Progression from cardiomyopathy to heart failure with reduced ejection fraction: A CORIN deficient course.

Cardiomyopathies, encompassing hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), constitute a diverse spectrum of heart muscle diseases that often culminating in heart failure (HF). The inherent molecular heterogeneity of these conditions has implications for prognosis and therapeutic strategies. Publicly available microarray and RNA sequencing (RNA-seq) data sets of HCM (n = 106 from GSE36961) and DCM (n = 18 from GSE135055 and 166 from GSE141910) patients were employed for our analysis. The Non-negative Matrix Factorization (NMF) algorithm was applied to explore the molecular stratification within HCM and DCM, and enrichment analysis was performed to delineate their biological characteristics. By integrating bulk and single-nucleus RNA-seq (snRNA-seq) data, we identified a potential biomarker for HCM progression and cardiac fibrosis, which was subsequently validated using mendelian randomization and in vitro. Our application of NMF identified two distinct molecular clusters. Particularly, a profibrotic, heart failure with reduced ejection fraction (HFrEF)-resembling Cluster 1 emerged, characterized by diminished expression of CORIN and a high degree of fibroblast activation. This cluster also exhibited lower left ventricular ejection fraction (LVEF) and worse prognostic outcomes, establishing the significance of this molecular subclassification. We further found that overexpression of CORIN could mitigate TGFß1-induced expression of col1a1 and α-SMA in neonatal rat cardiac fibroblasts. Our results indicated the heterogeneity of HCM population, and further evidenced the participation of corin in the progression of HCM, DCM and HFrEF. Nevertheless, our study is constrained by the lack of corresponding clinical data and experimental validation of the identified subtypes. Therefore, further studies are warranted to elucidate the downstream pathways of corin and to validate these findings in independent patient cohorts.

LiLnGeS4 (Ln = La-Nd): Designing High Performance Infrared Nonlinear Optical Sulfides through "Band Reformation of AGS".

AgGaS2 (AGS) is the most commonly used commercial infrared nonlinear optical material. However, AGS has a narrow band gap (Eg = 2.58 eV) and a low laser-induced damage threshold (LIDT), primarily attributed to its mobile liquid-like Ag+ constituent and the unstable Ag-S chemical bond. Herein, we propose a "band reformation of AGS" strategy, which leads to the success syntheses of four lanthanide sulfides, LiLnGeS4, crystalizing in an asymmetric Ama2 structure. LiLaGeS4 demonstrates that eliminating the presence of Ag-4d band increases the Eg to 3.32 eV and enhances the LIDT (14-29 × AGS, measured by both powder and single crystal); while increasing the nonbonding density of states of the S-3p band enhances the 2nd-nonlinear optical coefficient (1.06 × AGS). Besides, the bond length discrepancy between [LiS4], [GeS4] and [LaS8] units leads to a moderate birefringence (Δn = 0.052). Such a unique structure further results in extremely small thermal expansion with αL = 0.41-1.74 × 10-5 K-1, along different crystallographic axes. Our theoretical studies indicate that the synergy of the structure building units contribute to the second harmonic generation performance. These results suggest that the "band reformation of AGS" strategy provides effective guidance to discover new NLO crystals with optimized performance.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases.

BACKGROUND: Evaluating the psychological resilience of lung cancer (LC) patients helps understand their mental state and guides future treatment. However, there is limited research on the psychological resilience of LC patients with bone metastases. AIM: To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience. METHODS: LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University. The psychological scores of the enrolled patients were collected. They were then grouped based on the mean psychological score: Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group. The baseline data (age, gender, education level, marital status, residence, monthly income, and religious beliefs), along with self-efficacy and medical coping mode scores, were compared. RESULTS: This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023, with an average psychological resilience score of 63.24 ± 9.96 points. After grouping, the low-score group consisted of 69 patients, including 42 males and 27 females, with an average age of 67.38 ± 9.55 years. The high-score group consisted of 73 patients, including 49 males and 24 females, with a mean age of 61.97 ± 5.00 years. χ 2 analysis revealed significant differences between the two groups in education level (χ 2 = 6.604, P = 0.037), residence (χ 2 = 12.950, P = 0.002), monthly income (χ 2 = 9.375, P = 0.009), and medical coping modes (χ 2 = 19.150, P = 0.000). Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores (t = 3.383, P = 0.001) and lower age than the low-score group (t = 4.256, P < 0.001). Furthermore, multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience [odds ratio (OR) = 0.926, P = 0.035, 95% confidence interval (CI): 0.862-0.995], while age (OR = 1.099, P = 0.003, 95%CI: 1.034-1.169) and medical coping modes (avoidance vs confrontation: OR = 3.767, P = 0.012, 95%CI: 1.342-10.570; resignation vs confrontation: OR = 5.687, P = 0.001, 95%CI: 1.974-16.385) were identified as independent risk factors. A predictive model based on self-efficacy, age, and medical coping modes was developed. The receiver operating characteristic analysis showed an area under the curve value of 0.778 (95%CI: 0.701-0.856, P < 0.001), indicating that the model has good predictive performance. CONCLUSION: LC patients with bone metastases are less psychologically resilient than the general population. Factors such as self-efficacy, age, and medical coping modes influence their psychological resilience. Patients with low self-efficacy, old age, and avoidance/resignation coping modes should be closely observed.

New record of Miniopterusmagnater (Chiroptera, Miniopteridae) from south-western China and a comparative study of three species of Miniopterus in China.

Background: This research documents a new record of Miniopterusmagnater in the south-western region of China, a significant discovery given the limited diversity of the Miniopterus genus within the country. Only three species of Miniopterus occur in China: Miniopterusmagnater, Miniopterusfuliginosus and Miniopteruspusillus. These species share a high degree of morphological similarity, particularly in their external characteristics. This underscores the necessity for the identification of additional distinguishing traits that can aid in the taxonomic differentiation of these closely-related species. New information: During the 2023 field expedition to various nature reserves in Yunnan Province, China, we encountered specimens of the genus Miniopterus. Utilising a combination of morphological assessments and phylogenetic analyses, we identified six individuals as Miniopterusmagnater. A review of the existing geographical distribution data revealed that this species is primarily found in central and southern regions of China, with no previous records from the south-western part of the country. Based on our findings, we present a novel record of Miniopterusmagnater's distribution in the south-western region of China.

Extract of Tinospora sinensis alleviates LPS-induced neuroinflammation in mice by regulating TLR4/NF-κB/NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rattan stem of Tinospora sinensis (Lour.) Merr. is valued for its efficacy of clearing heat and removing toxicity, calming and soothing the nerves. It is widely used in Tibetan medicine for the treatment of rheumatic and aging diseases. Studies have confirmed its anti-inflammatory and ameliorating effects on Alzheimer's disease; however, the anti-neuroinflammation efficacy and mechanism remain unclear. AIM: This study aimed to explore the anti-neuroinflammation efficacy, major effective ingredients, and potential mechanism of extract of Tinosporae sinenisis (TIS). METHODS: UPLC-Q-TOF/MS was used to identify the compounds of TIS and the plasma components of rats after gastric administration of TIS. C57BL/6 J mice were continuously intraperitoneally injected with lipopolysaccharide (LPS) (250 µg/kg) for 14 d to establish a neuroinflammation model. The effects of TIS (4.5 g/kg, 9 g/kg) on the learning and memory abilities in mice with neuroinflammation was evaluated using spontaneous activity, novel object recognition, and Morris water maze tests. Pathological changes in the hippocampus were observed using hematoxylin and eosin staining. Gene and protein levels of inflammatory factors in the brain were detected using qRT-PCR and ELISA kits. Iba-1 levels in the brain were detected using immunofluorescence to assess the degree of microglial activation. Network pharmacology, based on the components absorbed into plasma of TIS, was used to predict potential targets and pathways. Proteomics was used to study the differentially expressed proteins and related pathways in the brain tissue of mice with neuroinflammation. Finally, correlation analysis was performed on the results of network pharmacology and proteomics, and proteins related the anti-neuroinflammatory effect of TIS were detected by western blot. RESULTS: A total of 39 compounds were identified in TIS: genipingentiobioside, isocorydin, reticuline, (-)-argemonine, tinosineside A, tinosinenside A, and costunolide were absorbed into the plasma. After continuous intraperitoneal injection of LPS into C57BL/6 J mice, microglia in the brain tissue were activated and the gene and protein levels of IL-1ß, TNF-α, IL-6, and iNOS were increased in the brain tissue, suggesting that the neuroinflammation model was successfully established. TIS reduced Iba-1 levels and gene expression and protein levels of inflammatory factors in the brain of mice with neuroinflammation. Furthermore, TIS improved the pathological changes in the hippocampus and learning and memory abilities caused by neuroinflammation. Network pharmacology has predicted that TNF, IL-1ß, and IκBKB are closely related to neuroinflammation. Proteomics identified key differentially expressed proteins, including TNF, NF-κB2, NF-κBIA, and TLR4. Toll-like receptor (TLR), NF-κB, and NOD-like receptor (NLR) signaling pathways are involved in neuroinflammation-related pathways. Correlation analysis revealed TLR, TNF and NLR signaling pathways were closely related to the anti-neuroinflammatory effects of TIS. We observed that TIS alleviated neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 pathway. CONCLUSION: Thirty-nine compounds were identified from TIS, among which seven were absorbed into the plasma as prototype components. TIS alleviated LPS-induced neuroinflammation in mice, and its mechanism was related to inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Effect of ART treatments on maternal and neonatal outcomes in singleton live births: A large-scale retrospective cohort study.

Background: The increased risk of pregnancy complications in the ART population has been reported, but the source of these risks remains controversial. The study aims to evaluate the association between ART treatments and patient characteristics with maternal and neonatal outcomes. Methods: This was a retrospective analysis of 45,159 singleton pregnant women at a hospital between 2018 and 2021. The maternal and neonatal outcomes included pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), placental abruption (PA), placenta accreta spectrum (PAS), postpartum hemorrhage (PPH), cesarean section, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), low birth weight (LBW), macrosomia, and birth defects. We assessed the outcomes among the fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception (SC) groups. Potential risk factors were further analyzed in the ART population. Results: FET was associated with higher risks for PIH (SC: AOR, 1.97(1.51-2.57); fresh ET: AOR, 1.68(1.03-2.72)), PE (SC: 2.28(1.86-2.80); fresh ET: AOR, 1.61(1.11-2.33)), PAS (SC: AOR, 3.89(3.39-4.46); fresh ET: AOR, 2.23(1.70-2.92)), PPH (SC: AOR, 3.46(2.76-4.34)); fresh ET: 2.09(1.39-3.14)), and macrosomia (SC: 1.53(1.25-1.86); fresh ET: AOR, 2.87(1.89-4.35). Fresh ET was associated with higher risks for PA (SC: AOR, 2.19(1.51-3.18); FET: AOR, 0.39(0.17-0.90)), SGA (SC: AOR, 1.56(1.06-2.31), FET: AOR, 0.42(0.19-0.91)), and LBW (SC: AOR, 2.24(1.82-2.77), FET: AOR, 0.63 (0.44-0.89)), and fresh ET is an independent risk factor for PA and SGA. Furthermore, the risk of GDM was associated with the biological characteristic of low-fertility patients. Conclusions: Embryo status (fresh or frozen) is a key factor affecting the maternal and neonatal outcomes in ART treatments, while biological characteristics of infertile patients also play a certain role.

CCDC181 is required for sperm flagellum biogenesis and male fertility in mice.

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

A tellurium-based small compound ameliorates tumor metastasis by downregulating heparanase expression.

Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) is the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory and can modulate types of cytokines. However, the effect of AS101 on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains of proteoglycans on the cell surface, further leading to the degradation of the extracellular matrix. Heparanase also releases angiogenic factors in the extracellular matrix, is overexpressed in tumor cells, and promotes tumor metastasis and angiogenesis. In this study, we investigated the effect of AS101 in 4T1 and CT26 cells, especially heparanase. Heparanase expression was downregulated in 4T1 and CT26 cells after treatment with AS101 in vitro. The protein level involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway also declined. Cell migration assays revealed the inhibitory effect of AS101 on migration. The results of this study indicate that AS101 inhibits tumor migration by downregulating heparanase through the AKT/mTOR signaling pathway and has positive effects in vivo.

Laparoscopy combined with hysteroscopy in the treatment of Robert's uterus accompanied by adenomyosis: A case report.

BACKGROUND: Gynaecologists should be aware of a rare obstructive Mullerian duct abnormality like Robert's uterus and perform further surgery when necessary. CASE SUMMARY: We report a 41-year-old mother of two children with Robert's uterus who was examined and treated by laparoscopy and hysteroscopy. Unlike the existing cases reported in the literature, this patient had a late onset of Robert's uterus symptoms. Due to right tubal ectopic pregnancy 3 years previously, the patient was treated with right salpingectomy and left tubal ligation but suffered aggravated left lower abdominal pain. She was examined and treated by laparoscopy and hysteroscopy, and is completely asymptomatic at 5-year follow-up. CONCLUSION: The typical obstructive Mullerian abnormality requires further surgery. Combined laparoscopy and hysteroscopy is an effective, minimally invasive technique with better recovery outcomes than traditional transabdominal procedures.

CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023).

Background: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported. Methods: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs). Results: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%). Conclusion: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.

Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.

BACKGROUND: Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. METHODS: Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. RESULTS: The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. CONCLUSIONS: Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Widely Targeted Lipidomics and Microbiomics Perspectives Reveal the Mechanism of Auricularia auricula Polysaccharide's Effect of Regulating Glucolipid Metabolism in High-Fat-Diet Mice.

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders.

Dahuang Zhechong Pill Improves Pulmonary Fibrosis through miR-29b-2-5p/HK2 Mediated Glycolysis Pathway.

OBJECTIVE: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms. METHODS: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-ß 1 (TGF-ß 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-ß 1, TGF-ß 1+10% DMS, TGF-ß 1+10% DMS+miR-29b-2-5p inhibitor, TGF-ß 1+10% DMS+inhibitor negative control, TGF-ß 1+10% DMS+miR-29b-2-5p mimic and TGF-ß 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA. RESULTS: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01). CONCLUSIONS: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis.

An ensemble deep learning model for predicting minimum inhibitory concentrations of antimicrobial peptides against pathogenic bacteria.

The rise of antibiotic resistance necessitates effective alternative therapies. Antimicrobial peptides (AMPs) are promising due to their broad inhibitory effects. This study focuses on predicting the minimum inhibitory concentration (MIC) of AMPs against whom-priority pathogens: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. We developed a comprehensive regression model integrating AMP sequence-based and genomic features. Using eight AI-based architectures, including deep learning with protein language model embeddings, we created an ensemble model combining bi-directional long short-term memory (BiLSTM), convolutional neural network (CNN), and multi-branch model (MBM). The ensemble model showed superior performance with Pearson correlation coefficients of 0.756, 0.781, and 0.802 for the bacterial strains, demonstrating its accuracy in predicting MIC values. This work sets a foundation for future studies to enhance model performance and advance AMP applications in combating antibiotic resistance.

Effect of heat pump drying temperature on moisture migration characteristics and quality of instant Tremella fuciformis.

Low-field nuclear magnetic resonance (LF-NMR) was used to analyze the moisture migration characteristics and water distribution of instant Tremella fuciformis (ITF) during heat pump drying at 35 °C, 45 °C and 55 °C. A fuzzy mathematical evaluation method was then used to investigate the effect of heat pump drying temperatures (35 °C, 45 °C and 55 °C) on the quality of ITF. Based on the screened appropriate temperature of 45 °C, the thin layer heat pump drying curve and drying rate curve of ITF were drawn, then four mathematical models were tested based on the coefficient of determination (R2). The result showed three water components (bound water (T 21), immobilized water (T 22), and free water (T 23)) in ITF before drying. During the drying process, the heat pump drying of ITF was carried out gradually from the outer to the inner. The sensory total score (77.66 ± 6.57), rehydration ratio (4803.00 ± 90.00%), and viscosity (45.01 ± 3.61 Pa s) of ITF in heat pump drying at 45 °C were the best. The optimal drying temperature of 45 °C was obtained by the fuzzy comprehensive evaluation with the highest comprehensive score of 77.85%. With the prolongation of drying time, the water content of ITF showed a gradual decreasing trend, and the water content was controlled to below 8.51% after 6 h. The drying curve shows that the drying phase of the ITF is divided into three phases, including preheat, constant speed and deceleration. The drying speed first increases, remains constant in the middle and then decreases. Among the four models tested, the cubic regression equation aligned with the change rule of the ITF drying curve (R2 = 0.99397). By studying the effect of drying temperature on the moisture migration characteristics and the quality of ITF, we aim to provide more data support for the production of T. fuciformis.

From Skin to Gut: Understanding Microbial Diversity in Rana amurensis and R. dybowskii.

Amphibians face the threat of decline and extinction, and their health is crucially affected by the microbiota. Their health and ecological adaptability essentially depend on the diverse microbial communities that are shaped by unique host traits and environmental factors. However, there is still limited research on this topic. In this study, cutaneous (C) and gut (G) microbiota in Rana amurensis (A) and R. dybowskii (D) was analyzed through 16S amplicon sequencing. Groups AC and DC significantly differed in alpha diversity, while the gut groups (AG and DG) showed no such differences. Analyses of Bray-Curtis dissimilarity matrix and unweighted UniFrac distances showed significant differences in cutaneous microbiota between groups AC and DC, but not between groups AG and DG. Stochastic processes significantly influenced the assembly of cutaneous and gut microbiota in amphibians, with a notably higher species dispersal rate in the gut. The predominant phyla in the skin of R. amurensis and R. dybowskii were Bacteroidetes and Proteobacteria, respectively, with significant variations in Bacteroidota. Contrarily, the gut microbiota of both species was dominated by Firmicutes, Proteobacteria, and Bacteroidetes, without significant phylum-level differences. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial enrichment in each group. Predictive analysis using phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) revealed the significant functional pathways associated with the microbiota, which indicates their potential roles in immune system function, development, regeneration, and response to infectious diseases. This research underscores the critical impact of both host and environmental factors in shaping amphibian microbial ecosystems and emphasizes the need for further studies to explore these complex interactions for conservation efforts.

Multifunctional SERS Substrate for Simultaneous Detection of Multiple Contaminants and Photothermal Removal of Pathogenic Bacteria.

In this work, a boric-acid-modified Fe3O4@Au@BA-MOF composite material as a multifunctional SERS substrate was ingeniously constructed for detecting both pathogens and antibiotics as well as photothermally inactivating the pathogens. Through improving the dispersity and stability of gold nanoparticles (Au NPs), leveraging the specificity of boric acid (BA) groups in recognizing cis-diol structures, and the ability of SERS technology to provide unique fingerprint spectra of targets, the sensitive and stable detection of pathogens and antibiotics was achieved. Compared with Au NPs and Fe3O4@Au, the SERS enhancement factor of Fe3O4@Au@BA-MOF was 4.31 × 106, which was about 400 times and 16 times higher than the former two, respectively. Among the existing work, the limit of detection for pathogens was lower or comparable, and it exhibited good stability, maintaining consistent performance for 23 days. Additionally, this substrate achieved efficient photothermal inactivation of pathogens under both near-infrared light and natural light excitation. Within 8 min of near-infrared light irradiation, the bactericidal rates for Staphylococcus aureus and Escherichia coli reach 100% and 99.3%, respectively.

Metagenomic profiling of gut microbiota in Fall Armyworm (Spodoptera frugiperda) larvae fed on different host plants.

BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda) is a polyphagous pest known for causing significant crop damage. The gut microbiota plays a pivotal role in influencing the biology, physiology and adaptation of the host. However, understanding of the taxonomic composition and functional characteristics of the gut microbiota in FAW larvae fed on different host plants remains limited. METHODS: This study utilized metagenomic sequencing to explore the structure, function and antibiotic resistance genes (ARGs) of the gut microbiota in FAW larvae transferred from an artificial diet to four distinct host plants: maize, sorghum, tomato and pepper. RESULTS: The results demonstrated significant variations in gut microbiota structure among FAW larvae fed on different host plants. Firmicutes emerged as the dominant phylum, with Enterococcaceae as the dominant family and Enterococcus as the prominent genus. Notably, Enterococcus casseliflavus was frequently observed in the gut microbiota of FAW larvae across host plants. Metabolism pathways, particularly those related to carbohydrate and amino acid metabolism, played a crucial role in the adaptation of the FAW gut microbiota to different host plants. KEGG orthologs associated with the regulation of the peptide/nickel transport system permease protein in sorghum-fed larvae and the 6-phospho-ß-glucosidase gene linked to glycolysis/gluconeogenesis as well as starch and sucrose metabolism in pepper-fed larvae were identified. Moreover, the study identified the top 20 ARGs in the gut microbiota of FAW larvae fed on different host plants, with the maize-fed group exhibiting the highest abundance of vanRC. CONCLUSIONS: Our metagenomic sequencing study reveals significant variations in the gut microbiota composition and function of FAW larvae across diverse host plants. These findings underscore the intricate co-evolutionary relationship between hosts and their gut microbiota, suggesting that host transfer profoundly influences the gut microbiota and, consequently, the adaptability and pest management strategies for FAW.