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Diabetic nephropathy (DN) is a prevalent microvascular complication that occurs often in individuals with diabetes. It significantly raises the mortality rate of affected patients. Therefore, there is an urgent need to identify therapeutic targets for controlling and preventing the occurrence and development of DN. Bile acids (BAs) are now recognized as intricate metabolic integrators and signaling molecules. The activation of BAs has great promise as a therapeutic approach for preventing DN, renal damage caused by obesity, and nephrosclerosis. The nuclear receptors (NRs), farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR); and the G protein-coupled BA receptor, Takeda G-protein-coupled receptor 5 (TGR5) have important functions in controlling lipid, glucose, and energy metabolism, inflammation, as well as drug metabolism and detoxification. Over the past 10 years, there has been advancement in comprehending the biology and processes of BA receptors in the kidney, as well as in the creation of targeted BA receptor agonists. In this review, we discuss the role of BA receptors, FXR, PXR, VDR, and TGR5 in DN and their role in renal physiology, as well as the development and application of agonists that activate BA receptors for the treatment of kidney diseases., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

The pattern of itching in patients with atopic dermatitis has not been systematically studied. Therefore, this study aimed to assess the pattern of itching in adults with atopic dermatitis using questionnaires to assess for a circadian rhythm of itching in participating patients at a single institution (n = 241). A self-report questionnaire was used to assess circadian rhythm and intensity of itching in patients. In addition, the patients' disease severity (Eczema Area and Severity Index [EASI]) and quality of life (Dermatology Life Quality Index [DLQI]) were assessed. Itching occurred most frequently (74.69%) and with the greatest severity (62.66%) between 20:00 and 00:00, and the least number of patients (25.31%) experienced itching between 04:00 and 08:00. The DLQI and EASI scores both correlated with the average and maximum itch intensity (r = 0.582, r = 0.533, respectively; r = 0.539, r = 0.517, respectively; p < 0.001). The DLQI and EASI scores were associated with average itch intensity (B = 0.179, B = 0.204, respectively; 95% CI: 0.112 to 0.246, 95% CI: 0.096 to 0.313, respectively; p < 0.001), and the EASI score was associated with males and family history (B = 0.285, B = 0.287, respectively; 95% CI: 0.094 to 0.476, 95% CI: 0.096 to 0.478, respectively; p = 0.003). Adult patients with atopic dermatitis exhibited a circadian rhythm of itching; these study results could positively impact treatment approaches.

Grain weight, grain number per panicle, and the number of panicles are the three factors that determine rice (Oryza sativa L.) yield. Of these, grain weight, which not only directly determines rice yield but also influences appearance and quality, is often considered the most important for rice production. Here, we describe OsNF-YC1, a member of the NF-Y transcription factor family that regulates rice grain size. OsNF-YC1 knockout plants (osnf-yc1), obtained using CRISPR-Cas9 technology, showed reduced grain weight due to reduced width and thickness, with no change in grain length, leading to a slenderer grain shape. Downregulation of OsNF-YC1 using RNA interference resulted in similar grain phenotypes as osnf-yc1. OsNF-YC1 affects grain formation by regulating both cell proliferation and cell expansion. OsNF-YC1 localizes in both the nucleus and cytoplasm, has transcriptional activation activity at both the N-terminus and C-terminus, and is highly expressed in young panicles. OsNF-YC1 interacts with OsMADS1 both in vivo and in vitro. Further analysis showed that the histone-like structural CBFD-NFYB-HMF domain of OsNF-YC1 conserved in the OsNF-YC transcription factor family can directly interact with the MADS-box domain of OsMADS1 to enhance its transcriptional activation activity. This interaction positively regulates the expression of OsMADS55, the direct downstream target of OsMADS1. Therefore, this paper reveals a potential grain size regulation pathway controlled by an OsNF-YC1-OsMADS1-OsMADS55 module in rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: The role of conversion surgery in patients with unresectable biliary tract cancer who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery., Methods: In this cohort study, patients with advanced biliary tract cancer who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed., Results: Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months postinitiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (nonsurgical group). The median interval from the initial antitumor therapy to surgery was 6.7 [interquartile range (IQR) 4.9-9.2] months. Survival with conversion surgery was significantly longer than the nonsurgical cohort, with a median progression-free survival (PFS) [unreached vs. 12.4 months; hazard ratio 0.17 (95% CI: 0.06-0.48); P =0.001] and overall survival (OS) [unreached vs. 22.4 months; hazard ratio 0.28 (95% CI: 0.09-0.84); P =0.02], respectively. After a median postoperative follow-up of 32.2 months in the surgical cohort, eight patients survived without recurrence. The estimated 3-year OS, PFS, and recurrence-free survival rate in the surgical cohort were 59.9, 59.2, and 60.6%, respectively. The R0 resection rate reached 92.3%, with two achieving a pathological complete response. One patient experienced a Clavien-Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS ( P =0.03) and PFS survival ( P =0.003)., Conclusion: Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The farnesoid X receptor (FXR), a ligand-activated transcription factor, plays a crucial role in regulating bile acid metabolism within the enterohepatic circulation. Beyond its involvement in metabolic disorders and immune imbalances affecting various tissues, FXR is implicated in microbiota modulation, gut-to-brain communication, and liver disease. The liver, as a pivotal metabolic and detoxification organ, is susceptible to damage from factors such as alcohol, viruses, drugs, and high-fat diets. Chronic or recurrent liver injury can culminate in liver fibrosis, which, if left untreated, may progress to cirrhosis and even liver cancer, posing significant health risks. However, therapeutic options for liver fibrosis remain limited in terms of FDA-approved drugs. Recent insights into the structure of FXR, coupled with animal and clinical investigations, have shed light on its potential pharmacological role in hepatic fibrosis. Progress has been achieved in both fundamental research and clinical applications. This review critically examines recent advancements in FXR research, highlighting challenges and potential mechanisms underlying its role in liver fibrosis treatment.

Cotton is one of the world's most important economic crops. Verticillium wilt is a devastating cotton disease caused by Verticillium dahliae , significantly impacting cotton yield and quality. E3 ubiquitin ligases are essential components of the ubiquitin-mediated 26S proteasome system, responsible for recognizing ubiquitinated target proteins and promoting their degradation, which play a crucial regulatory role in plant immune responses. In this study, on the basis of the confirmation of differential expression of GhDIRP1 , a RING-type E3 ubiquitin ligase encoding gene, in two cotton varieties resistant (Zhongzhimian 2) or susceptible (Jimian 11) to V. dahliae , we demonstrated that GhDIRP1 is a negative regulator of V. dahliae resistance because silencing GhDIRP1 in cotton and heterogeneously overexpressing the gene in Arabidopsis enhanced and compromised resistance to V. dahliae , respectively. The GhDIRP1 -mediated immune response seemed to be realized through multiple physiological pathways, including hormone signaling, reactive oxygen species, and lignin biosynthesis. Based on the sequences of GhDIRP1 isolated from Zhongzhimian 2 and Jimian 11, we found that GhDIRP1 had identical coding but different promoter sequences in the two varieties, with the promoter of Zhongzhimian 2 being more active than that of Jimian 11 because the former drove a stronger expression of GUS and LUC reporter genes. The results link the ubiquitination pathway to multiple physiological pathways acting in the cotton immune response and provide a candidate gene for breeding cotton varieties resistant to V. dahliae .

Type 2 innate lymphoid cells were found to be members of the innate immune cell family, which is involved in innate and adaptive immunity to resist the invasion of foreign antigens and induce allergic reactions caused by allergens. The advancement of ILC2 research has pointed out that ILC2s have a high degree of diversity, challenging the notion of their homogeneity as a cellular population. An increasing number of studies indicate that ILC2 is a cell population with tissue specificity which can be induced by the tissue microenvironment. In addition, crosstalk between tissues can change ILC2 functions of migration and activation. Here, we emphasize that ILC2 undergoes adaptive changes under the regulation of the tissue microenvironment and distant tissues, thereby coordinating the organization's operation. In addition, ILC2 alterations induced by the tissue microenvironment are not limited to the ILC2 cell population, and ILC2 can also transdifferentiate into another class of ILC cell population (ILC1 or ILC3). In this review, we summarized the tissue-specific effects of ILC2 by tissue microenvironment and focused on the function of ILC2 in inter-tissue crosstalk. Lastly, we discussed the transdifferentiations of ILC2 caused by the abnormal change in tissue environment., (© 2024. The Author(s).)

Three-dimensional (3D) light field displays can provide an immersive visual perception and have attracted widespread attention, especially in 3D light field communications, where 3D light field displays can provide face-to-face communication experiences. However, due to limitations in 3D reconstruction and dense views rendering efficiency, generating high-quality 3D light field content in real-time remains a challenge. Traditional 3D light field capturing and reconstruction methods suffer from high reconstruction complexity and low rendering efficiency. Here, a Real-time optical flow representation for the high-resolution light field is proposed. Based on the principle of 3D light field display, we use optical flow to ray trace and multiplex sparse view pixels. We simultaneously synthesize 3D light field images during the real-time interpolation process of views. In addition, we built a complete capturing-display system to verify the effectiveness of our method. The experiments' results show that the proposed method can synthesize 8 K 3D light field videos containing 100 views in real-time. The PSNR of the virtual views is around 32 dB and SSIM is over 0.99, and the rendered frame rate is 32 fps. Qualitative experimental results show that this method can be used for high-resolution 3D light field communication.

The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure., (© 2024. The Author(s).)

The sea cucumber is an essential nutrient source and a significant economic marine resource associated with successful aquaculture. However, sea cucumbers are highly susceptible to autolysis induced by endogenous protease after postmortem, and the phenomenon of body wall "melting" occurs, which seriously affects the food quality of products and the degree of acceptance by consumers. To satisfy the growing demand for fresh or processed sea cucumbers, we must clarify the autolysis mechanism of sea cucumbers and the methods to achieve autolysis regulation. In this paper, the factors leading to the quality deterioration and texture softening of sea cucumbers are reviewed, with emphasis on enzymatic characteristics, the autolysis mechanism, the effects of autolysis on the physicochemical properties of the body wall of the sea cucumber, and the development of potential natural protease inhibitors. We aim to provide some reference in future preservation and processing processes for sea cucumbers, promote new processing and preservation technologies, and advance the sea cucumber industry's development.

Three-dimensional (3D) light-field display technology can reconstruct the spatial characteristics of 3D scenes and provide users with an immersive visual experience without the need for any additional external devices. Here, an arbitrary stylized light-field generation method for 3D light-field displays is presented, and the tripartite constraints are addressed by conducting style transformation in a refined feature space. A multi-dimensional feature refinement module is designed to learn which aspects and regions should be prioritized within the high-level feature grid of the scene, which allows content and style patterns to be better matched and blended. To preserve more structural details and reduce artifacts, a novel global quality and local structure joint loss function is used for optimization. A mask-guided light-field coding method based on ray-casting is employed to accelerate the synthesis of stylized light-field images. Experimental results demonstrate that the proposed method can generate higher-quality stylized 3D light-field content with any given style in a zero-shot manner. Additionally, the method provides two user control extensions to further enrich the ways for the personalized editing of 3D content displayed on 3D light-field displays.

Holographic displays are ideal display technologies for virtual and augmented reality because all visual cues are provided. However, real-time high-quality holographic displays are difficult to achieve because the generation of high-quality computer-generated hologram (CGH) is inefficient in existing algorithms. Here, complex-valued convolutional neural network (CCNN) is proposed for phase-only CGH generation. The CCNN-CGH architecture is effective with a simple network structure based on the character design of complex amplitude. A holographic display prototype is set up for optical reconstruction. Experiments verify that state-of-the-art performance is achieved in terms of quality and generation speed in existing end-to-end neural holography methods using the ideal wave propagation model. The generation speed is three times faster than HoloNet and one-sixth faster than Holo-encoder, and the Peak Signal to Noise Ratio (PSNR) is increased by 3 dB and 9 dB, respectively. Real-time high-quality CGHs are generated in 1920 × 1072 and 3840 × 2160 resolutions for dynamic holographic displays.

We aimed to explore the anti-obesity mechanism from the microbiome, metabolome, and transcriptome viewpoints, focusing on the sulfated polysaccharides found in the cooking liquid of Apostichopus japonicus (CLSP AJ ) to explore the potential mediators of the anti-obesity effects in mice fed a high-fat diet (HFD). The mice treated with CLSP AJ showed a decrease in obesity and blood lipid levels. Gut microbiome dysbiosis caused by the HFD was reversed after CLSP AJ supplementation, along with increased levels of indole-3-ethanol, N-2-succinyl-L-glutamic acid 5-semialdehyde, and urocanic acid. These increases were positively related to the increased Akkermansia , Lactobacillus , Roseburia , and Phascolarctobacterium . Transcriptome analysis showed that B cell receptor signaling and cytochrome P450 xenobiotic metabolism were the main contributors to the improvement in obesity. Metabolome-transcriptome analysis revealed that CLSP AJ reversal of obesity was mainly due to amino acid metabolism. These findings suggest that CLSP AJ could be a valuable prebiotic preparation for preventing obesity-related diseases., Competing Interests: The authors declare no conflict of interest.

Background: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy- ε -pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound., Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry., Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype., Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Zhang et al.)

Trypanosoma brucei, a causative agent of human and animal trypanosomiasis, regularly switches its major surface antigen to avoid elimination by the immune system. Toll-like receptor 9 (TLR9) is a key modulator for resistance to host-infective trypanosomes; however, the underlying molecular mechanism remains indistinct. Thus, we first approached the issue using Tlr9-mutant mice that render them non-responsive to TLR9 agonists. After infection, T cells in the spleens of Tlr9-mutant mice were analyzed by flow cytometry and a reduction in CD8 + , CD4 + T, and NKT cells was observed in Tlr9-mutant mice compared to WT mice. We further found that the responses of inflammatory cytokines in the sera were reduced in Tlr9-mutant mice after T. brucei infection. The underlying molecular mechanism was that T. b. brucei DNA activated TLR9, which consequently upregulated the expression of p38 and ERK/MAPK, resulting in host resistance to trypanosome infection. In conclusion, these findings provide novel insights into the TLR9-mediated host responses to trypanosome infection., 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 B.V. All rights reserved.)

To explore the combination effects of plasma-activated water and dielectric barrier discharge (PAW-DBD) cold plasma treatment on the formation of volatile flavor and lipid oxidation in Asian sea bass (ASB), the volatile flavor compounds and lipid profiles were characterized by gas chromatography-ion mobility spectrometry and LC-MS-based lipidomics analyses. In total, 38 volatile flavor compound types were identified, and the PAW-DBD group showed the most kinds of volatile components with a significant (p < 0.05) higher content in aldehydes, ketones, and alcohols. A total of 1500 lipids was detected in lipidomics analysis, phosphatidylcholine was the most followed by triglyceride. The total saturated fatty acids content in PAW-DBD group increased by 105.02 μg/g, while the total content of unsaturated fatty acids decreased by 275.36 μg/g. It can be concluded that the PAW-DBD processing increased both the types and amounts of the volatile flavor in ASB and promoted lipid oxidation by altering lipid profiles., 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.)

Interdiffusion and solid-solid phase reaction at the interface between thermoelectric (TE) materials and the electrode critically influence interfacial transport properties and the overall energy conversion efficiency during service. Here, the microstructural evolution and diffusion mechanisms at the interfaces between the most widely used Bi 2 Te 3 -based TE materials, n-type Bi 2 Te 2.7 Se 0.3 (BTS) and p-type Bi 0.5 Sb 1.5 Te 3 (BST), and Ni electrodes were investigated at atomic resolution using spherical aberration-corrected scanning transmission electron microscopy (STEM). The BTS(0001)/Ni and BST(0001)/Ni interfaces were constructed by depositing Ni nanoparticles on mechanically exfoliated BTS and BST bulk materials and subsequent annealing. The interfacial reaction is initially dominated by Ni diffusion into the TE matrix to form NiAs-type NiM intermetallics, while Ni trans-quintuple-layer diffusion only occurs in Sb-rich BST. The Bi-rich BTS is more influenced by the Ni-Te preferential reaction, resulting in NiM abnormal grain growth and the formation of tilted and rotated interfaces. Bi diffusion into the BTS matrix forms a Bi double layer at the interface or Bi 2 [Bi 2 (Te,Se) 3 ] as the annealing temperature increases, while Bi diffusion into the Ni thin film greatly accelerates the interfacial reaction rate, as elucidated by in situ heating STEM. The results provide essential structural details to understand and prevent the degradation of TE device performance.

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection., (© 2024. The Author(s).)

Background: The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood., Methods: From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC., Results: Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6-8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria ( Actinomyces&#95;sp&#95;ICM47 , and Senegalimassilia&#95;anaerobia ) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI., Conclusions: In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: White matter injury (WMI) represents a significant etiological factor contributing to neurological impairment subsequent to Traumatic Brain Injury (TBI). CD36 receptors are recognized as pivotal participants in the pathogenesis of neurological disorders, including stroke and spinal cord injury. Furthermore, dynamic fluctuations in the phenotypic polarization of microglial cells have been intimately associated with the regenerative processes within the injured tissue following TBI. Nevertheless, there is a paucity of research addressing the impact of CD36 receptors on WMI and microglial polarization. This investigation aims to elucidate the functional role and mechanistic underpinnings of CD36 in modulating microglial polarization and WMI following TBI., Methods: TBI models were induced in murine subjects via controlled cortical impact (CCI). The spatiotemporal patterns of CD36 expression were examined through quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescence staining. The extent of white matter injury was assessed via transmission electron microscopy, Luxol Fast Blue (LFB) staining, and immunofluorescence staining. Transcriptome sequencing was employed to dissect the molecular mechanisms underlying CD36 down-regulation and its influence on white matter damage. Microglial polarization status was ascertained using qPCR, Western blot analysis, and immunofluorescence staining. In vitro, a Transwell co-culture system was employed to investigate the impact of CD36-dependent microglial polarization on oligodendrocytes subjected to oxygen-glucose deprivation (OGD)., Results: Western blot and qPCR analyses revealed that CD36 expression reached its zenith at 7 days post-TBI and remained sustained at this level thereafter. Immunofluorescence staining exhibited robust CD36 expression in astrocytes and microglia following TBI. Genetic deletion of CD36 ameliorated TBI-induced white matter injury, as evidenced by a reduced SMI-32/MBP ratio and G-ratio. Transcriptome sequencing unveiled differentially expressed genes enriched in processes linked to microglial activation, regulation of neuroinflammation, and the TNF signaling pathway. Additionally, bioinformatics analysis pinpointed the Traf5-p38 axis as a critical signaling pathway. In vivo and in vitro experiments indicated that inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype. In a Transwell co-culture system, BV2 cells treated with LPS + IFN-γ exacerbated the damage of post-OGD oligodendrocytes, which could be rectified through CD36 knockdown in BV2 cells., Conclusions: This study illuminates that the suppression of CD36 mitigates WMI by constraining microglial polarization towards the pro-inflammatory phenotype through the down-regulation of the Traf5-MAPK signaling pathway. Our findings present a potential therapeutic strategy for averting neuroinflammatory responses and ensuing WMI damage resulting from TBI., (© 2024. The Author(s).)

Background: Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers., Methods: This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored., Results: Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy., Conclusions: Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC., (© 2024. The Author(s).)

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd , has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc - 1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin.

Boron nitride nanosheets (BNNS) are expected to be ideal fillers because of their high thermal conductivity and excellent electrical insulation. However, it is still an open challenge to produce BNNS on a large scale using ecofriendly solvents. Here, first, we demonstrate an effective liquid exfoliation method for producing BNNS via utilizing deep eutectic solvents (DES) composed of D,L-menthol and various acids with the assistance of ultrasonication. The results show that the BNNSs with sizes of 1-2 μm in width and 6-8 nm in thickness were successfully exfoliated with a DES formulation of D,L-menthol and decanoic acid. Second, the obtained BNNSs were used for fabricating 1,6-hexanediol diacrylate@polydopamine functionalized BNNS (HDDA@BNNSs-PDA) core-shell microspheres via a Pickering emulsion method. Furthermore, these microspheres were incorporated into a polyvinylidene fluoride (PVDF) matrix to construct 3D thermally conductive networks, leading to a substantial enhancement in the thermal conductivity of the resulting composites. Impressively, the composites with only 25 wt % of BNNS loading reach a high thermal conductivity of 3.20 W/m K, which is a 1500% increase over the pure polymer matrix. This work not only provides a significant way for producing BNNSs ecofriendly but also demonstrates a tactic for constructing 3D thermally conductive networks.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood., Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM., Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM., Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC., 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., (© 2024 Published by Elsevier Ltd.)

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids from Mycobacterium smegmatis , and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic- co -glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis . After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis . Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis ─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

Batteries with intercalation-conversion-type electrodes tend to achieve high-capacity storage, but the complicated reaction process often suffers from confusing electrochemical mechanisms. Here, we reinterpreted the essential issue about the potential of the conversion reaction and whether there is an intercalation reaction in a lithium/sodium-ion battery (LIB/SIB) with the FeP anode based on the evolution of the magnetic phase. Especially, the ever-present intercalation process in a large voltage range followed by the conversion reaction with extremely low potential was confirmed in FeP LIB, while it is mainly the conversion reaction for the sodium storage mechanism in FeP SIB. The insufficient conversion reaction profoundly limits the actual capacity to the expectedly respectable value. Accordingly, a graphene oxide modification strategy was proposed to increase the reversible capacity of FeP LIB/SIB by 99% and 132%, respectively. The results facilitate the development of anode materials with a high capacity and low operating potential.

Cornus officinalis , a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis , both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl 4 , while in vitro HSCs were exposed to transforming growth factor-β (TGF-β). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl 4 -induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and Sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. siRNA experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A comprehensive LC-MS-based lipidomics analysis of Asian sea bass (Lates calcarifer) muscle after dielectric barrier discharge (DBD) atmospheric plasma treatment was performed. Through the analysis, 1500 lipid species were detected, phosphatidylcholine (PC, 27.80%) was the most abundant lipid, followed by triglyceride (TG, 20.50%) and phosphatidylethanolamine (PE, 17.10%). Among them, 125 lipid species were detected and identified as differentially abundant lipids in Asian sea bass (ASB). PCA and OPLS-DA showed that ASB lipids changed significantly after DBD treatment. Moreover, glycerophospholipid metabolism was key metabolic pathways, as PC, PE, and lysophosphatidylcholine (LPC) were key lipid metabolites. The findings concerning fatty acids revealed that the saturated fatty acids (SFA) content of ASB after DBD treatment increased by 8.54%, while the content of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) decreased by 13.77% and 9.16%, respectively. Our study establishes a foundation for the lipid oxidation mechanism of ASB following DBD treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiamei Wang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they 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.)

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33 +1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

An alpha-proteobacterial strain JXJ CY 53  T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53  T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C 18:1 ω7c and C 16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761  T and Sphingomonas hankookensis KCTC 22579  T , respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53  T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53  T  = KCTC 72813  T  = CGMCC 1.17657  T ). JXJ CY 53  T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53  T dissolved organic carbon for growth, and control the growth of JXJ CY 53  T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T ) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs)., (© 2024. The Author(s).)

Remodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not β-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria., Importance: Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while β-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum -infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs., Competing Interests: The authors declare no conflict of interest.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Controlling friction by light field is a low-cost, low-energy, non-polluting method. By applying ultraviolet light on the surface of photosensitive materials, the properties of the friction pairs or lubricant can be influenced, thus achieving the purpose of reducing friction. In this study, TiO 2 , an inorganic photosensitive material, was selected to investigate the modulating effect of light fields on friction lubrication when using polyalphaolefin (PAO) base oil as a lubricant, and the modulation law of light fields on the friction lubrication behavior was investigated under different loads (1-8 N), different speeds (20-380 mm/s), and different viscosities (10.1-108.6 mPa·s) of PAO base oil. The experimental results showed that light treatment could reduce the friction coefficient of PAO4 base oil lubrication from 0.034 to 0.016, with a reduction of 52.9% under conditions of 3 N-load and 56.5 mm/s-speed, and the best regulation effect could be achieved under the mixed lubrication condition. After TiO 2 was treated with ultraviolet light, due to its photocatalytic property, PAO molecules were oxidized and adsorbed on the TiO 2 surface to form an adsorption layer, which avoided the direct contact of rough peaks and thus reduced the friction coefficient. This study combines photosensitivity, photocatalysis, and friction, presenting a method to reduce the friction coefficient by applying a light field without changing the friction pairs or lubricants, which provides a new direction for friction modulation and gives new ideas for practical applications.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP., Competing Interests: The 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 © 2024 Cao, Hu, Ning, Dou, Ding, Wang, Wang, Sang, Yang, Shi, Hao and Han.)

Background: Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear., Methods: We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs . active PsV, untreated PsV vs . treated PsV, and untreated PsA vs . treated PsA., Results: Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4 + T cells, CD16 - NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (T N ) and central memory CD4 + T cells (T CM ) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28 hi CD127 hi CD4 + T CM cells, CD28 hi CD127 hi CD4 + T N cells, and CD16 - NK cells., Conclusion: In the circulation of PsA patients, the T N and CD4 + T CM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets., Competing Interests: The 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 © 2024 Xudong Sang et al.)

Despite strides in immunotherapy, glioblastoma multiforme (GBM) remains challenging due to low inherent immunogenicity and suppressive tumor microenvironment. Converting "cold" GBMs to "hot" is crucial for immune activation and improved outcomes. This study comprehensively characterized a therapeutic vaccination strategy for preclinical GBM models. The vaccine consists of Mannan-BAM-anchored irradiated whole tumor cells, Toll-like receptor ligands [lipoteichoic acid (LTA), polyinosinic-polycytidylic acid (Poly (I:C)), and resiquimod (R-848)], and anti-CD40 agonistic antibody (rWTC-MBTA). Intracranial GBM models (GL261, SB28 cells) are used to evaluate the vaccine efficacy. A substantial number of vaccinated mice exhibited complete regression of GBM tumors in a T-cell-dependent manner, with no significant toxicity. Long-term tumor-specific immune memory is confirmed upon tumor rechallenge. In the vaccine-draining lymph nodes of the SB28 model, rWTC-MBTA vaccination triggered a major rise in conventional dendritic cell type 1 (cDC1) 12 h post-treatment, followed by an increase in conventional dendritic cell type 2 (cDC2), monocyte-derived dendritic cell (moDC), and plasmacytoid dendritic cell (pDC) on Day 5 and Day 13. Enhanced cytotoxicity of CD4+ and CD8+ T cells in vaccinated mice is verified in co-culture with tumor cells. Analyses of immunosuppressive signals (T-cell exhaustion, myeloid-derived suppressor cells (MDSC), M2 macrophages) in the GBM microenvironment suggest potential combinations with other immunotherapies for enhanced efficacy. In conclusion, the authors findings demonstrate that rWTC-MBTA induces potent and long-term adaptive immune responses against GBM., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect of systemic therapy and radiation therapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC., Methods and Materials: This retrospective observational study analyzed the medical records of 194 patients with Barcelona Clinic Liver Cancer stage C HCC who were admitted to our center from August 2018 to June 2022 and received ICIs combined with antiangiogenic therapy as the first-line treatment. Patients who were administered RT for tumor thrombus or symptomatic metastases within 8 weeks of the commencement of combination therapy were allocated to the RT group, whereas those who did not receive RT were assigned to the non-radiation therapy (NRT) group. Propensity score matching was used to mitigate selection bias. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate, disease control rate (DCR), local PFS, out-of-field PFS, and treatment-related adverse events., Results: A total of 76 patients diagnosed with advanced-stage HCC and treated with ICIs and antiangiogenic therapy were included in the study, with 33 patients in the RT group and 43 patients in the non-RT group. After propensity score matching, 29 matched patient pairs were generated. The median follow-up was 15.5 months, and the RT sites were mainly located on the tumor thrombus (55.2%) and extrahepatic metastatic lesions (48.3%). The median PFS was 8.3 months (95% CI, 5.4-11.3) in the RT group and 4.2 months (95% CI, 3.4-5.0) in the NRT group (P < .001). The median OS was not reached in the RT group and was 9.7 months (95% CI, 4.1-15.3) in the NRT group (P = .002). The objective response rate was 75.9% (95% CI, 56.5-89.7) in the RT group and 24.1% (95% CI, 10.3-43.5) in the NRT group (P < .001). The DCR was 100% in the RT group and 75.9% (95% CI, 56.5-89.7) in the NRT group (P = .005). The median local PFS and out-of-field PFS were 13.2 months (95% CI, 6.3-20.1) and 10.8 months (95% CI, 7.0-14.7), respectively. RT was an independent prognostic factor for PFS (hazard ratio = 0.33; 95% CI, 0.17-0.64; P < .001) and OS (hazard ratio = 0.28; 95% CI, 0.11-0.68; P = .005), respectively. The rates of any grade treatment-related adverse events were similar between the 2 groups., Conclusions: In comparison to the combination of ICIs and antiangiogenic therapy, the inclusion of RT has been observed to improve the DCR and survival outcomes in patients with advanced-stage HCC. The safety profile of this triple therapy was satisfactory., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Kudzu, a plant known for its medicinal value and health benefits, is typically consumed in the form of starch. However, the use of native kudzu starch is limited by its high pasting temperature and low solubility, leading to a poor consumer experience. In this study, kudzu starch was treated using six modification techniques: ball milling, extrusion puffing, alcoholic-alkaline, urea-alkaline, pullulanase, and extrusion puffing-pullulanase. The results of the Fourier transform infrared spectrum showed that the intensity ratio of 1047/1022 cm -1 for the modified starches (1.02-1.21) was lower than that of the native kudzu starch (1.22). The relative crystallinity of modified kudzu starch significantly decreased, especially after ball milling, extrusion puffing, and alcoholic-alkaline treatment. Furthermore, scanning electron microscopy and confocal laser scanning microscopy revealed significant changes in the granular structures of the modified starches. After modification, the pasting temperature of kudzu starch decreased (except for the urea-alkaline treatment), and the apparent viscosity of kudzu starch decreased from 517.95 Pa·s to 0.47 Pa·s. The cold-water solubility of extrusion-puffing and extrusion puffing-pullulanase modified kudzu starch was >70 %, which was significantly higher than that of the native starch (0.11 %). These findings establish a theoretical basis for the potential development of instant kudzu powder., 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. Published by Elsevier B.V.)

Background: Cold plasma exhibits broad applicability in the realm of fish sterilization and preservation. The combination process of plasma-activated water and dielectric barrier discharge (PAW-DBD) was optimized, and its disinfection effects on bass fillets were studied., Results: The best conditions for disinfection of PAW-DBD were as follows. Bass fillets were soaked in PAW for 150 s, and then treated by DBD system at 160 kV for 180 s. The total viable count (TVC) reduced by 1.68 log CFU g -1 . On the 15th day of refrigerated storage, TVC of PAW-DBD group was 7.01 log CFU g -1 , while the PAW and DBD group exhibited a TVC of 7.02 and 7.01 log CFU g -1 on day 12; the TVC of the control group was 7.13 log CFU g -1 on day 6. The sensory score, water-holding capacity, and 2-thiobarbituric acid reactive substance values of the PAW-DBD group were significantly higher than those of PAW and DBD group (P < 0.05), whereas the TVC, Pseudomonas spp. count, and pH of the group were significantly lower (P < 0.05) during refrigerated storage., Conclusion: PAW-DBD treatment can enhance the disinfection effect, maintain good quality, and extend the storage period of bass fillets. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC., (© 2024. The Author(s).)

Background: Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts healthy development of the longan industry. Therefore, identifying relevant genes and analysing their regulatory mechanism are essential for scientific research and longan industry development., Results: DlLFY (Dimocarpus longan LEAFY) contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all tissues tested, except for the leaf, pericarp, and pulp, with the highest expression occurring in flower buds. Expression of DlLFY was significantly upregulated at the early flower induction stage in "SX" ("Shixia"). The results of subcellular localization and transactivation analysis showed that DlLFY is a typical transcription factor acting as a transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and rosette leaf number and area in transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may have binding sites and be putative target genes. Among these five flower-related genes, only AtTFL1 (terminal flower 1) was strongly inhibited in transgenic lines., Conclusion: Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by interacting with TFL1., (© 2024. The Author(s).)

Tabletop three-dimensional light field display is a kind of compelling display technology that can simultaneously provide stereoscopic vision for multiple viewers surrounding the lateral side of the device. However, if the flat panel light field display device is simply placed horizontally and displayed directly above, the visual frustum will be tilted and the 3D content outside the display panel will be invisible, the large oblique viewing angle will also lead to serious aberrations. In this paper, we demonstrate what we believe to be a new vertical spliced light field cave display system with an extended depth content. A separate optimization of different compound lens array attenuates the aberration from different oblique viewing angles, and a local heating fitting method is implemented to ensure the accuracy of fabrication process. The image coding method and the correction of the multiple viewpoints realize the correct construction of spliced voxels. In the experiment, a high-definition and precisely spliced 3D city terrain scene is demonstrated on the prototype with a correct oblique perspective in 100-degree horizontal viewing range. We envision that our research will provide more inspiration for future immersive large-scale glass-free virtual reality display technologies.

A novel type of electron donor-acceptor system was built from a nitrogen-rich covalent organic framework (PC) and a polyoxometalate (BW 12 ), fabricating a composite material (BW 12 @PC-250), which shows significantly improved photocatalytic H 2 O 2 yield (56.4 μM h -1 ) under full spectrum illumination in pure water, being about 30 times higher than that of PC. This is due to the opening of the electron and proton transport pathway between PC and BW 12 , which paves a new way for POMs to modulate the photocatalytic reactions of COFs.

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift., Competing Interests: FS, XD, JZ, JW, XS, XH, MB No competing interests declared, (© 2023, Song et al.)

The three-dimensional (3D) light field display (LFD) with dense views can provide smooth motion parallax for the human eye. Increasing the number of views will widen the lens pitch, however, resulting in a decrease in view resolution. In this paper, an approach to smooth motion parallax based on optimizing the divergence angle of the light beam (DALB) for 3D LFD with narrow pitch is proposed. DALB is controlled by lens design. A views-fitting optimization algorithm is established based on a mathematical model between DALB and view distribution. Subsequently, the lens is reversely designed based on the optimization results. A co-designed convolutional neural network (CNN) is used to implement the algorithm. The optical experiment shows that a smooth motion parallax 3D image is achievable through the proposed method.

Background: The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored., Methods: A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined., Results: The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii., Conclusion: The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies., (© 2024. The Author(s).)

Circular RNAs (circRNAs) have been identified to be dysregulated in non-small cell lung cancer (NSCLC) and implicated in the progression of this cancer. Here, this work aimed to investigate the role and mechanism of circ&#95;0082374 on NSCLC progression. Levels of circ&#95;0082374, miR-491-5p, GPX4 (glutathione peroxidase 4) and epithelial-mesenchymal transition (EMT)-related proteins were examined by quantitative real-time PCR or western blotting, respectively. Cell proliferation and metastasis were detected using cell counting kit-8, colony formation, EdU, transwell, and Scratch assays. Cell ferroptosis was evaluated by measuring cell survival after the treatment of different ferroptosis inducers or inhibitors, as well as the accumulation of intracellular reactive oxygen species (ROS), ferrous iron (Fe 2+ ) and malondialdehyde (MDA). The binding between miR-491-5p and circ&#95;0082374 or GPX4 was confirmed using dual-luciferase reporter and RNA pull-down assays. In vivo experiments were conducted using murine xenograft assay and immunohistochemistry. Circ&#95;0082374 was a stable circRNA with high expression in NSCLC tissues and cells. Functionally, circ&#95;0082374 silencing suppressed NSCLC cell proliferation and metastasis. Moreover, its down-regulation enhanced ferroptosis by decreasing iron and lipid peroxidation accumulation. Mechanistically, circ&#95;0082374 could indirectly up-regulate GPX4 expression via miR-491-5p, indicating the circ&#95;0082374/miR-491-5p/GPX4 competitive endogenous RNAs (ceRNA) network. Rescue experiments demonstrated that the miR-491-5p/GPX4 axis mediated the regulatory effects of circ&#95;0082374 exerted on NSCLC cells. Moreover, knockdown of circ&#95;0082374 impeded NSCLC growth and EMT via regulating miR-491-5p and GPX4. Circ&#95;0082374 silencing could suppress NSCLC cell proliferation, metastasis and induce ferroptosis through miR-491-5p/GPX4 axis, suggesting a novel therapeutic approach for NSCLC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A dual-mode sensing platform for Pb 2+ was constructed based on the dual optical channels of Au NPs system with the amplification of DNAzyme, and it was successfully applied for Pb 2+ determination in preserved egg with satisfactory results. The presence of Pb 2+ activated the DNAzyme and induced the dispersion change of Au NPs in high salt concentration. The sequent absorption change of Au NPs was translated to the fluorescence change of carbon dots through FRET, and the scattering change was transferred to grey value of images involving the Tyndall effect. Thus, a sensing platform based on fluorescence and colorimetric dual-technique was achieved for Pb 2+ detection, under the optimized conditions. With the assistance of DNAzyme, the linear range of fluorometric and colorimetric method were 2.0 × 10 -14  ∼ 8.0 × 10 -10 mol/L and 2.4 × 10 -13  ∼ 9.5 × 10 -9 mol/L, respectively. The dual-mode sensing platform demonstrated its promising application in the environmental monitoring and food safety field., 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.)