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Wen-Shang Liu,1,* Yu Liu,2,* Jie Gao,3,* Hao Zheng,4 Zheng-Mao Lu,4 Meng Li1 1Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Li, Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China, Tel +086-15000879978, Fax +086-021-23271699, Email lemonlives_dr@163.com Zheng-Mao Lu, Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel +086-13651688596, Fax +086-021-31161589, Email luzhengmao1982@163.comAbstract: Wound healing is a complex and dynamic process, and metabolic disturbances in the microenvironment of chronic wounds and the severe symptoms they cause remain major challenges to be addressed. The inherent properties of hydrogels make them promising wound dressings. In addition, biomembrane-based nanostructures and microstructures (such as liposomes, exosomes, membrane-coated nanostructures, bacteria and algae) have significant advantages in the promotion of wound healing, including special biological activities, flexible drug loading and targeting. Therefore, biomembrane-based nanostructure- and microstructure-loaded hydrogels can compensate for their respective disadvantages and combine the advantages of both to significantly promote chronic wound healing. In this review, we outline the loading strategies, mechanisms of action and applications of different types of biomembrane-based nanostructure- and microstructure-loaded hydrogels in chronic wound healing.Keywords: biomembrane, nanostructures, microstructures, hydrogels, chronic wound healing

Immune checkpoint blockade (ICB) therapy has achieved remarkable benefits in the treatment of malignant tumors, but the clinical response rates are unsatisfied due to the low tumor immunogenicity and the abundant immunosuppressive cells. Herein, a plasma membrane targeted photodynamic nanoagonist (designated as PMTPN) is developed to potentiate ICB therapy by initiating tumor cell pyroptosis and depleting infiltrating B cells. PMTPN is composed of a rationally designed chimeric peptide sequence loaded with Bruton's tyrosine kinase inhibitor (Ibrutinib). Notably, PMTPN is capable of sequentially targeting tumor and tumor cell membrane to trigger immunogenic pyroptosis and cause overwhelming release of cytokines, promoting dendritic cells maturation, and cytotoxic T lymphocytes (CTLs) activation. Meanwhile, PMTPN can also deplete infiltrating B cells and reduce the secretion of interleukin-10 to decrease immunosuppressive regulatory T cells and enhance CTLs infiltration. Beneficially, the synergistic immune modulating characteristics of PMTPN potentiate ICB therapy to simultaneously eliminate primary and distant tumors. This study offers a promising strategy to elevate the immunotherapeutic response rate in consideration of the complex immunosuppressive factors., (© 2025 Wiley‐VCH GmbH.)

The process of wound healing is frequently impeded by metabolic imbalances within the wound microenvironment. MXenes exhibit exceptional biocompatibility, biodegradability, photothermal conversion efficiency, conductivity, and adaptable surface functionalization, demonstrating marked potential in the development of multifunctional platforms for wound healing. Moreover, the integration of MXenes with other bioactive nanomaterials has been shown to enhance their therapeutic efficacy, paving the way for innovative approaches to wound healing. In this review, we provide a systematic exposition of the mechanisms through which MXenes facilitate wound healing and offer a comprehensive analysis of the current research landscape on MXene-based multifunctional bioactive composites in this field. By delving into the latest scientific discoveries, we identify the existing challenges and potential future trajectories for the advancement of MXenes. Our comprehensive evaluation aims to provide insightful guidance for the formulation of more effective wound healing strategies., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2025 Dong Luo et al.)

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soy sauce aroma type Baijiu (SSAB) is a complex blend of seven rounds of raw SSAB, each with distinct aroma profiles that evolve during maturation. Tracking the aging of individual rounds is crucial for understanding flavor development. The round 1-4 SSABs were analyzed by gas chromatography-mass spectrometry and an electronic tongue over one-year aging. Results showed that short/medium-chain esters decrease while long-chain esters, acids, aldehydes, pyrazines, ketones, and furans increase. Kinetic analysis showed that short/medium-chain ethyl esters reach equilibrium in the esterification-hydrolysis reactions, whereas long-chain ethyl esters favor esterification, with their reaction quotient (Qc) diverging from the equilibrium point. Linoleic acid ethyl ester, identified as a key aging marker, was found to reduce the volatilization rate of critical aroma compounds in the finished glass, thereby prolonged the duration of lingering aromas. These findings provide a foundation for improving SSAB blending and storage, highlighting aging's key role in enhancing Baijiu quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors. Published by Elsevier Ltd.)

This paper introduces Re-DQN, a deep reinforcement learning-based algorithm for comprehensive coverage path planning in lawn mowing robots. In the fields of smart homes and agricultural automation, lawn mowing robots are rapidly gaining popularity to reduce the demand for manual labor. The algorithm introduces a new exploration mechanism, combined with an intrinsic reward function based on state novelty and a dynamic input structure, effectively enhancing the robot's adaptability and path optimization capabilities in dynamic environments. In particular, Re-DQN improves the stability of the training process through a dynamic incentive layer and achieves more comprehensive area coverage and shorter planning times in high-dimensional continuous state spaces. Simulation results show that Re-DQN outperforms the other algorithms in terms of performance, convergence speed, and stability, making it a robust solution for comprehensive coverage path planning. Future work will focus on testing and optimizing Re-DQN in more complex environments and exploring its application in multi-robot systems to enhance collaboration and communication.

1-Propanol is an important aroma compound in sauce-flavor Baijiu. However, the mechanism by which it affects the aroma of sauce-flavor Baijiu has not been fully investigated. In this study, an instrumental and perceptual analysis was employed to assess the impact of 1-propanol on the flavor and volatile compounds in sauce-flavor Baijiu. The combination of sensory evaluation and electronic tongue analysis revealed that 1-propanol diminished the floral and fruity flavor and increased the bitterness and astringency. According to SHS/GC-MS analysis, 1-propanol mainly inhibited the volatility of ethyl acetate, ethyl butyrate, ethyl valerate, and ethyl hexanoate. Further, the Feller additive model and odor activity value method confirmed the four binary mixtures formed by 1-propanol and four esters had masking effects. Finally, the partition coefficients were calculated to clarify the relationship between volatility and interaction of compounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Yeasts play a crucial role in determining the quality and yield of sauce-flavor Baijiu, yet the source, succession, and metabolic functions of the yeast community in fermented grains during stacking fermentation remains unclear. In this study, amplicon sequencing combined with solid-state fermentation was used to investigate the structure and function of yeast community during the first-round fermentation of sauce-flavor Baijiu. The richness and diversity of yeast community increased throughout fermentation, with 83.05 % of yeast ASV sourced from the fermentation environment. Fourteen yeast genera were identified, with Wickerhamomyces (29.6 %), Saccharomycopsis (25.0 %), and Torulaspora (14.9 %) being the predominant genera. These genera showed distinct spatial distributions throughout the fermentation stack. Spearman correlation analysis indicated positive correlations between the three genera and multiple volatiles in fermented grains alcohols and esters. After solid-state fermentation in pure culture, T. delbrueckii ME22, S. fibuligera ME8, and W. anomalus ME57 produced distinct floral, fruity, and sweet flavor compounds, such as phenylethyl alcohol, isoamyl alcohol, ethyl acetate, phenethyl acetate, and isoamyl acetate. T. delbrueckii ME22 demonstrated a great capacity for cellulose degradation, whereas S. fibuligera ME8 exhibited enhanced capabilities for protein and starch degradation. This study provides a theoretical reference for the application of yeast in the fermentation of sauce-flavor Baijiu., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Qu-aroma is of great significance for evaluation the quality of Daqu starter. This study aimed to decode the Qu-aroma of medium-temperature Daqu (MT-Daqu) via "top-down" and "bottom-up" approaches. Firstly, 52 aroma descriptors were defined to describe the MT-Daqu aroma by quantitative descriptive analysis. Secondly, 193 volatile organic compounds (VOCs) were identified from 42 MT-Daqu samples by HS-SPME-GC-MS, and 43 dominant VOCs were screened out by frequence of occurrence or abundance. By Thin Film (TF)-SPME-GC-O-MS, 27 odors and 90 VOCs were detected in MT-Daqu mixture, and 14 odor-active VOCs were screened out by odor intensity. Thirdly, a five-level MT-Daqu aroma wheel was constructed by matching 52 aroma descriptors and 37 aroma-active VOCs. Finally, Qu-aroma of MT-Daqu was reconstructed with 37 aroma-active VOCs and evaluated by omission experiments. Hereinto, 26 key aroma-active VOCs were determined by OAV value ≥1, including isovaleric acid, 1-hexanol, isovaleraldehyde, 2-octanone, trimethylpyrazine, γ-nonalactone, 4-vinylguaiacol, etc., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Genomic integration of heterologous genes is the preferred approach in industrial fermentation-related strains due to the drawbacks associated with plasmid-mediated microbial fermentation, including additional growth burden, genetic instability, and antibiotic contamination. Synthetic biology and genome editing advancements have made gene integration convenient. Integrated expression is extensively used in the field of biomanufacturing and is anticipated to become the prevailing method for expressing recombinant proteins. Therefore, it is pivotal to strengthen the expression of exogenous genes at the genome level. Here, we systematically optimized the integrated expression system of Escherichia coli from 3 aspects. First, the integration site slmA with the highest expression activity was screened out of 18 sites in the ORI region of the E. coli BL21 (DE3) genome. Second, we characterized 16 endogenous promoters in E. coli and combined them with the T7 promoter. A constitutive promoter, Plpp-T7, exhibited significantly higher expression strength than the T7 promoter, achieving a 3.3-fold increase in expression levels. Finally, to further enhance the T7 expression system, we proceeded with overexpression of T7 RNA polymerase at the chassis cell level. The resulting constitutive efficient integrated expression system (CEIES_Ecoli) showed a 2-fold increase in GFP expression compared to the pET3b recombinant plasmid. Therefore, CEIES_Ecoli was applied to the integrated expression of nitrilase and hyaluronidase, achieving stable and efficient enzyme expression, with enzyme activities of 22.87 and 12,195 U·mL -1 , respectively, comparable to plasmid levels. Overall, CEIES_Ecoli provides a stable and efficient method of gene expression without the need for antibiotics or inducers, making it a robust tool for synthetic biology, enzyme engineering, and related applications.

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Sarcopenia and cardiometabolic diseases have become important public health problems affecting the health and quality of life of the elderly. Reducing the incidence of sarcopenia is of positive significance for preventing and treating cardiometabolic diseases. This paper reviews the diagnostic criteria of sarcopenia in the elderly, the relationship between sarcopenia and cardiometabolic diseases, and the possible mechanisms. It provides support for the prevention and control of sarcopenia combined with cardiometabolic diseases.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ . Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

Long-chain fatty acids (LCFAs) are commonly presented in Baijiu, but their influence on flavor is ambiguous. The interaction between LCFAs and volatiles was systematically investigated in terms of chemometrics, sensory, and chemical-physical perceptions. The static-headspace-gas-chromatography-mass-spectrometry results demonstrated LCFAs suppressed the volatilizations of most volatiles. According to Phase-ratio-variation analysis, partition coefficients of ethyl acetate (EA) and ethyl hexanoate (EH) decreased 4%-31% and 27%-74%, while those of ethyl butyrate (EB) increased. Calculated by molecular dynamic simulation, the attractive intermolecular forces related to EA/EH increased with oleic acid (OA) addition, while those related to EB decreased. Sensory evaluation confirmed the olfactory threshold of EA and EH increased by 2.4 and 2.7 times respectively, but the threshold of EB decreased from 0.36 to 0.05 mg/L in the presence of OA. Overall, LCFAs altered the intermolecular interaction forces related to esters and ethanol, subsequently affecting the volatile profile and modifying Baijiu flavor's sensory perception., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Many traditional fermented foods and beverages industries around the world request the addition of multi-species starter cultures. However, the microbial community in starter cultures is subject to fluctuations due to their exposure to an open environment during fermentation. A rapid detection approach to identify the microbial composition of starter culture is essential to ensure the quality of the final products. Here, we applied single-cell Raman spectroscopy (SCRS) combined with machine learning to monitor Oceanobacillus species in Daqu starter, which plays crucial roles in the process of Chinese baijiu. First, a total of six Oceanobacillus species (O. caeni, O. kimchii, O. iheyensis, O. sojae, O. oncorhynchi subsp. Oncorhynchi and O. profundus) were detected in 44 Daqu samples by amplicon sequencing and isolated by pure culture. Then, we created a reference database of these Oceanobacillus strains which correlated their taxonomic data and single-cell Raman spectra (SCRS). Based on the SCRS dataset, five machine-learning algorithms were used to classify Oceanobacillus strains, among which support vector machine (SVM) showed the highest rate of accuracy. For validation of SVM-based model, we employed a synthetic microbial community composed of varying proportions of Oceanobacillus species and demonstrated a remarkable accuracy, with a mean error was less than 1% between the predicted result and the expected value. The relative abundance of six different Oceanobacillus species during Daqu fermentation was predicted within 60 min using this method, and the reliability of the method was proved by correlating the Raman spectrum with the amplicon sequencing profiles by partial least squares regression. Our study provides a rapid, non-destructive and label-free approach for rapid identification of Oceanobacillus species in Daqu starter culture, contributing to real-time monitoring of fermentation process and ensuring high-quality products., (© 2024 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)

For covert communication in lossy channels, it is necessary to consider that the carrier of the hidden watermark will undergo multiple image-processing attacks. In order to ensure that secret information can be extracted without distortion from the watermarked images that have undergone attacks, in this paper, we design a novel fragmented secure communication system. The sender will fragment the secret data to be transmitted and redundantly hide it in a large number of multimodal carriers of messenger accounts on multiple social platforms. The receiver receives enough covert carriers, extracts each fragment, and concatenates the transmitted secret data. This article uses the image carrier as an example to fragment the text file intended for transmission and embeds it into a large number of images, with each fragment being redundant and embedded into multiple images. In this way, at the receiving end, only enough stego images need to be received to extract the information in each image, and then concatenate the final secret file. In order to resist various possible attacks during image transmission, we propose a strong robust image watermarking method. This method adopts a watermark layer based on DFT, which has high embedding and detection efficiency and good invisibility. Secondly, a watermark layer based on DCT is adopted, which can resist translation attacks, JPEG attacks, and other common attacks. Experiments have shown that our watermarking method is very fast; both the embedding time and the extraction time are less than 0.15 s for images not larger than 2000×2000. Our watermarking method has very good invisibility with 41dB PSNR on average. And our watermarking method is more robust than existing schemes and robust to nearly all kinds of attacks. Based on this strong robust image watermarking method, the scheme of fragmenting and hiding redundant transmission content into a large number of images is effective and practical. Our scheme can 100% restore the secret file completely under different RST or hybrid attacks, such as rotation by 1 degree and 5 degrees, scaling by 1.25 and 0.8, and cropping by 10% and 25%. Our scheme can successfully restore the secret file completely even if 30% of received images are lost. When 80% of received images are lost, our scheme can still restore 61.1% of the secret file. If all stego images can be obtained, the original text file can be completely restored.

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o -bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

Single image dehazing is a challenging ill-posed problem which estimates latent haze-free images from observed hazy images. Some existing deep learning based methods are devoted to improving the model performance via increasing the depth or width of convolution. The learning ability of Convolutional Neural Network (CNN) structure is still under-explored. In this paper, a Detail-Enhanced Attention Block (DEAB) consisting of Detail-Enhanced Convolution (DEConv) and Content-Guided Attention (CGA) is proposed to boost the feature learning for improving the dehazing performance. Specifically, the DEConv contains difference convolutions which can integrate prior information to complement the vanilla one and enhance the representation capacity. Then by using the re-parameterization technique, DEConv is equivalently converted into a vanilla convolution to reduce parameters and computational cost. By assigning the unique Spatial Importance Map (SIM) to every channel, CGA can attend more useful information encoded in features. In addition, a CGA-based mixup fusion scheme is presented to effectively fuse the features and aid the gradient flow. By combining above mentioned components, we propose our Detail-Enhanced Attention Network (DEA-Net) for recovering high-quality haze-free images. Extensive experimental results demonstrate the effectiveness of our DEA-Net, outperforming the state-of-the-art (SOTA) methods by boosting the PSNR index over 41 dB with only 3.653 M parameters. (The source code of our DEA-Net is available at https://github.com/cecret3350/DEA-Net.).

Shiraia -like fungi, which are rare parasitic fungi found around bamboo, play an important role in traditional medicine. Their main active component, hypocrellin, is widely used in medicine, food, and cosmetics. By comparing strains with different hypocrellin yields, we identified a transcription factor ( SbTF ) in the hypocrellin biosynthesis pathway. SbTF from high-yielding zzz816 and low-yielding CNUCC C72 differed in its protein structure. Subsequently, SbTF from high-yielding zzz816 was overexpressed in several strains. This stabilised the yield in zzz816 and significantly increased the yield in low-yielding CNUCC C72. Comparing downstream non-essential genes between wild type and SbTF -overexpressing CNUCC C72 showed that SbMNF was significantly up-regulated. Therefore, it was selected for further study. SbMNF overexpression increased the hypocrellin yield in low-yielding CNUCC C72 and altered the composition of compounds in high-yielding CNUCC 1353PR and zzz816. This involved an increased elsinochrome C yield in CNUCC 1353PR and an increased hypocrellin B yield in zzz816 (by 2 and 70.3 times that in the corresponding wild type, respectively). This study is the first to alter hypocrellin synthesis to alter the levels of one bioactive agent compared to another. The results provide new insights regarding genetic modification and will help to optimise fungal fermentation., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To investigate the regulatory effect of interferon-α (IFN-α) on the apoptosis and killing function of CD56 dim CD57 + natural killer (NK) cells in systemic lupus erythematosus (SLE) patients, and to explore the specific mechanism., Methods: A total of sixty-four newly treated SLE patients and sixteen healthy controls (HC) enrolled in the Second Hospital of Dalian Medical University were selected as the research subjects. And the gene expression levels of molecules related to NK cell-killing function were detected by real-time quantitative polymerase chain reaction. CD56 dim CD57 + NK cells were co-cultured with the K562 cells, and the apoptotic K562 cells were labeled with Annexin-Ⅴ and 7-amino-actinomycin D. Peripheral blood mononuclear cells were treated with 20, 40, and 80 μmol/L hydrogen peroxide (H 2 O 2 ), and treated without H 2 O 2 as control, the expression level of perforin (PRF) was detected by flow cytometry. The concentration of IFN-α in serum was determined by enzyme linked immunosorbent assay. The expression levels of IFN-α receptors (IFNAR) on the surface of CD56 dim CD57 + NK cells were detected by flow cytometry, and were represented by mean fluorescence intensity (MFI). CD56 dim CD57 + NK cells were treated with 1 000 U/mL IFN-α for 24, 48 and 72 h, and no IFN-α treatment was used as the control, the apoptosis and the expression levels of mitochondrial reactive oxygen species (mtROS) were measured by flow cytometry and represented by MFI., Results: Compared with HC( n =3), the expression levels of PRF1 gene in peripheral blood NK cells of the SLE patients ( n =3) were decreased (1.24±0.41 vs . 0.57±0.12, P =0.05). Compared with HC( n =5), the ability of peripheral blood CD56 dim CD57 + NK cells in the SLE patients ( n =5) to kill K562 cells was significantly decreased (58.61%±10.60% vs . 36.74%±6.27%, P < 0.01). Compared with the control ( n =5, 97.51%±1.67%), different concentrations of H 2 O 2 treatment significantly down-regulated the PRF expression levels of CD56 dim CD57 + NK cells in a dose-dependent manner, the 20 μmol/L H 2 O 2 PRF was 83.23%±8.48% ( n =5, P < 0.05), the 40 μmol/L H 2 O 2 PRF was 79.53%±8.56% ( n =5, P < 0.01), the 80 μmol/L H 2 O 2 PRF was 76.67%±7.16% ( n =5, P < 0.01). Compared to HC ( n =16), the serum IFN-α levels were significantly increased in the SLE patients ( n =45) with moderate to high systemic lupus erythematosus disease activity index (SLEDAI≥10) [(55.07±50.36) ng/L vs . (328.2±276.3) ng/L, P < 0.001]. Meanwhile, compared with HC ( n =6), IFNAR1 expression in peripheral blood CD56 dim CD57 + NK cells of the SLE patients ( n =6) were increased (MFI: 292.7±91.9 vs . 483.2±160.3, P < 0.05), and compared with HC ( n =6), IFNAR2 expression in peripheral blood CD56 dim CD57 + NK cells of the SLE patients ( n =7) were increased (MFI: 643.5±113.7 vs . 919.0±246.9, P < 0.05). Compared with control ( n =6), the stimulation of IFN-α ( n =6) significantly promoted the apoptosis of CD56 dim CD57 + NK cells (20.48%±7.01% vs . 37.82%±5.84%, P < 0.05). In addition, compared with the control ( n =4, MFI: 1 049±174.5), stimulation of CD56 dim CD57 + NK cells with IFN-α at different times significantly promoted the production of mtROS in a time-dependent manner, 48 h MFI was 3 437±1 472 ( n =4, P < 0.05), 72 h MFI was 6 495±1 089 ( n =4, P < 0.000 1), but there was no significant difference at 24 h of stimulation., Conclusion: High serum IFN-α level in SLE patients may induce apoptosis by promoting mtROS production and inhibit perforin expression, which can down-regulate CD56 dim CD57 + NK killing function.

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated ZS111008 T , was isolated from high-temperature Daqu, a starter for production of Chinese Jiang-flavour Baijiu, and was characterized by polyphasic taxonomy. This novel isolate grew in the presence of 0-5 % (w/v) NaCl, at pH 6.0-9.0 and 25-45 °C; optimum growth was observed with 1 % (w/v) NaCl, at pH 8.0 and 30 °C. A comparative analysis of the 16S rRNA gene sequence (1461 bp) of strain ZS111008 T showed highest similarity to Solibacillus silvestris DSM12223 T (96.7%), followed by Solibacillus cecembensis PN5 T (96.6%) and Solibacillus isronensis AMCK01000046 (96.5%). The DNA G+C content of strain ZS111008 T was 37.21 mol%. The respiratory quinone was identified as menaquinone-7 and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unknown phospholipid. Lys was detected as the diagnostic diamino acid in the cell wall. Based on morphological characteristics, chemotaxonomic characteristics and physiological properties, strain ZS111008 T represents a novel species of the genus Solibacillus , for which the name Solibacillus daqui sp. nov. is proposed. The type strain for this proposed species is ZS111008 T (=CGMCC 1.19455 T =JCM 35214 T ).

Watermarking is an excellent solution to protect multimedia privacy but will be damaged by attacks such as noise adding, image filtering, compression, and especially scaling and cutting. In this paper, we propose a watermarking scheme to embed the watermark in the DWT-DCT composite transform coefficients, which is robust against normal image processing operations and geometric attacks. To make our scheme robust to scaling operations, a resampling detection network is trained to detect the scaling factor and then rescale the scaling-attacked image before watermark detection. To make our scheme robust to cutting operations, a template watermark is embedded in the Y channel to locate the cutting position. Experiments for various low- and high-resolution images reveal that our scheme has excellent performance in terms of imperceptibility and robustness.

Portable document format (PDF) files are widely used in file transmission, exchange, and circulation because of their platform independence, small size, good browsing quality, and the ability to place hyperlinks. However, their security issues are also more thorny. It is common to distribute printed PDF files to different groups and individuals after printing. However, most PDF watermarking algorithms currently cannot resist print-scan attacks, making it difficult to apply them in leak tracing of both paper and scanned versions of PDF documents. To tackle this issue, we propose an invisible digital watermarking technology based on modifying the edge pixels of text strokes to hide information in PDFs, which achieves high robustness to print-scan attacks. Moreover, it cannot be detected by human perception systems. This method focuses on the representation of text by embedding watermarks by changing the features of the text to ensure that changes in these features can be reflected in the scanned PDF after printing. We first segment each text line into two sub-blocks, then select the row of pixels with the most black pixels, and flip the edge pixels closest to this row. This method requires the participation of original PDF documents in detection. The experimental results show that all peak signal-to-noise ratio (PSNR) values of our proposed method exceed 32 dB, which indicates satisfactory invisibility. Meanwhile, this method can extract the hidden information with 100% accuracy under the JPEG compression attack, and has high robustness against noise attacks and print-scan attacks. In the case of no attacks, the watermark can be recovered without any loss. In terms of practical applications, our method can be applied in the practical leak tracing of official paper documents after distribution.

After being ingested and entering the human stomach, Helicobacter pylori ( H. pylori ) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

In order to more effectively monitor and interfere with enemy signals, it is particularly important to accurately and efficiently identify the intercepted signals and estimate their parameters in the increasingly complex electromagnetic environment. Therefore, in non-cooperative situations, it is of great practical significance to study how to accurately detect direct sequence spread spectrum (DSSS) signals in real time and estimate their parameters. The traditional time-delay correlation algorithm encounters the challenges such as peak energy leakage and false peak interference. As an alternative, this paper introduces a Pseudo-Noise (PN) code period estimation method utilizing a one-dimensional (1D) convolutional neural network based on the residual network (CNN-ResNet). This method transforms the problem of spread spectrum code period estimation into a multi-classification problem of spread spectrum code length estimation. Firstly, the In-phase/Quadrature(I/Q) two-way of the received DSSS signals is directly input into the CNN-ResNet model, which will automatically learn the characteristics of the DSSS signal with different PN code lengths and then estimate the PN code length. Simulation experiments are conducted using a data set with DSSS signals ranging from -20 to 10 dB in terms of signal-to-noise ratios (SNRs). Upon training and verifying the model using BPSK modulation, it is then put to the test with QPSK-modulated signals, and the estimation performance was analyzed through metrics such as loss function, accuracy rate, recall rate, and confusion matrix. The results demonstrate that the 1D CNN-ResNet proposed in this paper is capable of effectively estimating the PN code period of the non-cooperative DSSS signal, exhibiting robust generalization abilities.

Tumors are among the leading causes of death worldwide. Cell-derived biomimetic functional materials have shown great promise in the treatment of tumors. These materials are derived from cell membranes, extracellular vesicles and bacterial outer membrane vesicles and may evade immune recognition, improve drug targeting and activate antitumor immunity. However, their use is limited owing to their low drug-loading capacity and complex preparation methods. Liposomes are artificial bionic membranes that have high drug-loading capacity and can be prepared and modified easily. Although they can overcome the disadvantages of cell-derived biomimetic functional materials, they lack natural active targeting ability. Lipids can be hybridized with cell membranes, extracellular vesicles or bacterial outer membrane vesicles to form lipid-hybrid cell-derived biomimetic functional materials. These materials negate the disadvantages of both liposomes and cell-derived components and represent a promising delivery platform in the treatment of tumors. This review focuses on the design strategies, applications and mechanisms of action of lipid-hybrid cell-derived biomimetic functional materials and summarizes the prospects of their further development and the challenges associated with it., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 is reported to be involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis., Methods: We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro., Results: The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro., Conclusions: LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis, which may contribute to the development of novel potential clinical therapy for sepsis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated ZS110521 T , was isolated from high-temperature Daqu , a starter for production of Chinese Jiang-flavour Baijiu and was characterised by polyphasic taxonomy. This novel isolate grew in the presence of 0-20 % (w/v) NaCl, at pH 6.0-9.0 and 20-50 °C; optimum growth was observed with 8-10 % (w/v) NaCl, at pH 7.0 and 37 °C. A comparative analysis of the 16S rRNA gene sequence (1460 bp) of ZS110521 T revealed that it displayed the highest similarity to Lentibacillus populi WD4L-1 T (95.5 %), followed by Lentibacillus garicola SL-MJ1 T (95.4 %) and Lentibacillus lacisalsi BH260 T (95.2 %). ANI and dDDH values between ZS110521 T and other strains of species of the genus Lentibacillus were less than 78 and 28 %, respectively. The predominant cellular fatty acids (> 10 %) of ZS110521 T were anteiso-C 17 : 0 (37.8 %), anteiso-C 15 : 0 (28.1 %) and iso-C 16 : 0 (15.5 %). The respiratory quinone was identified as menaquinone-7 (MK-7) and the major polar lipids were diphosphatidylglycerol and phosphatidylglycerol. The polyphasic taxonomic data and the results of chemotaxonomic analysis confirmed that ZS110521 T represents a novel species, for which the name Lentibacillus daqui sp. nov. is proposed. The type strain of this proposed species is ZS110521 T (=CGMCC 1.19456 T =JCM 35213 T ).

With the wide application of direct sequence spread spectrum (DSSS) signals, the comprehensive performance of DSSS communication systems has been continuously improved, making the electronic reconnaissance link in communication countermeasures more difficult. Electronic reconnaissance technology, as the fundamental means of modern electronic warfare, mainly includes signal detection, recognition, and parameter estimation. At present, research on DSSS detection algorithms is mostly based on the correlation characteristics of DSSS signals, and autocorrelation algorithm is the most mature and widely used method in practical engineering. With the continuous development of deep learning, deep-learning-based methods have gradually been introduced to replace traditional algorithms in the field of signal processing. This paper proposes a spread spectrum signal detection method based on convolutional neural network (CNN). Through experimental analysis, the detection performance of the CNN model proposed in this paper on DSSS signals in various situations has been compared and analyzed with traditional autocorrelation detection methods for different signal-to-noise ratios. The experiments verified the estimation performance of the model in this paper under different signal-to-noise ratios, different spreading code lengths, different spreading code types, and different modulation methods and compared it with the autocorrelation detection algorithm. It was found that the detection performance of the model in this paper was higher than that of the autocorrelation detection method, and the overall performance was improved by 4 dB.

Nitrilase can catalyze nitrile compounds to generate corresponding carboxylic acids. Nitrilases as promiscuous enzymes can catalyze a variety of nitrile substrates, such as aliphatic nitriles, aromatic nitriles, etc. However, researchers tend to prefer enzymes with high substrate specificity and high catalytic efficiency. In this study, we developed an active pocket remodeling (ALF-scanning) based on modulating the geometry of the nitrilase active pocket to alter substrate preference and improve catalytic efficiency. Using this strategy, combined with site-directed saturation mutagenesis, we successfully obtained 4 mutants with strong aromatic nitrile preference and high catalytic activity, W170G, V198L, M197F, and F202M, respectively. To explore the synergistic relationship of these 4 mutations, we constructed 6 double-combination mutants and 4 triple-combination mutants. By combining mutations, we obtained the synergistically enhanced mutant V198L/W170G, which has a significant preference for aromatic nitrile substrates. Compared with the wild type, its specific activities for 4 aromatic nitrile substrates are increased to 11.10-, 12.10-, 26.25-, and 2.55-fold, respectively. By mechanistic dissection, we found that V198L/W170G introduced a stronger substrate-residue π-alkyl interaction in the active pocket and obtained a larger substrate cavity (225.66 Å 3 to 307.58 Å 3 ), making aromatic nitrile substrates more accessible to be catalyzed by the active center. Finally, we conducted experiments to rationally design the substrate preference of 3 other nitrilases based on the substrate preference mechanism and also obtained the corresponding aromatic nitrile substrate preference mutants of these three nitrilases and these mutants with greatly improved catalytic efficiency. Notably, the substrate range of SmNit is widened. IMPORTANCE In this study, the active pocket was largely remodeled based on the ALF-scanning strategy we developed. It is believed that ALF-scanning not only could be employed for substrate preference modification but might also play a role in protein engineering of other enzymatic properties, such as substrate region selectivity and substrate spectrum. In addition, the mechanism of aromatic nitrile substrate adaptation we found is widely applicable to other nitrilases in nature. To a large extent, it could provide a theoretical basis for the rational design of other industrial enzymes., Competing Interests: The authors declare no conflict of interest.

The underlying mechanisms of Cinnamomum kanehirae -stimulated growth and metabolism of Antrodia camphorata remain unknown. Herein, we first observed that the methanol extract of C. kanehirae trunk (MECK) (2 g/L) showed a potent stimulatory effect on A. camphorata triterpenoids production (115.6 mg/L). Second, MECK treatment considerably increased the category and abundance of many secondary metabolites in the mycelia. We identified 93 terpenoids (8 newly formed and 49 upregulated) in the MECK-treated mycelia, wherein 21 terpenoids were the same as those in the fruiting bodies. Third, 42 out of the 93 terpenoids were annotated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, mainly involving monoterpenoids and diterpenoids syntheses. Finally, 27 monoterpenes and 16 sesquiterpenes were detected in the MECK, and the two terpenoids with the highest abundance (linalool and α-pinene) were selected for verification and found to considerably increase the terpenoids production of A. camphorata and demonstrate the regulation of mRNA expression levels of nine key genes in the mevalonate pathway via RT-qPCR. This study is beneficial for elucidating the terpenoids synthesis mechanism in A. camphorata .

The aged Chinese liquor, Baijiu, is highly valued for its superior organoleptic qualities. However, since age-authentication method and aging-mechanism elucidation of Baijiu is still in the exploratory stage, high-quality aged Baijiu is often replaced by lower-quality, less-aged product with fraudulent mislabeling. Authentic high-quality strong-flavor Baijiu was analyzed by gas chromatography-mass spectrometry. Total esters decreased with aging, while acids, alcohols, aldehydes, ketones, terpenes, pyrazines increased. Although concentrations of partial compounds showed non-monotonic profiling during aging, a close positive linear correlation (R 2  = 0.7012) of Baijiu Evenness index (0.55-0.59) with aging time was observed, indicating a more balanced composition in aged Baijiu. The reaction quotient (Qc) of each esterification, calculated by the corresponding reactant and product concentration, approached to the corresponding thermodynamic equilibrium constant Kc. This result demonstrated that the spontaneous transformation driven by thermodynamics explained part of the aging compositional profiling. Furthermore, an aging-related feature selection and an age-authentication method were established based on three models combined with five ranking algorithms. Forty-one key features, including thirty-six compound concentrations, four esterification Qc values and the Evenness index were selected out. The age-authentication based on neural network using forty-one input features accurately predicted the age group of Baijiu samples (F1 = 100 %). These findings have deepened understanding of the Baijiu aging mechanism and provided a novel, effective approach for age-authentication of Baijiu and other liquors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

As the saccharifying and fermentative agent, medium-temperature Daqu (MT-Daqu) plays an irreplaceable role in the production of strong-flavor Baijiu. Numerous studies have focused on the microbial community structure and potential functional microorganisms, however, little is known about the succession of active microbial community and the formation mechanism of community function during MT-Daqu fermentation. In this study, we presented an integrated analysis of metagenomics, metatranscriptomics, and metabonomics covering the whole fermentation process of MT-Daqu to reveal the active microorganisms and their participations in metabolic networks. The results showed that dynamic of metabolites were time-specific, and the metabolites and co-expressed active unigenes were further classified into four clusters according to their accumulation patterns, with members within each cluster displaying a uniform and clear pattern of abundance across fermentation. Based on KEGG enrichment analysis in co-expression clusters and succession of active microbial community, we revealed that Limosilactobacillus, Staphylococcus, Pichia, Rhizopus, and Lichtheimia were metabolically active members at the early stage, and their metabolic activities were conducive to releasing abundant energy to drive multiple basal metabolisms such as carbohydrates and amino acids. Thereafter, during the high temperature period and at the end of fermentation, multiple heat-resistant filamentous fungi were transcriptionally active populations, and they acted as both the saccharifying agents and flavor compound producers, especially aromatic compounds, suggesting their crucial contribution to enzymatic activity and aroma of mature MT-Daqu. Our findings revealed the succession and metabolic functions of the active microbial community, providing a deeper understanding of their contribution to MT-Daqu ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Broad bean paste-meju was fermented by a mixture of broad bean koji and saline; koji fermentation is an essential process for the production of broad bean paste-meju. Aspergillus oryzae was the most widely used in sauce fermentation. The purpose of this study was to research the factory adaptability of the highly efficient A. oryzae PNM003 and further evaluate the effect of fermentation conditions and fermentation strains on koji. A. oryzae PNM003 was compared with the widely used strain HN 3.042 not only in the laboratory but also in factory conditions (large scale). Results showed that the koji made with the same starter in the factory had a greater amount of fungi than that in the laboratory. Bacteria and yeast levels in HN&#95;L koji were higher than in PN&#95;L koji. As for fungi constitution, almost only Aspergillus survived in the end through the microorganism self-purification process during koji fermentation. As for the bacterial constitution, koji was grouped by fermentation conditions instead of fermentation starter. PN koji had higher protease activity and a higher content of total acids, amino acid nitrogen, amino acids, and organic acids in the laboratory conditions. Nevertheless, in factory conditions, PN koji and HN koji had similar indexes. As for volatile flavor compounds, koji made with the two starters in the same condition was grouped together. As for the same starter, there were more flavor compounds metabolized in the factory condition than in the laboratory condition, especially esters and alcohols. The results showed PN was a highly efficient strain to ferment koji, but the advantages were expressed more remarkably in laboratory conditions. In brief, the fermented condition had a greater influence than the fermentation starter for broad bean koji., Competing Interests: HL, W-QD, Q-SZ, and GC were employed by Sichuan Food Fermentation Industry Research and Design Institute Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Lu, Deng, Zhang, Chen, Li, Xu and Ma.)

Introduction: This study compared differences in physicochemical characteristics of the vinegar made by a mixed culture (MC) of Saccharomyces cerevisiae and Lactiplantibacillus plantarum and a pure culture (PC) of Saccharomyces cerevisiae ., Methods: The fermentation process was monitored, and metabolomics analysis by Liquid Chromagraphy-Mass Spectrometry (LC-MS) was applied to the compositional differences between PC and MC vinegars, combined with quantification of organic acids, amino acids and B vitamins., Results: A total of 71 differential metabolites including amino acids, organic acids and carbohydrates, and six possible key metabolic pathways were identified. MC enhanced the malic acid utilization and pyruvate acid metabolism during fermentation, increasing substrate-level phosphorylation, and supplying more energy for cellular metabolism. Higher acidity at the beginning of acetic acid fermentation, resulting from lactic acid production by Lactiplantibacillus plantarum in MC, suppressed the cellular metabolism and growth of Acetobacter pasteurianus , but enhanced its alcohol metabolism and acetic acid production in MC. MC vinegar contained more vitamin B, total flavonoids, total organic acids, amino acids and had a higher antioxidant capacity. MC enhanced the volatile substances, particularly ethyl lactate, ethyl caprate and ethyl caproate, which contributed to a stronger fruity aroma., Discussion: These results indicated the mixed culture in alcoholic fermentation can effectively enhance the flavor and quality of apple cider vinegar., Competing Interests: Y-LD was employed by Lvjie Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Luo, Lu, Dong, Chai, Shi, Zhang and Xu.)

The intestines play a crucial role in the development of sepsis. The balance between autophagy and apoptosis in intestinal epithelial cells is dynamic and determines intestinal permeability. The present study focused on the potential role of autophagy in sepsis-induced intestinal barrier dysfunction and explored the mechanisms in vivo and in vitro. Excessive apoptosis in intestinal epithelia and a disrupted intestinal barrier were observed in septic mice. Promoting autophagy with rapamycin reduced intestinal epithelial apoptosis and restored intestinal barrier function, presenting as decreased serum diamine oxidase (DAO) and fluorescein isothiocyanate-dextran 40 (FD40) levels and increased expression of zonula occludens-1 (ZO-1) and Occludin. Polo-like kinase 1 (PLK1) knockdown in mice ameliorated intestinal epithelial apoptosis and the intestinal barrier during sepsis, whereas these effects were reduced with chloroquine and enhanced with rapamycin. PLK1 also promoted cell autophagy and improved lipopolysaccharide-induced apoptosis and high permeability in vitro. Moreover, PLK1 physically interacted with mammalian target of rapamycin (mTOR) and participated in reciprocal regulatory crosstalk in intestinal epithelial cells during sepsis. This study provides novel insight into the role of autophagy in sepsis-induced intestinal barrier dysfunction and indicates that the PLK1-mTOR axis may be a promising therapeutic target for sepsis., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile., (© 2022. The Author(s).)

Wolfram syndrome is a rare genetic spectrum disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, accompanied by other variable clinical manifestations. At present, the prognosis of this syndrome is very poor, the specific molecular mechanism is not clear, effective treatments are lacking to delay, prevent or reverse the development of Wolfram syndrome, and many patients die prematurely due to severe neurological dysfunction. This increases the urgency of the research on the pathogenic molecular mechanism related to Wolfram syndrome and the development of new therapies. This article summarizes the research progress on the pathogenic molecular mechanism and treatment status of Wolfram syndrome, in order to provide reference for the further mechanism research, prevention and treatment of Wolfram syndrome.

Objective: Obesity and overweight are risk factors for chronic disease worldwide. The purpose of this study was to compare the transcriptome of exercise-induced fat mobilization in obese people, and to explore the effect of different exercise intensity on the correlation of immune microenvironment remodeling and lipolysis in adipose tissue., Materials and Methods: Microarray datasets of adipose tissue before and after exercise were downloaded from the Gene Expression Omnibus. Then, we used gene-enrichment analysis and PPI-network construction to elucidate the function and enrichment pathways of the differentially expressed genes (DEGs) and to identify the central genes. A network of protein-protein interactions was obtained using STRING and visualized with Cytoscape., Results: A total of 929 DEGs were identified between 40 pre-exercise (BX) samples and 65 post-exercise (AX) samples from GSE58559, GSE116801, and GSE43471. Among these DEGs, adipose tissue-expressed genes were duly recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were mostly enriched in lipid metabolism. Studies have found that mitogen-activated protein kinase (MAPK) signaling pathway and forkhead box O (FOXO) signaling pathway are up-regulated, while Ribosome, coronavirus disease (COVID-19) and IGF-1 gene are down-regulated. Although we found the up-regulated genes that noted IL-1 among others, and the down-regulated gene was IL-34. The increase of inflammatory factors leads to changes in cellular immune microenvironment, and high-intensity exercise leads to increased expression of inflammatory factors in adipose tissue, leading to inflammatory responses., Conclusions: Exercise at different intensities leads to the degradation of adipose and is accompanied by changes in the immune microenvironment within adipose tissue. High intensity exercise can cause the imbalance of immune microenvironment of adipose tissue while causing fat degradation. Therefore, moderate intensity and below exercise is the best way for the general population to reduce fat and weight.

The purpose of image dehazing is to remove the interference from weather factors in degraded images and enhance the clarity and color saturation of images to maximize the restoration of useful features. Single image dehazing is one of the most important tasks in the field of image restoration. In recent years, due to the progress of deep learning, single image dehazing has made great progress. With the success of Transformer in advanced computer vision tasks, some research studies also began to apply Transformer to image dehazing tasks and obtained surprising results. However, both the deconvolution-neural-network-based dehazing algorithm and Transformer based dehazing algorithm magnify their advantages and disadvantages separately. Therefore, this paper proposes a novel Transformer-Convolution fusion dehazing network (TCFDN), which uses Transformer's global modeling ability and convolutional neural network's local modeling ability to improve the dehazing ability. In the Transformer-Convolution fusion dehazing network, the classic self-encoder structure is used. This paper proposes a Transformer-Convolution hybrid layer, which uses an adaptive fusion strategy to make full use of the Swin-Transformer and convolutional neural network to extract and reconstruct image features. On the basis of previous research, this layer further improves the ability of the network to remove haze. A series of contrast experiments and ablation experiments not only proved that the Transformer-Convolution fusion dehazing network proposed in this paper exceeded the more advanced dehazing algorithm, but also provided solid and powerful evidence for the basic theory on which it depends.