MTIE-Net: Multi-technology fusion of low-light image enhancement network.

Images obtained in low-light scenes are often accompanied by problems such as low visibility, blurred details, and color distortion, enhancing them can effectively improve the visual effect and provide favorable conditions for advanced visual tasks. In this study, we propose a Multi-Technology Fusion of Low-light Image Enhancement Network (MTIE-Net) that modularizes the enhancement task. MTIE-Net consists of a residual dense decomposition network (RDD-Net) based on Retinex theory, an encoder-decoder denoising network (EDD-Net), and a parallel mixed attention-based self-calibrated illumination enhancement network (PCE-Net). The low-light image is first decomposed by RDD-Net into a lighting map and reflectance map; EDD-Net is used to process noise in the reflectance map; Finally, the lighting map is fused with the denoised reflectance map as an input to PCE-Net, using the Fourier transform for illumination enhancement and detail recovery in the frequency domain. Numerous experimental results show that MTIE-Net outperforms the comparison methods in terms of image visual quality enhancement improvement, denoising, and detail recovery. The application in nighttime face detection also fully demonstrates its promise as a pre-processing means in practical applications.

BRD4-targeting PROTAC as a unique tool to study biomolecular condensates.

Biomolecular condensates play key roles in various biological processes. However, specific condensation modulators are currently lacking. PROTAC is a new technology that can use small molecules to degrade target proteins specifically. PROTAC molecules are expected to regulate biomolecular condensates dynamically by degrading/recovering key molecules in biomolecular condensates. In this study, we employed a BRD4-targeting PROTAC molecule to regulate the super-enhancer (SE) condensate and monitored the changes of SE condensate under PROTAC treatment using live-cell imaging and high-throughput sequencing technologies. As a result, we found that BRD4-targeting PROTACs can significantly reduce the BRD4 condensates, and we established a quantitative method for tracking BRD4 condensates by PROTAC and cellular imaging. Surprisingly and encouragingly, BRD4 condensates were observed to preferentially form and play specialized roles in biological process regulation for the first time. Additionally, BRD4 PROTAC makes it possible to observe the dynamics of other condensate components under the continued disruption of BRD4 condensates. Together, these results shed new light on research methods for liquid-liquid phase separation (LLPS), and specifically demonstrate that PROTAC presents a powerful and distinctive tool for the study of biomolecular condensates.

A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma.

Oral, gut, and tumor microbiota have been implicated as important regulators in the carcinogenesis and progression of gastrointestinal malignancies. However, few studies focused on the existence and association of resident microbes within different body regions. Herein, we aim to reveal the durability of the oral-gut-tumor microbiome and its diagnostic performance in hepatocellular carcinoma (HCC). Our study included two cohorts: a retrospective discovery cohort of 364 HBV-HCC patients and 160 controls with oral or fecal samples, a prospective validation cohort of 91 cases, and 124 controls for matching samples, as well as 48 HBV, and 39 HBV-cirrhosis patients for gut microbial patterns examined by 16S rRNA gene sequencing. With the random forest analysis, 10 oral and 9 gut genera that could distinguish HCC from controls in the retrospective cohort were validated among the prospective matching participants, with area under the curve (AUC) values of 0.7971 and 0.8084, respectively. When influential taxa were merged, the AUC of the consistent classifier increased to 0.9405. The performance continued to improve to 0.9811 when combined with serum levels of alpha-fetoprotein (AFP). Specifically, microbial biomarkers represented by Streptococcus displayed a constantly increasing trend during the disease transition. Furthermore, the presence of several dominant microbiota species was confirmed in hepatic tumor and non-tumor tissues with fluorescence in situ hybridization (FISH) and 5 R 16S rRNA gene sequencing. Overall, our findings based on the oral-gut-tumor microbiota provide a reliable approach for the early detection of HCC.

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin-proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article "PROTACs: great opportunities for academia and industry" in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020-2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.

Nonlinear interferometric surface-plasmon-resonance sensor.

A nonlinear interferometer can be constructed by replacing the beam splitter in the Mach-Zehnder interferometer with four-wave mixing (FWM) process. Meanwhile, the conventional surface plasmon resonance (SPR) sensors can be extensively used to infer the information of refractive index of the sample to be measured via either angle demodulation technique or intensity demodulation technique. Combined with a single FWM process, a quantum SPR sensor has been realized, whose noise floor is reduced below standard quantum limit with sensitivity unobtainable with classical SPR sensor. Therefore, in this work we have theoretically proposed a nonlinear interferometric SPR sensor, in which a conventional SPR sensor is placed inside nonlinear interferometer, which is called as I-type nonlinear interferometric SPR sensor. We demonstrate that near resonance angle I-type nonlinear interferometric SPR sensor has the following advantages: its degree of intensity-difference squeezing, estimation precision ratio, and signal-noise-ratio are improved by the factors of 4.6 dB, 2.3 dB, and 4.6 dB respectively than that obtained with a quantum SPR sensor based on a single FWM process. In addition, the theoretical principle of this work can also be expanded to other types of sensing, such as bending, pressure, and temperature sensors based on a nonlinear interferometer.

IL-1ß promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

Inflammatory factors play an important role in the process of fracture healing. The influence of interleukin (IL)-1ß, a key inflammatory factory, on new bone formation has been controversial. The aim of the present study was to investigate whether IL-1ß affects the osteogenic differentiation of mouse bone marrow mesenchymal stem cells (MBMMSCs), and examined its effective concentration range and molecular mechanism of action. MBMMSC proliferation in the presence of IL-1ß was observed using a Cell-Counting Kit-8 assay, and the effect of IL-1ß on MBMMSC apoptosis was examined via flow cytometry. Alkaline phosphatase assay, Alizarin Red staining and quantitative assays were performed to evaluate the osteogenic differentiation of MBMMSCs. The expression levels of osteogenic differentiation markers were detected using reverse transcription-quantitative PCR (RT-qPCR). It was demonstrated that within a concentration range of 0.01-1 ng/ml, IL-1ß promoted osteogenic differentiation of MBMMSCs and did not induce apoptosis. Furthermore, RT-qPCR results indicated that IL-1ß increased osteogenic gene expression within this concentration range. Moreover, Western blotting results identified that the bone morphogenetic protein/Smad (BMP/Smad) signaling pathway was significantly activated by IL-1ß under osteogenic conditions. Therefore, the present results suggested that within a certain concentration range, IL-1ß promoted osteogenic differentiation and function of MBMMSCs via the BMP/Smad signaling pathway.

Enhancement of quantum correlations using correlation injection scheme in a cascaded four-wave mixing processes.

Quantum correlations and entanglement shared among multiple quantum beams are important for both fundamental science and the development of quantum technologies. The enhancement for them is necessary and important to implement the specific quantum tasks and goals. Here, we report a correlation injection scheme (CIS) which is an effective method to enhance the quantum correlations and entanglement in the symmetrical cascaded four-wave mixing processes, and the properties of quantum correlations and entanglement can be characterized by the values of the degree of intensity-difference squeezing (DS) and the smallest symplectic eigenvalues, respectively. Our results show that the CIS can enhance the quantum correlations and entanglement under certain conditions, while for other conditions it can only decrease the values of the DS and the smallest symplectic eigenvalues to the level of standard quantum limit, respectively. We believe that our scheme is experimentally accessible and will contribute to a deeper understanding of the manipulations of the quantum correlations and entanglement in various quantum networks.

[Curative effect comparison for fixation of fibula or not for the treatment of middle and lower 1/3 fractures of tibia and fibula with intramedullary nail].

OBJECTIVE: To analyze and compare the effect of fibular plate fixation on the treatment of tibial and fibular fractures. METHODS: From July 2016 to September 2018, 65 cases of middle and lower 1/3 fractures of tibia and fibula were retrospectively analyzed, including 46 males and 19 females, aged 22 to 61 years old. There were 37 cases in fibular fixation group (27 males and 10 females) , 28 cases in fibular non fixation group (19 males and 9 females) . By comparing the operation time, intraoperative bleeding, fracture healing time, ankle rotation and valgus angle, postoperative complications, last follow-up ankle mobility and Baird Jackson score, the operation effect was evaluated. RESULTS: All patients were followed up for 12 to 16 months with an average of (13.67±1.23) months. There were 3 cases of infection of the fibular incision, all of which healed in the first stage without incision dehiscence, and 4 cases of delayed union without nonunion. In the fibula fixation group, the external rotation of ankle joint increased (7.16±1.36) ° and the valgus angle increased (3.35±1.16) °; while in the non fixation group, the external rotation increased (10.25±1.58) ° and the valgus angle increased (6.46±1.23) ° with statistical significance (P<0.05) . There was no significant difference in ankle joint activity, fracture healing time and complication rate between two groups (P>0.05) ; there was significant difference in operation time, intraoperative hemorrhage and Baird Jackson score at the latest follow-up (P<0.05) . CONCLUSION: The fibular plate fixation can prevent the ankle joint from malrotation and valgus deformity, and can obtain better surgical effect and functional prognosis.

Gram-scale total synthesis of teixobactin promoting binding mode study and discovery of more potent antibiotics.

Teixobactin represents a new class of antibiotics with novel structure and excellent activity against Gram-positive pathogens and Mycobacterium tuberculosis. Herein, we report a one-pot reaction to conveniently construct the key building block L-allo-Enduracidine in 30-gram scale in just one hour and a convergent strategy (3 + 2 + 6) to accomplish a gram-scale total synthesis of teixobactin. Several analogs are described, with 20 and 26 identified as the most efficacious analogs with 3~8-fold and 2~4-fold greater potency against vancomycin resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus respectively in comparison with teixobactin. In addition, they show high efficiency in Streptococcus pneumoniae septicemia mouse model and neutropenic mouse thigh infection model using methicillin-resistant Staphylococcus aureus. We also propose that the antiparallel ß-sheet of teixobactin is important for its bioactivity and an antiparallel dimer of teixobactin is the minimal binding unit for lipid II via key amino acids variations and molecular docking.

The Role of Polymorphisms in Genes of PI3K/Akt Signaling Pathway on Prostate.

Background and Objective: Increasing evidence suggested that polymorphisms in genes of PI3K/Akt pathway were closely related to prostate cancer (PCa) risk. Nevertheless, these results are controversial and inconclusive. Here, we conducted a comprehensive updated meta-analysis and systematic review to precisely illustrate the association between polymorphisms in genes of PI3K/Akt signaling pathway and PCa risk. Materials and Methods: The gene set of PI3K/Akt pathway was referenced from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website. Relevant studies were identified by the systematically researching on PubMed, Web of Science and Google Scholar databases up to October 1, 2017. The odds ratios (ORs) with a corresponding 95% confidential intervals (95%CIs) were applied to test their associations. All the analyses were conducted by using Stata 12.0 (Stata Corporation, USA). Results: Finally, 38 articles comprising 62 case-control studies were enrolled for 13 polymorphisms in genes of PI3K/Akt pathway. However, overall results failed to present a positive association between polymorphisms in genes of PI3K/Akt pathway and PCa risk. Nevertheless, in the subgroup analysis by ethnicity, we identified that IL-6-rs1800795 polymorphism was associated with an increased risk of PCa for Caucasian individuals in dominant model (MM + MW vs. WW: OR = 1.245, 95%CI = 1.176-1.318, P < 0.001). Conclusion: Our work suggests that polymorphisms in genes of PI3K/Akt Signaling Pathway are not risk factor for PCa. Further well-designed studies with larger samples and precise designs are demanded to corroborate our findings.

Hyperellipsoidal statistical classifications in a reproducing kernel Hilbert space.

Standard support vector machines (SVMs) have kernels based on the Euclidean distance. This brief extends standard SVMs to SVMs with kernels based on the Mahalanobis distance. The extended SVMs become a special case of the Euclidean distance when the covariance matrix in a reproducing kernel Hilbert space is degenerated to an identity. The Mahalanobis distance leads to hyperellipsoidal kernels and the Euclidean distance results in hyperspherical ones. In this brief, the Mahalanobis distance-based kernel in a reproducing kernel Hilbert space is developed systematically. Extensive experiments demonstrate that the hyperellipsoidal kernels slightly outperform the hyperspherical ones, with fewer SVs.