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Abstract In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the ‘golden chamber’ medical text, Huangdi Neijing, diabetes mellitus falls under the category ‘collateral disease’. TCM, with its wealth of experience, has been treating diabetes for over two millennia. Different antidiabetic Chinese herbal medicines reduce blood sugar, with their effective ingredients exerting unique advantages. As well as a glucose lowering effect, TCM also regulates bodily functions to prevent diabetes associated complications, with reduced side effects compared to western synthetic drugs. Chinese herbal medicine is usually composed of polysaccharides, saponins, alkaloids, flavonoids, and terpenoids. These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion, enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals. These actions regulate glycolipid metabolism in the body, eventually achieving the goal of normalizing blood glucose. Using different animal models, a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer. Nonetheless, there is a dearth of scientific data about the pharmacology, dose‐effect relationship, and structure–activity relationship of TCM and its constituents. Further research into the efficacy, toxicity and mode of action of TCM, using different metabolic and molecular markers, is key to developing novel TCM antidiabetic formulations.

Abstract Background Salvia miltiorrhiza Bunge, a significant and widely used medicinal herb, is also recognized in the US Pharmacopoeia as a dietary supplement. However, the decline in yield and quality limits its further development as a traditional herbal medicine. Therefore, a deeper understanding of how synthetic communities (SynCom) affect the quality and yield of S. miltiorrhiza and the underlying mechanisms is necessary. Results In this study, we selected S. miltiorrhiza as the research subject and designed two synthetic communities (SynCom 1 and SynCom 2) using five endophytic fungi without significantly growth-promoting effect. We conducted both greenhouse and field experiments to investigate their impact on the yield and quality of the herbal plants. Greenhouse experiments confirmed that SynCom 1 significantly increased the biomass of S. miltiorrhiza, whereas SynCom 2 had the opposite effect. Field experiments further demonstrated that the application of SynCom 1 promoted photosynthesis and enhanced carbon and nitrogen metabolism, steady and markedly promoted plant growth, and thus increased S. miltiorrhiza yield compared to the uninoculated. In contrast, SynCom 2 inhibited yield but increased the content of the main active components. Un-targeted metabolomics analysis showed that SynCom 1 mainly promoted tricarboxylic acid cycle and nitrogen assimilation process to increase yield, and SynCom 2 mainly increase substrate content in the salvianolic acid and tanshinone synthesis pathways to improve quality. Conclusion These beneficial qualities exhibited by SynComs composed of fungi without apparent growth-promoting abilities represent an untapped resource that can be leveraged to enhance crop productivity. This opens up new research avenues for precision manipulation of plant microbiomes. Graphical abstract

Abstract This study aimed to evaluate arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb) levels in dried chili peppers from nine districts in Guizhou Province. These heavy metals, widely dispersed and capable of transferring to crops, pose potential health risks to humans. The assessment included modeling daily intake (EDI), target hazard quotient (THQ), total target hazard index (TTHQ), and target carcinogenic risk (TCR) to assess health risks across different population groups. Results showed chromium (0.9540 ± 0.301 mg/kg) and lead (0.8949 ± 0.266 mg/kg) had the highest concentrations, followed by arsenic (0.3287 ± 0.093 mg/kg) and cadmium (0.0627 ± 0.017 mg/kg). Children exhibited higher EDI values than adults, indicating greater health risks from dried chili pepper consumption at equivalent levels. THQ and TTHQ values were below 1 across all regions, indicating no significant health risks associated with dried chili pepper consumption. Similarly, TCR values were below 10–4 for all nine regions, indicating an acceptable level of carcinogenic risk. Overall, consuming dried chili peppers in Guizhou Province poses an acceptable health risk, but caution is advised, especially for children, to limit heavy metal exposure.

Abstract Background The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. Methods A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 106 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. Results The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. Conclusions Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.

Abstract Background Cardiometabolic multimorbidity (CMM) is a growing global health problem, and obstructive sleep apnea (OSA) is recognized as an important risk factor for cardiovascular disease. However, the impact of OSA on the prognosis of CMM patients remains unclear. Methods This study was a sub-study of OSA-acute coronary syndrome (ACS) and included 1, 927 hospitalized ACS patients. Patients were divided into the CMM group and the non-CMM group. OSA was diagnosed using the apnea-hypopnea index (AHI). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint included cardiac events, all-cause death and all repeat revascularizations. Results This study enrolled 1, 927 patients hospitalized for ACS, with a median follow-up of 3 years. Among them, 723 patients (37.5%) had CMM, while 1, 204 patients (62.5%) did not have CMM. Over half of the patients in each group had OSA. OSA patients exhibited worse cardiometabolic profiles than their non-OSA counterparts, including higher body mass index (BMI), glycemic indices, lipids and inflammation. In the CMM group, OSA patients had a significantly higher incidence of MACCE than non-OSA patients (34.7% vs. 23.7%, p = 0.004). These results remained significant after adjustment, indicating that OSA substantially increased the risk of MACCE in the CMM group (adjusted hazard ratio [HR]: 1.432; 95% confidence interval [CI]: 1.017–2.016; p = 0.040). Conversely, the incidence of MACCE was similar between OSA and non-OSA subgroups within the non-CMM cohort. Subgroup analyses showed that OSA increased the risk of MACCE in CMM patients aged ≥ 60 years (adjusted HR: 1.642; 95% CI: 1.031–2.615; p = 0.037) and in those with specific clinical characteristics. Conclusion OSA significantly impacts the prognosis of CMM patients, highlighting the need for targeted OSA screening and management strategies to improve outcomes in this population potentially.

Abstract Background Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. Methods We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. Results Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. Conclusion The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

Sapphire exhibits typical anisotropy due to its unique crystal structure, and there are significant property differences in different processing areas during the machining of curved sapphire component, making it essential to investigate the anisotropy in the removal process of sapphire materials for efficient curved surface machining. In this study, the force and acoustic emission (AE) signals were monitored at different scratch stages and orientations, and the anisotropic characteristics of ductile-brittle transition (DBT) depths, material removal morphology, and subsurface crack propagation direction were analyzed. The results indicate that the anisotropy of force signals and DBT depths is mainly reflected in the differences between crystal planes. In addition, the removal morphology of materials with different crystal orientations showed smooth scratch grooves with unclear anisotropic characteristics during the ductile removal (DR) stage, while the crack propagation direction with different scratch orientations during the DBT stage showed significant anisotropic characteristics. The brittle removal (BR) stage is characterized by brittle spalling in the form of shell-like, blocky, and fishbone spalling, and there is a significant anisotropic difference in the spalling shapes on both sides of the scratch. The original AE signals, Fast Fourier Transform (FFT), and Short Time Fourier Transform (STFT) results show that the AE frequencies of different crystal planes are different, and the differences in different scratch orientations on the same crystal plane are reflected in the peak amplitude. Finally, the propagation directions of subsurface cracks with different directions are anisotropic due to different scratching crystal planes, and propagate mainly along directions of 15°, 29°, 32°, 58°, and 105°.

Abstract Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level. Graphical Abstract

Abstract Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.

Abstract Background Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. Methods The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). Results HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. Conclusions HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.

0Cr16Ni5Mo1 super martensitic stainless steel has excellent weldability and is an economical material with a high life cycle and low cost, but there are few researches and applications of this material in additive manufacturing. In order to realize the application of 0Cr16Ni5Mo1 large-area laser cladding technology, the multi-track lap cladding of the material was studied. In this work, a multi-physical finite element model of multi-layer multi-track laser cladding was established, taking into account thermodynamic processes such as phase transition, Marangoni convection, and buoyancy. The flow and heat transfer behavior of 0Cr16Ni5Mo1 in multi-layer multi-track laser cladding process and the characteristics of the molten pool are studied. The research focused on the flow heat transfer behavior and molten pool characteristics of 0Cr16Ni5Mo1 during multi-layer multi-track laser cladding. The discussed aspects include the evolution history of the temperature field within the molten pool, flow field characteristics, molten pool dimensions, and dilution ratio under various laser powers and overlap rates. The results show that with the increase of overlap rate, the morphology of molten pools in different clad tracks will also change, and the flow rate, dilution ratio, and length of molten pools in the second track are negatively correlated, while the temperature and height of molten pools are positively correlated. As the laser power increases, all the characteristic quantities are positively correlated with it.

Background Systemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters. Methods Comparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes. Results SLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses. Conclusion The signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.

Abstract A kind of all‐dielectric circularly polarised (CP) loop antenna made of high‐permittivity material is proposed. The leaky‐wave radiation from a high‐permittivity dielectric waveguide is utilised here to support the operation of the proposed antenna. A non‐closed dielectric loop covering a three‐quarter circle is adopted to generate CP radiation and it is connected with the dielectric ground via one of bending ends to form an all‐in‐one structure of the antenna. The other end is also bent and vertical to the ground, but hanging in the air for probe feed. As two kinds of typical high‐permittivity dielectric materials, zirconia ceramic and pure water are used to implement the proposed design respectively. On one hand, an all‐ceramic CP loop antenna made of zirconia is proposed. And benefiting from the low loss and high melting point of zirconia, the proposed ceramic antenna has superiority in radiation efficiency and could adapt to a harsh environment. On the other hand, by using pure water and transparent container, a fully‐transparent CP water loop antenna can be obtained. Finally, a 3‐D printing technology is adopted in the manufacturing of ceramic structure and resin container. Measured results of both antennas demonstrate the validity of the proposed design.

Abstract Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ferroptosis is controversial and the value of the interaction between BRD4 inhibitors and ferroptosis inducers remains to be explored. Here, we found that BRD4 inhibition greatly enhanced erastin-induced ferroptosis in different types of cells, including HEK293T, HeLa, HepG2, RKO, and PC3 cell lines. Knocking down BRD4 in HEK293T and HeLa cells also promoted erastin-induced cell death. BRD4 inhibition by JQ-1 and I-BET-762 or BRD4 knockdown resulted in substantial accumulation of reactive oxygen species (ROS) in both HEK293T and HeLa cells. The effect of BRD4 inhibition on ferroptosis-associated genes varied in different cells. After using BRD4 inhibitors, the expression of FTH1, Nrf2, and GPX4 increased in HEK293T cells, while the levels of VDAC2, VDAC3, and FSP1 decreased. In HeLa cells, the expression of FTH1, VDAC2, VDAC3, Nrf2, GPX4, and FSP1 was reduced upon treatment with JQ-1 and I-BET-762. Consistently, the level of FSP1 was greatly reduced in HEK293T and HeLa cells with stable BRD4 knockdown compared to control cells. Furthermore, ChIP-sequencing data showed that BRD4 bound to the promoter of FSP1, but the BRD4 binding was greatly reduced upon JQ-1 treatment. Our results suggest that ROS accumulation and FSP1 downregulation are common mechanisms underlying increased ferroptosis with BRD4 inhibitors. Thus, BRD4 inhibitors might be more effective in combination with ferroptosis inducers, especially in FSP1-dependent cancer cells.

As exemplified by the COVID-19 pandemic, the design and implementation of data-driven health surveillance, like digital contact tracing (DCT) apps, carry significant implications for society. However, its rushed development calls for careful consideration from all involved stakeholders to achieve a shared understanding and engage in joint-sensemaking in order to implement DCT collaboratively and effectively utilize it in the fight against the pandemic. Yet, the empirical ground truth and theoretical mechanism of joint-sensemaking are both unclear. Drawing on this gap, this article applies a multistep approach, including sentiment analysis, topic analysis coupled with regression and unique network analysis, to thoroughly explore, examine, and explain the dynamic process of joint-sensemaking in the context of a public crisis. Based on evidence from 113,264 Weibo posts, we illustrate two joint-sensemaking pathways and three key interventions using the case of China's Health Code in the context of the DCT. We reveal that the effectiveness of different interventions and contributions made by stakeholders vary significantly between different joint-sensemaking pathways. Specifically, we find that official media and opinion leaders act as crucial mediators in bridging intervention conductors and the public. However, their influence presents heterogeneity toward different network modularity, thus leading to distinct patterns. Additionally, inconsistent with previous literature, we find that within the context of the China Health Code, official media has a greater impact on opinion leaders in engaging the public.

Cardiotoxicity is a common side effect of cisplatin in cancer treatment, often complicating patient care. Tangeretin (TG), a natural compound found in citrus peel, shows promise in protecting against cisplatin-induced heart damage. Our study investigated TG’s protective effects both in cell culture and in animal models. TG effectively countered cisplatin-induced damage in heart cells, promoting mitochondrial health and glucose transporter expression. In animal studies, TG reduced markers of heart damage and improved cardiac function. Mechanistically, TG activated AMPK, reduced the inactivation of Acetyl-CoA Carboxylase (ACC) protein and inhibited p38 MAPK and prevented mitochondrial dysfunction and cell death. This research sheds light on TG’s potential in safeguarding the heart from cisplatin-induced harm.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Aims: To identify and analyze genes closely related to the progression of nonalcoholic steatohepatitis (NASH) by employing a combination of single-cell RNA sequencing and machine-learning algorithms. Main methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed to find the cell population with the most significant differences between the Chow and NASH groups. This approach was used to validate the developmental trajectory of this cell population and investigate changes in cellular communication and important signaling pathways among these cells. Subsequently, high dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) was used to find the key modules in NASH. Machine learning analyses were performed to further identify core genes. Deep learning techniques were applied to elucidate the correlation between core genes and immune cells. The accuracy of this correlation was further confirmed using deep learning techniques, specifically Convolutional Neural Networks. Key findings: By comparing scRNA-seq data between the Chow and NASH groups, we have observed a notable distinction existing in the Kupffer cell population. Signaling interactions between hepatic macrophages and other cells were significantly heightened in the NASH group. Through subsequent analysis of macrophage subtypes and key modules, we identified 150 genes tightly associated with NASH. Finally, we highlighted the 16 most significant core genes using multiple iterations of machine learning. Furthermore, we pointed out the close relationship between core genes and immune cells. Significances: Using scRNA-seq analysis and machine learning, we can distinguish NASH-related genes from large genetic datasets, providing theoretical support in finding potential targets for the development of novel therapies.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3−/− mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

AbstractAlismataceae is one of the early diverged families of monocotyledonous plants. We report the complete chloroplast genomes of three Alisma species, including Alisma orientale (Sam.) Juzep. 1934, A. subcordatum Raf. 1908, and A. triviale Pursh 1813, of which A. orientale is a traditional Chinese medical plant used widely to treat diuretics, diabetes, hepatitis, and inflammation. We sequenced the complete chloroplast genomes with the Illumina Nova-Seq 6000 platform using herbarium collections. The chloroplast genomes of A. orientale, A. subcordatum and A. triviale are 159,861 bp, 160,180 bp, and 159,727 bp in length, respectively. The three chloroplast genomes each contain 113 genes, including four rRNAs, 30 tRNAs genes, and 79 protein-coding genes, and the average GC content is 36.0%. Based on the whole chloroplast genomes of 19 species of Alismataceae and the close allies, the medicinally important A. orientale was found to be closely related to another medicinal plant Alisma plantago-aquatica L. 1753 in the phylogenetic analysis. The genus Alisma was supported to be monophyletic.

Abstract CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.