Supplementary Figure S3: Binding ability of Hu5F9/B2B, and their respective parent antibodies.

Supplementary Figure S12: In vivo PK profiles of TJH2201 in Balb/c mice.

Supplementary Figure S5: Microscopic images of in vitro RBC agglutination induced by Hu5F9/gp120 at concentrations from 0.046 µg/ml to 100 µg/ml. Scale bar = 100µm

Supplementary Figure S1: Hematological effects of Hu5F9 on hCD47 KI mice and hCD47/SIRPα DKI mice.

Supplementary Figure S4: Hematological effects of biparatopic CD47 antibody, Hu5F9/B2B, in vitro and in vivo.

Supplementary Figure S7: Epitope binning of indicated CD47 antibodies by biolayer interferometry.

Supplementary Figure S9: Microscopic images of in vitro RBC agglutination induced by TJH2201 at concentrations from 0.046 µg/ml to 100 µg/ml. Scale bar = 100 µm

The high mortality rate from hepatocellular carcinoma (HCC) is due primarily to challenges in early diagnosis and the development of drug resistance in advanced stages. Many first-line chemotherapeutic drugs induce ferroptosis, a form of programmed cell death dependent on ferrous iron-mediated oxidative stress, suggesting that drug resistance and ensuing tumor progression may in part stem from reduced ferroptosis. Since circular RNAs (circRNAs) have been shown to influence tumor development, we examined whether specific circRNAs may regulate drug-induced ferroptosis in HCC. Through circRNA sequencing, we identified a novel hsa_circ_0000195 (circTTC13) that is overexpressed in HCC tissues. This overexpression is linked to higher tumor grade, more advanced tumor stage, decreased ferroptosis, and poorer overall survival. Overexpression of CircTTC13 in HCC cell lines and explant tumors was associated with increased proliferation rates, enhanced metastatic capacity, and resistance to sorafenib, while also inhibiting ferroptosis. Conversely, circTTC13 silencing reduced malignant characteristics and promoted ferroptosis. In silico analysis, luciferase assays, and fluorescence in situ hybridization collectively demonstrated that circTTC13 directly targets and reduces miR-513a-5p expression, which in turn leads to the upregulation of the negative ferroptosis regulator SLC7A11. Moreover, the inhibition of SLC7A11 mirrored the effect of circTTC13 knockdown, whereas ferroptosis inhibition mimicked the effect of circTTC13 overexpression. Both circTTC13 and SLC7A11 were highly expressed in drug-resistant HCC cells, and circTTC13 silencing induced ferroptosis and reversed sorafenib resistance in explant tumors. These findings identify circTTC13 as a critical driver of HCC progression and resistance to drug-induced ferroptosis via upregulation of SLC7A11. The cicTTC13/miR-513a-5p/SLC7A11 axis represents a potential therapeutic target for HCC.

Table S3. The list of candidate genes

Table S4. The list of differentially expressed genes upon DDX6 or EDC4 knockout

Murals are an important part of human cultural heritage, reflecting the cultural characteristics of different periods and containing extremely high research value. However, for a long time, due to environmental factors such as humidity and temperature, as well as internal factors such as mural production materials and processes, mold has grown on murals, seriously affecting their aesthetics and preservation status. Mold disease labeling can detect mold growth and provide technical support for mold prevention and control. Traditional manual annotation methods are not only time-consuming and laborious, but also suffer from subjective errors and inconsistent annotation. Therefore, this article proposes a method for labeling fungal diseases in murals based on hyperspectral images, which can achieve automatic recognition and labeling of fungi on the surface of murals. This method first generates mold training samples based on hyperspectral image unmixing, and then proposes a mural mold labeling network framework based on a multi grouping strategy long short-term memory network and a multi-scale convolutional neural network (MGL-MC), effectively combining spatial and spectral information of mural hyperspectral images. The experiment shows that the method proposed in this article has a good effect on the recognition and labeling of mold on the surface of murals, and can improve the accuracy of mold detection.

Table S6. The list of differentially expressed proteins upon DDX6 or EDC4 knockout

Table S1. The list of oligos used in the study

Table S5. The list of peaks and genes enriched in DDX6-eCLIP-seq

BACKGROUND:Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of gastrointestinal bleeding. Mucosal apoptosis is an essential pathological feature of PHG. However, whether HIF-1α and p53 are involved in mucosal apoptosis and whether HIF-1α induces PHG by mediating p53 remains unclear.METHODS:Gastric mucosal injury and apoptosis were examined in PHG patients and animal models. The mechanisms of HIF-1α- and p53-mediated apoptosis were analyzed. The GES-1 cell line was used to elucidate the underlying mechanisms using siRNA knockdown of HIF-1α and p53 in a hypoxic environment in vitro.RESULTS:Epithelial apoptosis, HIF-1α, and p53 were markedly induced in the gastric mucosa of PHG. Apoptosis was attenuated in mice with HIF-1α- and p53-specific inhibitors. Apoptotic signaling factors were markedly induced in the gastric mucosa of PHG. Inhibition of p53 demonstrably attenuated the mucosal apoptosis; however, it did not affect HIF-1α expression. Conversely, targeted deletion of HIF-1α significantly inhibited p53 expression and attenuated the injury and p53-mediated apoptosis. Bax and Bcl-2 expression can be upregulated and downregulated by p53, respectively, to increasecleaved caspase-3 expression, which can be regulated by HIF-1α.CONCLUSIONS:These results indicate that HIF-1α regulates the p53-induced mucosal epithelial apoptotic signaling pathway and that HIF-1α and p53 are potential therapeutic targets for PHG.

In the investigation, protection and restoration of murals, the exact location and size of fragmentation disease can be labeled to facilitate the subsequent protection and cultural heritage of murals. However, manual labeling is time-consuming and laborious, and the results will be various due to the different experience of experts, which is not conducive to the promotion of intelligent cultural relic protection and restoration. The intelligent labeling of mural diseases through artificial intelligence can greatly improve the efficiency of mural restoration and solve these deficiencies. Therefore, an intelligent labeling method for mural fragments based on gradient-trainable Gabor and U-Net is proposed. In this paper, the disease labeling problem is transformed into the image segmentation problem for disease regions. However, due to the rich texture of the mural image and the complex edges of the fragmentation regions, a lot of detail is lost for disease labeling directly using the U-Net network. Different from previous studies, this method uses gradient-trained Gabor in the encoders to extract texture features of fragmentation disease and obtain more texture information of the disease region. In particular, res2convolution is embedded into the skip connections to narrow the semantic gap between encoder and decoder and better inject the texture information of fragmentation disease into the deep network. Finally, we proved that the method proposed in this paper can realize the intelligent labeling of fragmentation diseases accurately and efficiently through the murals of Han Tomb at Xi 'an Jiaotong University.

Background/Aims: Mathematical integration of all complications from the Clavien-Dindo classification into one number called the comprehensive complication index provides a novel method to capture morbidity. This objective of this study was to compare the evaluations of complications between the novel comprehensive complication index and Clavien-Dindo classification for portal hypertension patients who underwent splenectomy plus pericardial devascularization. Materials and Methods: Patients treated with either splenectomy plus simplified pericardial devascularization or splenectomy plus traditional pericardial devascularization were included retrospectively. Correlation and logistic regression analyses of the postoperative hospital stay and total hospitalization expense were compared between the comprehensive complication index and Clavien-Dindo classification. The cumulative sum-comprehensive complication index was generated and compared between operation types. Results: The Child-Pugh classification at admission, spleen thickness, and intraoperative blood loss were risk factors for high comprehensive complication index. Comprehensive complication index showed a stronger relationship with the postoperative hospital stay and total hospitalization expense than the Clavien-Dindo classification. Logistic regression analysis of the postoperative hospital stay demonstrated that the R-2 values for the comprehensive complication index and Clavien-Dindo classification were 0.15 and 0.14, respectively. The cumulative sum-comprehensive complication index graph showed a steady dynamic decrease in the cumulative sum score for the individual operation type, with splenectomy plus simplified pericardial devascularization revealing a more notable decrease than splenectomy plus traditional pericardial devascularization. Conclusions: Comprehensive complication index is an excellent method to assess postoperative morbidity in portal hypertension patients. The cumulative sum-comprehensive complication index chart can better dynamically monitor and compare different operation types. Splenectomy plus simplified pericardial devascularization is better than splenectomy plus traditional pericardial devascularization at decreasing cumulative sum-comprehensive complication index.

Backgrounds: Intrahepatic infiltration of neutrophils is a character of alcoholic acute-on-chronic liver failure (AACLF) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. Intestinal bacteria and the gut-liver axis have been thought to play a key role in many liver diseases also including AACLF. However, whether NETs appear in AACLF and play a role in AACLF is still unsure. Methods: WT, NE KO, and TLR4 KO mice were used to build the AACLF model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AACLF related markers were detected. Results: The serum MPO-DNA and LPS concentration was increased in AACLF patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AACLF mice by testing MPO-DNA, Cit H3, and NE. These markers decreased with gut detergent and restored markers with gut detergent plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AACLF related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with combined treatment with antibiotics plus LPS. But the liver injury, intrahepatic fat, fibro deposition, and liver inflammation-related markers did show a significant difference in TLR4 KO mice when they received the same treatment. Conclusion: Intestinal-derived LPS promotes NETs formation in AACLF through the TLR4 pathway and further accelerates the AACLF process by NETs.