for age-related brain diseases: Challenges, successes and future.

Brain diseases present a significant obstacle to both global health and economic progress, owing to their elusive pathogenesis and the limited effectiveness of pharmaceutical interventions. Phototherapy has emerged as a promising non-invasive therapeutic modality for addressing age-related brain disorders, including stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), among others. This review examines the recent progressions in phototherapeutic interventions. Firstly, the article elucidates the various wavelengths of visible light that possess the capability to penetrate the skin and skull, as well as the pathways of light stimulation, encompassing the eyes, skin, veins, and skull. Secondly, it deliberates on the molecular mechanisms of visible light on photosensitive proteins, within the context of brain disorders and other molecular pathways of light modulation. Lastly, the practical application of phototherapy in diverse clinical neurological disorders is indicated. Additionally, this review presents novel approaches that combine phototherapy and pharmacological interventions. Moreover, it outlines the limitations of phototherapeutics and proposes innovative strategies to improve the treatment of cerebral disorders.

Astragaloside IV Alleviates Depression in Rats by Modulating Intestinal Microbiota, T-Immune Balance, and Metabolome.

This study aims to explore the effects of Astragaloside IV (AS-IV) on abnormal behaviors, intestinal microbiota, intestinal T-immune balance, and fecal metabolism of a model of depression in rats. Herein, we integrally applied 16S rRNA sequencing, molecular biological techniques, and 1H NMR-based fecal metabolomics to demonstrate the antidepression activity of AS-IV. The results suggested that AS-IV regulated the depression-like behaviors of rats, which are presented by an increase of body weight, upregulation of sucrose preference rates, and a decrease of immobility time. Additionally, AS-IV increased the abundances of beneficial bacteria (Lactobacillus and Oscillospira) in a model of depression in rats. Moreover, AS-IV regulated significantly the imbalance of Th17/Treg cells, and the abnormal contents of both anti-inflammatory factors and pro-inflammatory factors. Besides, fecal metabolomics showed that AS-IV improved the abnormal levels of short-chain fatty acids and amino acids. Collectively, our research supplemented new data, supporting the potential of AS-IV as an effective diet or diet composition to improve depression-like behaviors, dysfunctions of microbiota, imbalance of T immune, and the abnormality of fecal metabolome. However, the causality of the other actions was not proven because of the experimental design and the methodology used. The current findings suggest that AS-IV could function as a promising diet or diet composition to alleviate depressed symptoms.