FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux.

Rationale: Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. Methods: We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. Results: DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. Conclusions: In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.

16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. METHODS: DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient's foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot. RESULTS: Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3+, CD4+, and low CD8+ levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8+, and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1ß, LDH, IL-18, GSDMD, NLRP3, and caspase-3). CONCLUSION: Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

OBJECTIVE: To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. METHODS: Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. RESULTS: Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. CONCLUSION: Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.

Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient suffering from infertility concomitant with OAT. Whole-exome sequencing (WES) confirmed the presence of a homozygous variant (NM_003462: c.464-1G > A) in the DNALI1 gene via Sanger sequencing. Immunofluorescence staining demonstrated that the DNALI1 signal was nearly undetectable in the patient's sperm. Bioinformatics analysis revealed that this mutation could reverse the splicing of the exon 4 acceptor splice site. A minigene experiment was performed to verify the mutation and the results confirmed that the mutation disrupted the splicing. Our findings show that this rare mutation in DNALI1 contributes to male infertility and OAT in humans, thereby expanding our understanding of the causes and pathogenesis of male infertility. This knowledge facilitates genetic counseling, clinical diagnosis, and therapeutic development of male infertility.

Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIM: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes. MATERIALS AND METHODS: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24. RESULTS: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%). CONCLUSIONS: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders.

Verifying AXL and putative proteins as SARS-CoV-2 receptors by DnaE intein-based rapid cell-cell fusion assay.

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.

DeepSG2PPI: A Protein-Protein Interaction Prediction Method Based on Deep Learning.

Protein-protein interaction (PPI) plays an important role in almost all life activities. Many protein interaction sites have been confirmed by biological experiments, but these PPI site identification methods are time-consuming and expensive. In this study, a deep learning-based PPI prediction method, named DeepSG2PPI, is developed. First, the protein sequence information is retrieved and the local context information of each amino acid residue is calculated. A two-dimensional convolutional neural network (2D-CNN) model is employed to extract features from a two-channel coding structure, in which an attention mechanism is embedded to assign higher weights to key features. Second, the global statistical information of each amino acid residue and the relationship graph between the protein and GO (Gene Ontology) function annotation are built, and the graph embedding vector is constructed to represent the biological features of the protein. Finally, a 2D-CNN model and two 1D-CNN models are combined for PPI prediction. The comparison analysis with existing algorithms shows that the DeepSG2PPI method has better performance. It provides more accurate and effective PPI site prediction, which will be helpful in reducing the cost and failure rate of biological experiments.

Inhibition of CEBPB Attenuates Lupus Nephritis via Regulating Pim-1 Signaling.

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to inflammatory damage in multiple target organs, and lupus nephritis (LN) is one of the most life-threatening organ manifestations. CCAAT/enhancer-binding protein ß (CEBPB) regulates the NLRP3 inflammasome and is involved in the pathogenesis of SLE. However, the role and mechanism of CEBPB in LN remains unclear. MRL/lpr mice and lipopolysaccharides (LPS) combined with adenosine triphosphate- (ATP-) treated glomerular podocytes were used as models of LN in vivo and in vitro, respectively. In vivo, we investigated the expressions of CEBPB during the development of MRL/lpr mice. Then we assessed the effect of CEBPB inhibition on renal structure and function through injecting shCEBPB lentivirus into MRL/lpr mice. In vitro, glomerular podocytes were treated with Pim-1-OE and siCEBPB to explore the relation between CEBPB and Pim-1. The progression of LN in mice was associated with the increased level of CEBPB, and the inhibition of CEBPB ameliorated renal structure impairments and improved renal function damage associated with LN. Knockdown of CEBPB could suppress the activation of NLRP3 inflammasome and the secretion of IL-1ß and IL-6. Furthermore, the knockdown of CEBPB could inhibit NLRP3 inflammasome activation and pyroptosis via binding to Pim-1 promoter to downregulate its expression, and the overexpression of Pim-1 reversed the effects of CEBPB deficiency. The regulation of CEBPB on Pim-1 facilitated pyroptosis by activating NLRP3 inflammasome, thereby promoting the development of LN.

Correlation between Insulin Resistance and Microalbuminuria Creatinine Ratio in Postmenopausal Women.

Objective: To study the relationship between insulin resistance and urinary microalbumin creatinine ratio in postmenopausal women. Methods: The selected research group comprised 104 postmenopausal women with type 2 diabetes who were admitted to the Department of Endocrinology in the green card center at the First Affiliated Hospital of Hainan Medical University between 2017 and 2019 inclusive. Ninety-eight postmenopausal women with the normal blood glucose metabolism hospitalized in the same period were used as the control group. The age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, fasting blood glucose, fasting insulin (FINS), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and urinary albumin-creatinine ratio (UACR) were analyzed. The insulin resistance index (HOMR-IR) was calculated, and the correlation between IR and UACR was analyzed. Results: Levels of HOMA-IR, SBP, HbA1c, HDL-C, LDL-C, TC, TG, FPG, FINS, and UACR in the study group were higher than those in the control group, and a significant difference was found between the groups (P < 0.05). The level of DBP in the study group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Pearson correlation analysis showed that UACR was positively correlated with HOMA-IR and HbA1c (r = 0.254, r = 0.565, P < 0.01). Multiple linear stepwise regression analysis further showed that HOMA-IR and age were positively correlated with UACR (P < 0.05). Conclusion: There is a correlation between IR and UACR in postmenopausal women. IR is an independent risk factor for UACR.

PregGAN: A prognosis prediction model for breast cancer based on conditional generative adversarial networks.

BACKGROUND AND OBJECTIVE: Generative adversarial network (GAN) is able to learn from a set of training data and generate new data with the same characteristics as the training data. Based on the characteristics of GAN, this paper developed its capability as a tool of disease prognosis prediction, and proposed a prognostic model PregGAN based on conditional generative adversarial network (CGAN). METHODS: The idea of PregGAN is to generate the prognosis prediction results based on the clinical data of patients. PregGAN added the clinical data as conditions to the training process. Conditions were used as the input to the generator along with noises. The generator synthesized new samples using the noises vectors and the conditions. In order to solve the mode collapse problem during PregGAN training, Wasserstein distance and gradient penalty strategy were used to make the training process more stable. RESULTS: In the prognosis prediction experiments using the METABRIC breast cancer dataset, PregGAN achieved good results, with the average accurate (ACC) of 90.6% and the average AUC (area under curve) of 0.946. CONCLUSIONS: Experimental results show that PregGAN is a reliable prognosis predictive model for breast cancer. Due to the strong ability of probability distribution learning, PregGAN can also be used for the prognosis prediction of other diseases.

Effect of Sperm 26S Proteasome on Embryo Formation and Development in In Vitro Fertilization.

The aim of this study was to evaluate the effects of sperm proteasome activity on fertilization outcome and embryo development after IVF. Following density gradient centrifugation for IVF purpose, the spermatozoa of 84 infertile patients with tubal factor were evaluated by luciferase enzymatic activity to assess the proteasome quantity. The mean age of patients was 33.8 years, and the mean concentration of human spermatozoa 26S proteasome was 674.53 ng/ml. After IVF, the embryos were scored for morphology. The spermatozoa proteasome activity was both positively correlated with fertilization rate in vitro (P = 0.0003) and 2PN rate (P = 0.0007). Compared to low fertilization rate group, the high fertilization rate group showed a significantly higher level of spermatozoa proteasome activity (P = 0.002). In conclusion, sperm proteasome activity provides additional data on sperm functional capacity in terms of fertilization during IVF.

Single-cell transcriptome analysis uncovers the molecular and cellular characteristics of thin endometrium.

Infertility is a social and medical problem around the world and the incidence continues to rise. Thin endometrium (TE) is a great challenge of infertility treatment, even by in vitro fertilization and embryo transfer. It is widely believed that TE impairs endometrium receptivity. However, only a few studies have explained the molecular mechanism. Herein, in order to reveal the possible mechanism, we sampled endometrium from a TE patient and a control volunteer and got a transcriptomic atlas of 18 775 individual cells which was constructed using single-cell RNA sequencing, and seven cell types have been identified. The cells were acquired during proliferative and secretory phases, respectively. The proportion of epithelial cells and stromal cells showed a significant difference between the TE group and the control group. In addition, differential expressed genes (DEGs) in diverse cell types were revealed, the enriched pathways of DEGs were found closely related to the protein synthesis in TE of both proliferative and secretory phases. Some DEGs can influence cell-type ratio and impaired endometrial receptivity in TE. Furthermore, divergent expression of estrogen receptors 1 and progesterone receptors in stromal and epithelial cells were compared in the TE sample from the control. The cellular and molecular heterogeneity found in this study provided valuable information for disclosing the mechanisms of impaired receptivity in TE.

Identification and characterization of novel compound heterozygous variants in FSHR causing primary ovarian insufficiency with resistant ovary syndrome.

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI.

The protective effects of S14G-humanin (HNG) against streptozotocin (STZ)-induced cardiac dysfunction.

Excessive oxidative stress, inflammation, and myocardial hypertrophy have been associated with diabetic cardiomyopathy (DCM). S14G-humanin (HNG) is a potent humanin analogue that has demonstrated cytoprotective effects in a variety of cells and tissues. However, the pharmacological function of HNG in diabetic cardiomyopathy has not yet been reported. In the present study, we investigated the protective effects of HNG against streptozotocin (STZ)-induced cardiac dysfunction in diabetic mice. Myocardial hypertrophy in diabetic mice was determined using Wheat Gem Agglutinin (WGA) staining. The heart function was measured with Echocardiographic imaging. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) proteins in plasma were measured using enzyme-linked immunosorbent assay (ELISA) kits. Protein expression of Phosphorylated p38/p38 was determined using western blots. We found that HNG treatment attenuated the STZ-induced myocardial hypertrophy and significantly improved heart function. Also, its treatment proved effective as it reduced the levels of several myocardial injury indicators, including creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and both the cardiac and plasma levels of TNF-α and IL-6, highlighting its effect on the STZ-induced myocardial injury. Lastly, HNG suppressed the activation of the p38/nuclear factor kappa-B (NF-κB) signaling pathway. S14G humanin possesses protective effects against streptozotocin-induced cardiac dysfunction through inhibiting the activation of the p38/NF-κB signaling pathway.

Iron overload compromises preimplantation mouse embryo development.

We and others have previously shown that abnormal pelvic environment plays an important role in the unexplained infertility of endometriosis. However, whether iron overload caused by ectopic periodic bleeding found in patients with endometriosis participates in endometriosis-associated reproductive failure is unknown. This study aimed to investigate effects of iron at level relevant to pelvic iron overload on the development of preimplantation mouse embryo. Two-cell embryos were collected, and cultured to blastocysts in G1/G2 medium supplemented with iron alone or in combination with iron chelator. The development rates, ATP level, mitochondrial membrane potential (MMP), reactive oxygen species level (ROS), and apoptotic and ferroptotic indices were compared between control and iron treatments across each specific developmental stage. Prolonged exposure to iron remarkably impaired early embryo development in vitro by hampering blastocyst formation (P < 0.001), which could be partly restored by iron chelator (P < 0.001). The arrest of embryo development was linked with iron-initiated mitochondrial dysfunction with reduction of ATP generation and MMP (P < 0.05 and P < 0.001, respectively). Impaired mitochondria altered ROS accumulation post-iron exposure at morula stage and blastocyst stage (P < 0.05). Moreover, Iron-exposed blastocyst stage embryos showed higher apoptotic and ferroptotic rates (P < 0.001 and P < 0.05, respectively). Our results highlight that pathologically relevant level of iron compromises preimplantation mouse embryo development by disrupting mitochondrial function and triggering both apoptosis and ferroptosis, which implicates that excess iron found in peritoneal fluid of women with endometriosis likely participates in endometriosis-associated reproductive failure.

Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance.

Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent ß-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

Clinical Characteristics and Prognosis of Renal Thrombotic Microangiopathy in Lupus Nephritis.

INTRODUCTION: LN is an important complication affecting the prognosis of SLE. We retrospectively analysed the influence of thrombotic microangiopathy (TMA) on LN, identified risk factors of TMA in LN and renal failure in LN-TMA, and evaluated the availability of plasmapheresis. METHODS: After balancing epidemiological characteristics and pathological types between groups, 127 patients (LN-TMA:42, LN:85) were included. After consulting medical records and followup data, we used the corresponding statistical methods, such as chi-squared test and Student's t-test, to compare differences in various aspects and explore the correlation among factors. RESULTS: LN-TMA patients had significantly higher blood urea nitrogen (13.2 mmol/L vs. 7.5 mmol/L, P < .001), systolic and diastolic blood pressures (both P < .01), serum creatinine (157.75 µmol/L vs. 79.00 µmol/L, P < .001), lactic dehydrogenase (P < .05), renal activity index (8.00 vs. 2.00; P < .001), SLE disease activity index score (13.8 ± 3.4 vs. 10.88 ± 6.0; P < .01), and pleurisy (P < .01) and lower haemoglobin (84.4 ± 20.14 vs. 99.38 ± 23.45 g/L, P < .05), platelets (87 vs. 155 ×109/L, P < .001), estimated glomerular filtration rate (39.24 vs. 97.40 mL/min/ 1.73m2, P < .05), and 3- and 5-year renal survival rates (P < .001 and P < .01, respectively) than non- TMA patients. Infection and TMA (P < 0.01) were independent risk factors for LN-TMA and renal failure, respectively. There was no obvious effect of plasmapheresis. CONCLUSION: TMA is an independent risk factor for renal failure in LN. As TMA affects the severity and prognosis of LN, identifying specific diagnostic indicators and effective treatment for LN is necessary.

Palladium(II)-catalyzed aerobic oxidative O-H/C-H isocyanide insertion: facile access to pyrrolo[2,1-c][1,4]benzoxazine derivatives.

Palladium-catalyzed aerobic oxidative cyclizations of substituted 2-(1H-pyrrol-1-yl)phenols with isocyanides via an O-H/C-H insertion cascade have been developed. This strategy provides facile access to pyrrolo[2,1-c][1,4]benzoxazine derivatives in good to excellent yields under an O2 atmosphere. The notable features of this protocol include its mild reaction conditions, atom-economy, and broad functional group tolerance.

Islet-cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfß signaling in mice.

Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet-cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild-type mice, Ica69-deficient mice have more severe liver injury, delayed liver regeneration, and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgfß-induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.

Application and interpretation of deep learning methods for the geographical origin identification of Radix Glycyrrhizae using hyperspectral imaging.

Radix Glycyrrhizae is used as a functional food and traditional medicine. The geographical origin of Radix Glycyrrhizae is a determinant factor influencing the chemical and physical properties as well as its medicinal and health effects. The visible/near-infrared (Vis/NIR) (376-1044 nm) and near-infrared (NIR) hyperspectral imaging (915-1699 nm) were used to identify the geographical origin of Radix Glycyrrhizae. Convolutional neural network (CNN) and recurrent neural network (RNN) models in deep learning methods were built using extracted spectra, with logistic regression (LR) and support vector machine (SVM) models as comparisons. For both spectral ranges, the deep learning methods, LR and SVM all exhibited good results. The classification accuracy was over 90% for the calibration, validation, and prediction sets by the LR, CNN, and RNN models. Slight differences in classification performances existed between the two spectral ranges. Further, interpretation of the CNN model was conducted to identify the important wavelengths, and the wavelengths with high contribution rates that affected the discriminant analysis were consistent with the spectral differences. Thus, the overall results illustrate that hyperspectral imaging with deep learning methods can be used to identify the geographical origin of Radix Glycyrrhizae, which provides a new basis for related research.