OrdinalCLIP: Learning Rank Prompts for Language-Guided Ordinal Regression

This paper presents a language-powered paradigm for ordinal regression. Existing methods usually treat each rank as a category and employ a set of weights to learn these concepts. These methods are easy to overfit and usually attain unsatisfactory performance as the learned concepts are mainly derived from the training set. Recent large pre-trained vision-language models like CLIP have shown impressive performance on various visual tasks. In this paper, we propose to learn the rank concepts from the rich semantic CLIP latent space. Specifically, we reformulate this task as an image-language matching problem with a contrastive objective, which regards labels as text and obtains a language prototype from a text encoder for each rank. While prompt engineering for CLIP is extremely time-consuming, we propose OrdinalCLIP, a differentiable prompting method for adapting CLIP for ordinal regression. OrdinalCLIP consists of learnable context tokens and learnable rank embeddings; The learnable rank embeddings are constructed by explicitly modeling numerical continuity, resulting in well-ordered, compact language prototypes in the CLIP space. Once learned, we can only save the language prototypes and discard the huge language model, resulting in zero additional computational overhead compared with the linear head counterpart. Experimental results show that our paradigm achieves competitive performance in general ordinal regression tasks, and gains improvements in few-shot and distribution shift settings for age estimation. The code is available at https://github.com/xk-huang/OrdinalCLIP.Comment: Accepted by NeurIPS2022. Code is available at https://github.com/xk-huang/OrdinalCLI

Mechanistic analysis of loess landslide reactivation in northern Shaanxi based on coupled numerical modeling of hydrological processes and stress strain evolution: A case study of the Erzhuangkelandslide in Yan’an

The Erzhuangke landslide is a typical landslide affected by the rainy season. Rainfall changes the seepage pattern with the pre-existing landslide, weakening matric suction and soil shear strength, leading to the formation of tension cracks internally. This triggers overall sliding and localized extensive deformations. Existing studies seldom considers the interaction between the seepage field and stress field of the Erzhuangke landslide. Therefore, based on the actual engineering geological disaster scenarios, supported by on-site monitoring data and terrain physical parameters, a geometric computational model is established, and hydraulic coupled numerical simulations are conducted. By investigating variations in saturation and pore pressure within the landslide, the paper explores the rainfall infiltration patterns. It examines the impact of rainfall intensity on landslide reactivation from the perspective of stress displacement. In addition, in order to validate the accuracy and feasibility of the method, selected measurement points from the landslide are matched with corresponding positions in the numerical model. Comparative analysis is performed on displacement, soil pressure, and saturation aspects, confirming that the numerical model effectively reflects the actual situation. Through coupling numerical simulations and the study of the reactivation mechanism of the old landslide under rainfall conditions, the paper interprets field data, analyzes the reactivation process, and provides theoretical foundations and technical guidance for subsequent engineering early warning and disaster mitigation works

Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells

<p>Abstract</p> <p>Background</p> <p>Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated.</p> <p>Results</p> <p>We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells.</p> <p>Conclusion</p> <p>These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.</p

Efficacy and safety of triazavirin therapy for coronavirus disease 2019 : A pilot randomized controlled trial

Acknowledgements: We are deeply grateful to the front-line clinicians who participated in the study while directly fighting the epidemic. This study was supported by the Chinese Academy of Engineering Projects for COVID-19 (2020-KYGG-01-04) and Heilongjiang Province Urgent Project-6 for COVID-19. Data and safety monitoring board members of this trial included Kang Li, Yong Zhang, Songjiang Liu, and Yaohui Shi.Peer reviewedPublisher PD

Recombinant proteins A29L, M1R, A35R, and B6R vaccination protects mice from mpox virus challenge

Since May 2022, mutant strains of mpox (formerly monkeypox) virus (MPXV) have been rapidly spreading among individuals who have not traveled to endemic areas in multiple locations, including Europe and the United States. Both intracellular and extracellular forms of mpox virus have multiple outer membrane proteins that can stimulate immune response. Here, we investigated the immunogenicity of MPXV structural proteins such as A29L, M1R, A35R, and B6R as a combination vaccine, and the protective effect against the 2022 mpox mutant strain was also evaluated in BALB/c mice. After mixed 15 μg QS-21 adjuvant, all four virus structural proteins were administered subcutaneously to mice. Antibody titers in mouse sera rose sharply after the initial boost, along with an increased capacity of immune cells to produce IFN-γ alongside an elevated level of cellular immunity mediated by Th1 cells. The vaccine-induced neutralizing antibodies significantly inhibited the replication of MPXV in mice and reduced the pathological damage of organs. This study demonstrates the feasibility of a multiple recombinant vaccine for MPXV variant strains

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine.

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants. In naïve animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccines targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection against Delta and Omicron BA.1variants. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by recall and reshape the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine-primed populations

Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

OBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS

Inhibition of profibrotic microRNA-21 affects platelets and their releasate.

Fibrosis is a major contributor to organ disease for which no specific therapy is available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how miR-21 inhibition may attenuate fibrosis using a proteomics approach. Transfection of miR-21 mimic or inhibitor in murine cardiac fibroblasts revealed limited effects on extracellular matrix (ECM) protein secretion. Similarly, miR-21-null mouse hearts showed an unaltered ECM composition. Thus, we searched for additional explanations as to how miR-21 might regulate fibrosis. In plasma samples from the community-based Bruneck Study, we found a marked correlation of miR-21 levels with several platelet-derived profibrotic factors, including TGF-β1. Pharmacological miR-21 inhibition with an antagomiR reduced the platelet release of TGF-β1 in mice. Mechanistically, Wiskott-Aldrich syndrome protein, a negative regulator of platelet TGF-β1 secretion, was identified as a direct target of miR-21. miR-21-null mice had lower platelet and leukocyte counts compared with littermate controls but higher megakaryocyte numbers in the bone marrow. Thus, to our knowledge this study reports a previously unrecognized effect of miR-21 inhibition on platelets. The effect of antagomiR-21 treatment on platelet TGF-β1 release, in particular, may contribute to the antifibrotic effects of miR-21 inhibitors

Apparent timing and duration of the Matuyama-Brunhes geomagnetic reversal in Chinese loess

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; The Matuyama-Brunhes (MB) geomagnetic reversal in Chinese loess has been studied extensively as an important boundary for land-ocean stratigraphic and paleoclimatic correlations. However, the apparent timing and duration of the MB boundary remain controversial in Chinese loess deposits due to its inconsistent stratigraphic position and the uncertain chronologies. Here we synthesized high-resolution paleomagnetic records from four loess sequences in the central Chinese Loess Plateau and synchronized the loess-paleosol chronology by matching the grain-size variations to orbitally tuned grain-size time series. The synthesized paleomagnetic results reveal consistent features of the MB transition in Chinese loess, including the stratigraphic position (L8/S8 transition), timing (&sim;808&ndash;826 ka), duration (&sim;14&ndash;16 ka), and rapid directional oscillations. Compared with the MB transition in marine records (770&ndash;775 ka), the timing of the MB transition is relatively older and longer in Chinese loess, due to a complex interplay between different remanence acquisition mechanisms which occurred during the course of postdepositional physical and chemical processes.</p