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Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs. Although the spontaneous neuronal regeneration derived from adult NSCs is not significant, understanding how the behaviors of qNSCs are regulated sheds light on stimulating endogenous NSC-based neuronal regeneration. In this review, we mainly focus on the recent progress of the developmental origin and regulatory mechanisms that maintain qNSCs under normal conditions, and that mobilize qNSCs under pathological conditions, hoping to give some insights for future study., (© 2024. The Author(s).)

Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.

Unstable Zn interface with serious detrimental parasitic side-reactions and uncontrollable Zn dendrites severely plagues the practical application of aqueous zinc-ion batteries. The interface stability was closely related to the electrolyte configuration and Zn 2+ depositional behavior. In this work, a unique Zn-ion anchoring strategy is originally proposed to manipulate the coordination structure of solvated Zn-ions and guide the Zn-ion depositional behavior. Specifically, the amphoteric charged ion additives (denoted as DM), which act as zinc-ion anchors, can tightly absorb on the Zn surface to guide the uniform zinc-ion distribution by using its positively charged -NR 4 + groups. While the negatively charged -SO 3 - groups of DM on the other hand, reduces the active water molecules within solvation sheaths of Zn-ions. Benefiting from the special synergistic effect, Zn metal exhibits highly ordered and compact (002) Zn deposition and negligible side-reactions. As a result, the advanced Zn||Zn symmetric cell delivers extraordinarily 7000 hours long lifespan (0.25 mA cm -2 , 0.25 mAh cm -2 ). Additionally, based on this strategy, the NH 4 V 4 O 10 ||Zn pouch-cell with low negative/positive capacity ratio (N/P ratio=2.98) maintains 80.4 % capacity retention for 180 cycles. A more practical 4 cm*4 cm sized pouch-cell could be steadily cycled in a high output capacity of 37.0 mAh over 50 cycles., (© 2024 Wiley-VCH GmbH.)

Accumulating evidence suggests that excess fructose uptake induces metabolic syndrome and kidney injury. Here, we primarily investigated the influence of catalpol on fructose-induced renal inflammation in mice and explored its potential mechanism. Treatment with catalpol improved insulin sensitivity and hyperuricemia in fructose-fed mice. Hyperuricemia induced by high-fructose diet was associated with increases in the expressions of urate reabsorptive transporter URAT1 and GLUT9. Treatment with catalpol decreased the expressions of URAT1 and GLUT9. Futhermore, treatment with catalpol ameliorated renal inflammatory cell infiltration and podocyte injury, and these beneficial effects were associated with inhibiting the production of inflammatory cytokines including IL-1β, IL-18, IL-6 and TNF-α. Moreover, fructose-induced uric acid triggers an inflammatory response by activiting NLRP3 inflammasome, which then processes pro-inflammatory cytokines. Treatment with catalpol could inhibit the activation of NLRP3 inflammasome as well. Additionally, TLR4/MyD88 signaling was activated in fructose-fed mice, while treatment with catalpol inhibited this activation along with promoting NF-κB nuclear translocation in fructose-fed mice. Thus, our study demonstrated that catalpol could ameliorate renal inflammation in fructose-fed mice, attributing its beneficial effects to promoting uric acid excretion and inhibit the activation of TLR4/MyD88 signaling., 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.)

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent., Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS)., Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types., Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer., Competing Interests: The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (© 2024 Zhou et al.)

Ethnopharmacological Relevance: Wuweiganlu (WGL) is a well-known formulation described in the "Four Medical Scriptures of Tibetan medicine", which is mainly used for the treatment of Rheumatoid Arthritis (RA) and other chronic ailments prescribed by Tibetan medicine. Nonetheless, the active constituents present in the water extracts of Wuweiganlu (WGLWE) specifically targeting arthritis treatment are largely unknown., Aim of the Study: The aim of this study is to explore the effects and underlying mechanisms of the active components in WGLWE on RA., Materials and Methods: We utilized ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS) to identify the main chemical compositions of WGLWE. The polarization effect of WGLWE on bone marrow-derived macrophages (BMDM) was determined. A rat model of collagen-induced arthritis (CIA) was established by injecting an emulsion of bovine type II collagen mixed with an equal volume of incomplete Freund's adjuvant into the tail, paw and back of rats. A WGLWE-based ointment was topically applied to the legs and paws of the rats for 30 days. The rats' ankles were photographed to measure the degree of swelling. Micro-CT was used to image the knee joint and paw of rats, and the bone mineral density (BMD) and bone volume fraction (BV/TV) of knee joint in rats were analyzed. High-frequency ultrasound imaging of the rat knee joint was performed to observe knee joint effusion. Further, the serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-10, and arginine (Arg-1) in CIA rats were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) and immunofluorescence (IF) co-staining were employed to detect the expression levels of inflammatory factors in synovium., Results: A total of 28 main components were identified in WGLWE, and these compounds can directly bind to the inflammatory pathway proteins such as JAK2, NFκB and STAT3. In vitro experiments demonstrated that WGLWE promoted the transformation of M1 macrophages into M2 macrophages and suppressed the release of proinflammatory cytokines TNF-α and IL-6. In vivo studies showed that WGLWE effectively reduced ankle swelling, alleviated knee joint effusion, and improved BV/TV while also reducing synovial inflammation levels. Furthermore, WGLWE compounds induced the transition of M1-type macrophages to M2-type macrophages in synovial tissue, resulting in decreased secretion of inflammatory factors TNF-α, WGLWE improved the synovial inflammatory state., Conclusion: Our results indicated that WGLWE alleviated joint inflammation in CIA rats and the underlying mechanism may be related to inducing the transformation of bone marrow-derived M1 macrophages to M2 macrophages, leading to an increase in the secretion of anti-inflammatory factors and a decrease in pro-inflammatory factors. Therefore, WGLWE may be used as a potential herbal preparation for the treatment of RA., Competing Interests: Declaration of competing interest All authors state that we have no known competing financial interests or personal relationships that might affect the work reported in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss., Methods: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients., Results: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients., Conclusion: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays., Methods: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression was correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion and prompt apoptosis and G1 arrest of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting., Results: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown., Conclusion: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Water-induced parasitic reactions and uncontrolled dendritic Zn growth are long-lasting tricky problems that severely hinder the development of aqueous zinc-metal batteries. Those notorious issues are closely related to electrolyte configuration and zinc-ion transport behavior. Herein, through constructing aligned dipoles induced electric-field on Zn surface, both the solvation structure and transport behavior of zinc-ions are fundamentally changed. The vertically ordered zinc-ion migration trajectory and gradually concentrated zinc-ion achieved inside the polarized electric-field remarkably eliminate water related side-reactions and Zn dendrites. Zn-metal under the polarized electric-field demonstrated significantly improve reversibility and a dendrite-free surface with strong (002) Zn deposition texturing. Zn||Zn symmetric cell delivers greatly prolonged lifespan up to 1400 h (17 times longer than that of the cell based on bare Zn) while the Zn||Cu half-cell demonstrate ultrahigh 99.9% coulombic efficiency. NH 4 V 4 O 10 ||Zn half-cell delivered exceptional-high 132 mAh g -1 capacity after ultralong 2000 cycles (≈100% capacity retention). In addition, MnO 2 ||Zn pouch-cell under aligned dipoles induced electric-field maintains 87.9% capacity retention after 150 cycles under practical condition of high MnO 2 mass loading (≈10 mg cm -2 ) and limited N/P ratio. It is considered that this new strategy can also be implemented to other metallic batteries and spur the development of batteries with long-lifespan and high-energy-density., (© 2023 Wiley-VCH GmbH.)

Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4 + T cells and loss of immune tolerance. However, the involvement of CD8 + T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single-cell RNA sequencing. This is observed that CD8 + CD27 + CXCR3 - T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8 + CD27 + CXCR3 - T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin-2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score-related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8 + CD27 + CXCR3 - T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study aims to achieve the sustainable utilization of waste glass resources through an investigation into the influence of three types of admixtures, namely waste glass powder (WGP) (G), waste glass powder-slag (G-S), and waste glass powder-fly ash (G-F), on the mechanical properties and durability performance of waste glass concrete. The experimental results demonstrate that the exclusive use of WGP as an admixture led to the relatively poor early compressive strength of the concrete, which decreased with an increase in dosage. However, at medium to long curing ages, the strength of the waste glass concrete could equal or even surpass that of ordinary concrete. When dual admixtures were employed, the G-S group exhibited higher compressive strength compared to the G-F group. Specifically, within the G-S group, a glass powder dosage of 15% yielded higher compressive strength, and after 180 days, the dual admixture groups exhibited greater strength than ordinary concrete (G0); the compressive strength of the tG1S1 group was 44.57 MPa, and that of the G0 group was 40.07 MPa. The chloride ion diffusion coefficient showed a varying trend with an increase in WGP dosage, initially decreasing and then increasing. The concrete's resistance to erosion was maximized when the glass powder dosage reached 30%. As the WGP dosage increased, the overall frost resistance decreased. For a total dosage of 30%, the optimal glass powder dosage in both G-S and G-F groups was found to be 15%.

During development, apoptosis removes redundant cells and ensures proper organ morphogenesis. Necrosis is long known as an adult-bound inflammatory and pathologic cell death. Whether there exists physiological necrosis during early development has been speculated but yet clearly demonstrated. Here, we report evidence of necroptosis, a type of programmed necrosis, specifically in perivascular cells of cerebral cortex and skin at the early stage of development. Phosphorylated Mixed Lineage Kinase Domain-Like protein (MLKL), a key molecule in executing necroptosis, co-expressed with blood endothelial marker CD31 and venous-lymphatic progenitor marker Sox18. Depletion of Mlkl did not affect the formation of blood vessel network but increased the differentiation of venous-lymphatic lineage cells in postnatal cerebral cortex and skin. Consistently, significant enhancement of cerebrospinal fluid diffusion and lymphatic drainage was found in brain and skin of Mlkl -deficient mice. Under hypobaric hypoxia induced cerebral edema and inflammation induced skin edema, Mlkl mutation significantly attenuated brain-blood-barrier damage and edema formation. Our data, for the first time, demonstrated the presence of physiological vascular-associated necroptosis and its potential involvement in the development of venous-lymphatic vessels., 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 © 2023 Meng, Zhao, Li, Fan, Yi, Meng, Wang, Fu, Wu and Wang.)

Metallic Zn represents as a primary choice in fabricating various aqueous Zn-ion batteries (ZIBs), however challenging issues including dendrite growth and parasitic reactions at the anode/electrolyte interface, considerably hamper its practical implementation in large-scale energy storage. Herein, we report a low-cost multifunctional ion rectifier (IRT) as an artificial intermediate to reform Zn anode, which can practically eliminate the above issues. The hydrophobic shell (polyvinylidene difluoride) can suppress Zn interfacial corrosion with an inhibition efficiency of 94.8% by repelling water molecules from the bulk electrolyte. Additionally, negatively-charged ion channels inside the zincophilic core (ultrathin vermiculite sheets) induce de-solvating redistribution effect on Zn 2+ ions flux, enabling a high ions transference number (0.79) for dendrite-free Zn deposition. This leads to exceptional Zn/Zn 2+ reversibility in metallic Zn with IRT stabilization. The remarkable Coulombic efficiency (99.8%, 2000 cycles) for asymmetrical batteries, and a long lifespan (1600 h) with ultrahigh cumulative capacity of 2400 mAh cm -2 for symmetrical batteries, are successfully achieved. More encouragingly, the Zn//NH 4 V 4 O 10 pouch cell retains 94.3% of its original capacity after 150 cycles at 1 A g -1 . We believe that this low-cost and high-efficiency tactic could pave a promising path for anode surface modification., Competing Interests: Conflict of Inerest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objectives: Rheumatoid arthritis (RA) is a disease characterised by bone destruction and systemic inflammation, and interleukin-6 (IL-6) is a therapeutic target for treating it. The study aimed at investigating the sources of IL-6 and the influence of hypoxia-inducible factor-1α (HIF-1α) on IL-6 production by B cells in RA patients., Methods: The phenotype of IL-6-producing cells in the peripheral blood of RA patients was analysed using flow cytometry. Bioinformatics, real-time polymerase chain reaction, Western blot and immunofluorescence staining were used to determine the IL-6 production and HIF-1α levels in B cells. A dual-luciferase reporter assay and chromatin immunoprecipitation were used to investigate the regulatory role of HIF-1α on IL-6 production in human and mouse B cells., Results: Our findings revealed that B cells are major sources of IL-6 in the peripheral blood of RA patients, with the proportion of IL-6-producing B cells significantly correlated with RA disease activity. The CD27 - IgD + naïve B cell subset was identified as the typical IL-6-producing subset in RA patients. Both HIF-1α and IL-6 were co-expressed by B cells in the peripheral blood and synovium of RA patients, and HIF-1α was found to directly bind to the IL6 promoter and enhance its transcription., Conclusion: This study highlights the role of B cells in producing IL-6 and the regulation of this production by HIF-1α in patients with RA. Targeting HIF-1α might provide a new therapeutic strategy for treating RA., Competing Interests: The authors report no conflicts of interest., (© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Lithium-metal shows promising prospects in constructing various high-energy-density lithium-metal batteries (LMBs) while long-lasting tricky issues including the uncontrolled dendritic lithium growth and infinite lithium volume expansion seriously impede the application of LMBs. In this work, it is originally found that a unique lithiophilic magnetic host matrix (Co 3 O 4 -CCNFs) can simultaneously eliminate the uncontrolled dendritic lithium growth and huge lithium volume expansion that commonly occur in typical LMBs. The magnetic Co 3 O 4 nanocrystals which inherently embed on the host matrix act as nucleation sites and can also induce micromagnetic field and facilitate a targeted and ordered lithium deposition behavior thus, eliminating the formation of dendritic Li. Meanwhile, the conductive host can effectively homogenize the current distribution and Li-ion flux, thus, further relieving the volume expansion during cycling. Benefiting from this, the featured electrodes demonstrate ultra-high coulombic efficiency of 99.1% under 1 mA cm -2 and 1 mAh cm -2 . Symmetric cell under limited Li (10 mAh cm -2 ) inspiringly delivers ultralong cycle life of 1600 h (under 2 mA cm -2 , 1 mAh cm -2 ). Moreover, LiFePO 4 ||Co 3 O 4 -CCNFs@Li full-cell under practical condition of limited negative/positive capacity ratio (2.3:1) can deliver remarkably improved cycling stability (with 86.6% capacity retention over 440 cycles)., (© 2023 Wiley-VCH GmbH.)

Mobile ad hoc networks (MANETs) are self-configuring networks of wireless nodes, i.e., mobile devices. Since communications in MANETs occur via wireless channels, it is of significance to secure communications among wireless and mobile nodes. Group key management, as a widely used method for securing group communications, has potentially been used in MANETs for years. Most recently, a secure receiver-unrestricted group key management scheme for MANETs has been proposed, which is used to establish a secure channel among a group of wireless nodes without a trusted dealer, which has some advantages such as eliminating the certificate management problem and receiver restriction. However, a formal security analysis of this scheme is still lacking. Therefore, in this paper, we propose the complete security proof to demonstrate that the scheme satisfies the essential security properties including authentication, message confidentiality, known-key security and dynamic secrecy. We also give a brief discussion about the efficiency of the scheme.

Objective: To deliver a comprehensive picture of the landscape and changing trend of trials and approvals on targeted anticancer drugs in China from 2012 to 2021., Methods: Trials, investigated products, and listed drugs were acquired from national databases. The status quo, changing trend of absolute number, and proportion of targeted trials, products, and drugs, as well as the corresponding difference between domestic and foreign companies were analyzed., Results: A total of 2,632 trials on 1,167 targeted antitumor drugs were identified, accounting for 81.5% of all registered trials. The number and proportion of trials on targeted drugs increased steadily, with an average growth rate of 36.0% and 6.2%, respectively. A similar growth trend was observed in the number (33.7%) and proportion (13.8%) of targeted drugs. Targeted drugs and trials owned by domestic companies accounted for a higher proportion than that by foreign companies (80.5% vs. 19.5%; 83.2% vs. 16.8%, respectively), and the growing trend for both targeted drugs (13.8% vs. 5.7%) and trials (13.8% vs. 33.7%) owned by domestic companies was faster. The proportion of targeted drug trials (80.5% vs. 85.6%) and multicenter trials (6.0% vs. 69.9%) initiated by domestic companies was lower than that by foreign companies, with the gap gradually narrowing. Among the identified 18 targets of the 126 immune drugs under development, only one globally new target was found., Conclusions: Research and development of targeted antitumor drugs in China are booming and advancing rapidly, and domestic enterprises have become the pillar. Encouraging genomics activities and establishing incentives and public-private collaboration frameworks are crucial for innovation-oriented drug development in China., Competing Interests: The authors declare that they have no conflict of interests., (© 2023 Chinese National Cancer Center. Published by Elsevier B.V.)

Objectives: This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes., Methods: We included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls. Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores and outcomes were then analysed., Results: The proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all P < 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (neu-dominant group), group 2 had the highest percentage of monocytes (mono-dominant group) and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (P = 0.001 and P = 0.0091). During the 24.6 (15.2) months of follow-up, the highest total number of disease flares occurred in group 3 (P < 0.0001)., Conclusion: Hierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Older adults are a growing segment of oncology population in China and beyong. However, older cancer patients were vastly underrepresented in clinical trial. To facilitate that all patients with cancer have equal access to the cutting edging treatment and receive evidence-based medication in mainland China, it's of particular importance to fully grasp the proportion of upper age restriction in cancer clinical trials, as well as associated factors., Methods: Based on clinical trials registered on the China Food and Drug Administration Registration and Information Disclosure Platform, we sought to characterize the overall proportion and trajectory of upper age-restriction among registered cancer drug trials in mainland China from 2009 to 2021, and potential influencing factors were determined by multivariate logistic regression., Results: According to the 3485 trials, upper age restriction proportion of cancer drug trials for patients over 65 years and 75 years was 18.8% (95% CI = 17.5%-20.1%) and 56.5% (95% CI = 51.3%-54.6%), respectively. Phase IV trials, international multicenter trials, or trials initiated by global companies seldom excluded patients over 65 years compared with phase I trials, domestic trials and trials initiated by Chinese enterprise, similar for 75 years and above. Both of 65 and 75 years old age limit sponsored by domestic enterprises showed slowly downward trend, while no such trend was observed for that of foreign companies. Solution to upper age eligibility of cancer drug trials was also provided., Conclusions: Although there is a certain downward trend, use of eligibility criteria that explicitly exclude older cancer patients in mainland China was remarkably high, especially for trials initiated by domestic enterprise, domestic trials and early-phase trials. Action is urgently needed to promote treatment equity in the older patients while obtaining adequate evidence in clinical trials., (© 2023. The Author(s).)

In this study, based on the comparison of two counterparts [Mn- and Cr-modified CeO 2 nanobelts (NBs)] with the opposite effects, some novel mechanistic insights into the ethyl acetate (EA) catalytic combustion over CeO 2 -based catalysts were proposed. The results demonstrated that EA catalytic combustion consisted of three primary processes: EA hydrolysis (C-O bond breakage), the oxidation of intermediate products, and the removal of surface acetates/alcoholates. Rapid EA hydrolysis typically occurs on surface acid/base sites or hydroxyl groups, and the removal of surface acetates/alcoholates resulting from EA hydrolysis is considered the rate-determining step. The deposited acetates/alcoholates like a shield covered the active sites (such as surface oxygen vacancies), and the enhanced mobility of the surface lattice oxygen as an oxidizing agent played a vital role in breaking through the shield and promoting the further hydrolysis-oxidation process. The Cr modification impeded the release of surface-activated lattice oxygen from the CeO 2 NBs and induced the accumulation of acetates/alcoholates at a higher temperature due to the increased surface acidity/basicity. Conversely, the Mn-substituted CeO 2 NBs with the higher lattice oxygen mobility effectively accelerated the in situ decomposition of acetates/alcoholates and facilitated the re-exposure of surface active sites. This study may contribute to a further mechanistic understanding into the catalytic oxidation of esters or other oxygenated volatile organic compounds over CeO 2 -based catalysts.

Assemblies of as called "chitosan hydrogel-liposome" are expected for overcoming the burst effect in drug release from chitosan (CS) hydrogels. Herein, a hydrogel delivery system made of chitosan incorporated fatty acid vesicles was constructed for protective sustained release of curcumin (Cur). The curcumin was encapsulated in the prepared oligo-conjugated linoleic acid vesicles (OCLAVs), and then the drug-embedded vesicles were constructed to Cur-OCLAVs-CS hydrogels with CS solution. The fabricated Cur-OCLAVs-CS hydrogel was fluidic at room temperature and could be rapidly gelled at 37 °C. Morphology study proves that the OCLAVs stayed as nano-vesicles in the gel. The Cur-OCLAVs-CS hydrogels effectively declined the burst effect with enhanced antioxidant activity. The Cur (400 μM)-OCLAVs-CS gel presented a cumulative release rate of 51.23 % of curcumin in 96 h, comparing to 93.37 % of that from the Cur-CS gel. Moreover, the corporation of OCLAVs and CS made the gel exhibited strong synergistic effect on the antioxidant activity, with an enhancement of up to 148.1 % on the ferric reducing power. Therefore, the hydrogel carrier made of incorporated fatty acid vesicles-chitosan can be served as an injectable or 3D printable drug delivery system, which may provide a hint to overcome the burst effect that existed in chitosan and other polysaccharide-based gels., 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 © 2022 Elsevier B.V. All rights reserved.)

The aim of this Policy Review was to compare China's overall and synchronous participation in clinical trials for innovative anticancer drugs with that of the USA, the EU, Japan, and South Korea, and to assess changes in the participation rate trends in these five regions. Relevant data from the top 20 international pharmaceutical companies from 2011 to 2021 were systematically collected from the Trialtrove and Pharmaprojects databases. Among the 8260 trials for 954 new anticancer drugs identified, China was involved in 8·8% of the trials and with 20·4% of the drugs being trialled. These participation rates are significantly lower than those for South Korea (14·5% of trials and 36·3% of drugs), Japan (16·1% of trials and 38·7% of drugs), the EU (40·6% of trials and 67·7% of drugs), and the USA (65·7% of trials and 91·2% of drugs; p&lt;0·0001 for all). Similar results were found for the synchronous participation rate, defined as the proportion of drugs or trials at the highest development stage internationally, for the 803 tested drugs, which ranged from 9·0% in China to 87·7% in the USA. China's participation rate in early phase trials (4·4%) and in synchronous trials (5·4%) was even lower, in stark contrast to that of the USA (66·1% for early phase trials and 89·1% for synchronous trials). The fastest growing annual rate of participation in trials was observed in China (15·7%), followed by South Korea (8·2%) and Japan (6·8%); no change was detected in the USA or the EU. This Policy Review shows that Chinese participation in the clinical development of innovative cancer drugs by international pharmaceutical companies has increased over the past decade, but an obvious gap persists in comparison with the USA, the EU, Japan, and South Korea, especially in its synchronous participation and early participation rates., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior distribution and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist approach has dominated medical studies, Bayesian approach has been more and more widely recognized by its flexibility and efficiency. Research and development (R&D) on anti-cancer new drugs have been so hot globally in recent years in spite of relatively high failure rate. It is the common demand of pharmaceutical enterprises and researchers to identify the optimal dose, regime and right population in the early-phase R&D stage more accurately and efficiently, especially when the following three major changes have been observed. The R&D on anticancer drugs have transformed from chemical drugs to biological products, from monotherapy to combination therapy, and the study design has also gradually changed from traditional way to innovative and adaptive mode. This also raises a number of subsequent challenges on decision-making of early R&D, such as inability to determine MTD, flexibility to deal with delayed toxicity, delayed response and dose-response changing relationships. It is because of the above emerging changes and challenges that the Bayesian approach is getting more and more attention from the industry. At least, Bayesian approach has more information for decision-making, which could potentially help enterprises achieve higher efficiency, shorter period and lower investment. This study also expounds the application of Bayesian statistics in the early R&D on anticancer new drugs, and compares and analyzes its idea and application scenarios with frequentist statistics, aiming to provide macroscopic and systematic reference for all related stakeholders.
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Background: Unsaturated fatty acids used to form unstable micro-vesicles, while conjugate linoleic acid (CLA)-sodium dodecyl sulfate (SDS) can self-assembly to stable nano-conjugate linoleic acid vesicles (nano-CLAVs). Generally, micro-capsule could geometrically provide higher loading capacity but also generate concerns in construction convenience, sustained release, bioaccessibility and stability. Hence there is a contradiction between loading capacity and encapsulation efficiency. Therefore, the study of the factors that decide the capsule size falling in nano or micron size with same capsule material would be a benefit to food or drug delivery science., Results: The micron- and nano-CLAVs were constructed for encapsulation and sustained release of ginsenoside Rg3. The formation mechanism of nano or micron capsule,s the effect of vesicle sizes on encapsulation efficiency, drug loading efficiency and stability of the encapsulated Rg3 were investigated. It was found that with the addition of salt (PBS), the size of CLAVs jumped from nano to micron. Furthermore, the salt concentration is the key factor that decides the vesicle size of nano or micron. The pH at fabrication triggers the vesiculation and dramatically affects the vesicle size over the nano and micron scales., Conclusion: Compared to the nano-CLAVs, micron vesicles enhanced the loading capacity to 137.6% and the encapsulation efficiency to 138.4%, respectively. Meanwhile, the micron-CLAVs performed similar sustained release of Rg3 as the nano-CLAVs did, and was stable for 120 days at room temperature or sustained 98.9% of capsules after centrifuge at 6090 × g for 20 min. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: To systematically summarize the landscape and characteristics of all approved new anticancer drugs for the last 10 years in China and the United States (US) to further inform the trend, current state, and existing gap in the availability and affordability of cancer medicine between the two countries., Methods: Mainly based on the Pharmcube database, a list and detailed information of anticancer drugs approved in China and the United States were acquired. The annual number, time lag, and basic characteristics, including drug type, mechanism, enterprise type, indication population, drug target, and cancer type of approved drugs were compared., Results: Eighty-seven and 118 new anticancer drugs were approved in China and the US, respectively, showing a stable trend in the US, while a significant increase was observed after 2016 in China. Of the 42 cancer medicines launched in both countries, the US took precedence, and the median time lag markedly decreased, from 6.53 years in 2012 to 0.88 years in 2020. A total of 14.4% of drugs were applicable to children in the US, while only 2.3% were applicable in China, and there was no difference in drug type and enterprise. Thirty-one and 43 targets were explored, with respect to 27 and 36 cancer types in China and the US, respectively, during the period. In addition, the expenditure of drugs on PD-1 and PD-L1 in China was generally lower than that in America., Conclusion: The availability of new anticancer drugs has increased dramatically in the past decade, particularly in China. Compared with the US, the launch of new anticancer drugs in China lags behind, but the time lag has been shortened significantly, and better affordability is observed in immune drugs. More attention should be given to differentiated innovation, and unmet medical needs in special populations like childhood tumors, which are important directions of new drug R&D in China., 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 © 2022 Huang, Zhu, Ga, Wu, Meng, Wang, Fang, Tang and Li.)

The frequent occurrence of single-phase grounding faults affects the reliable operation of power systems. When a single-phase grounding fault occurs, it is difficult to accurately identify the fault type because of the weak characterization and subtle distinction between different fault types. Therefore, this paper proposes a single-phase grounding fault type identification method based on the multi-feature transformation and fusion. Firstly, the Hilbert-Huang transform (HHT) was used to preprocess the fault recorded wave data to highlight the characteristics between different fault types. Secondly, the deep learning model ResNet18 and the long short-term memory (LSTM) are designed to extract the complex abstract features and time-series correlation features from the preprocessed data set separately. Finally, it designs a fusion model to combine the advantages of heterogeneous models to identify the type of single-phase grounding fault. Experiments validate that the method is good at fully mining the characteristics of the fault types contained in the fault recorded wave data, so it can identify multiple types of faults with strong robustness and provide a reliable basis for the subsequent formulation of targeted fault-handling measures.

Introduction: Psoriasis is an immune-mediated systemic disease. Neutrophils are enriched in psoriasis lesions and can form neutrophil extracellular traps (NETs) to activate keratinocytes. Receptor-interacting protein kinase RIPK1 and RIPK3 are involved in necroptosis and NET formation., Aim: To elucidate whether RIPK1 regulates circulating neutrophils to form NETs and inflammation in psoriasis., Material and Methods: Blood samples of psoriasis patients ( n = 20) and healthy controls ( n = 20) were detected by flow cytometry. The expression level of RIPK1/3 in isolated circulating neutrophils from psoriasis patients ( n = 17) and healthy controls ( n = 17) was examined by quantitative real-time PCR. SYTOX Green dye and PicoGreen reagent were used to detect NET formation and DNA release in neutrophils under the stimulation of phorbol 12-myristate 13-acetate (PMA) and necrostain-1 (Nec-1). Correlation analysis was performed between RIPK1/3 expression and Psoriasis Area Severity Index (PASI), neutrophil-to-lymphocyte ratio (NLR)., Results: RIPK1 and RIPK3 expression in protein levels were decreased in monocytes and neutrophils from peripheral blood of psoriasis patients. In isolated psoriasis neutrophils, RIPK1 and Caspase8 mRNA were downregulated while RIPK3 and MLKL mRNA were elevated, leading to the necroptosis pathway. In addition, RIPK1-inhitor-necrostatin-1 (Nec-1) enhanced NETosis in psoriasis neutrophils in vitro . More importantly, there is a negative correlation between RIPK1 and psoriasis disease severity., Conclusions: Our data demonstrated that downregulated RIPK1 expression in psoriasis neutrophils may enhance NET generation. RIPK1 may be identified as a novel therapeutic target in psoriasis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Polymeric Pickering emulsifiers may bring new insights to emulsion theory and practice due to their soft characters. Herein, a group of soft Pickering emulsifiers, chitosan-casein hydrophobic peptides nanoparticles (CS-CHP NPs) were prepared with a non-covalent anti-solvent procedure. The CS-CHP NPs provided the contact angles of 37.2°-87.4°, stabilizing O/W or W/O emulsions with enhanced thermal stability, endowing the emulsion with pH and CO 2 /N 2 responsiveness. The emulsifying behavior and mechanism presented by CS-CHP NPs were different from that of ordinary hard Pickering emulsifiers, where the appropriate contact angle was 37.2° instead of 87.4° for stabilizing O/W emulsions. Moreover, the nanoparticles possess antioxidant, antibacterial activities and excellent biocompatibility. DPPH and ABTS scavenging activity of the CS-CHP NPs were >220% of that of CS NPs. The last, the emulsion provided high-efficient encapsulation of curcumin, making the soft Pickering emulsifiers a group candidate for drug delivery in food, cosmetics and pharmaceutical industry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Long non-coding RNAs regulate malignant behaviors of nasopharyngeal carcinoma (NPC). We aim to investigate the roles and mechanisms of long non-coding RNA maternally expressed gene 3 (lnc-MEG3) in NPC., Methods: The expression levels of lnc-MEG3 and sequestosome 1 (SQSTM1) in NPC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell invasion and migration abilities were evaluated using transwell and wound healing assays, respectively., Results: Downregulated lnc-MEG3 expression and upregulated SQSTM1 expression were found in NPC tissues and cells. Overexpression of lnc-MEG3 inhibited invasion, migration, and epithelial-mesenchymal transition in NPC cells. Overexpression of lnc-MEG3 reduced the expression level of SQSTM1, and SQSTM1 expression was inversely correlated with lnc-MEG3 level in NPC tissues. Besides, overexpression of SQSTM1 reversed the effects of lnc-MEG3 overexpression. Moreover, knockdown of lnc-MEG3 enhanced NPC progression while its effects were eased by SQSTM1 silence., Conclusion: Lnc-MEG3 inhibits malignant behaviors by regulating SQSTM1 expression. It may serve as a therapeutic target to treat NPC., (© 2021 Wiley Periodicals LLC.)

MXenes are a new class of two-dimensional (2D) materials with promising applications in many fields because of their layered structure and unique performance. In particular, the physical barrier properties of two-dimensional nanosheets make them suitable as barriers against hydrogen. Herein, MXene coatings were prepared on pipe steel by a simple spin-coating process with a colloidal suspension. The hydrogen resistance was evaluated by electrochemical hydrogen permeation tests and slow strain rate tests, and the corrosion resistance was assessed by potentiodynamic polarization. The results reveal that MXene coatings offer excellent hydrogen resistance and corrosion protection by forming a barrier against diffusion. Experimentally, the hydrogen permeability of the MXene coating is one third of the substrate, and the diffusion coefficient decreases as well. The mechanistic study indicates that the hydrogen resistance of the MXene coatings is affected by the number of spin-coated layers, while the concentration of the d-MXene colloidal suspension determines the thickness of a single coating. However, damage to the sample surface caused by the colloidal suspension that contains H + and F - may limit the improvement of the hydrogen resistance. This paper reveals a new application of 2D MXene materials as a novel efficient barrier against hydrogen permeation and the subsequent alleviation of hydrogen embrittlement in the steel substrate.

Purpose: Different non-pharmacological interventions have been considered and applied to patients with colorectal cancer to improve their quality of life and distress symptoms; however, there is little evidence comparing the effectiveness of these strategies. This review aimed at assessing the effect of non-pharmacological interventions on quality of life, anxiety, and depression scores among patients with colorectal cancer., Methods: A systematic search for articles published until August 1, 2020, in the English language was performed in Medline, EMBASE, Web of Science, and the Cochrane Library; the reference lists of eligible articles were scanned for other potentially eligible publications. A meta-analysis was performed using random-effects models to estimate pooled effect sizes., Results: Twenty studies were included, representing a total of 3438 patients with colorectal cancer. Non-pharmacological interventions were associated with a significant reduction in anxiety (standardized mean difference [SMD] = - 0.157; 95% confidence interval [CI], - 0.312-[- 0.002]) and depression (SMD = - 0.207; 95% CI, - 0.390-[- 0.024]) scores during 5-8 months of follow-up. Subgroup analyses revealed that interventions delivered face-to-face improved patients' quality of life during 1-4 months of follow-up. Moreover, interventions delivered face-to-face but without a behavioral component were associated with improved anxiety scores, whereas interventions with a behavioral component improved the depression scores during 5-8 months of follow-up., Conclusions: Non-pharmacological interventions were associated with reduced anxiety and depression scores, whereas interventions delivered face-to-face were associated with improved quality of life scores in patients with colorectal cancer. Given the few studies and patients included in this meta-analysis, these conclusions should be interpreted with caution., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Searching for novel anode materials to address the issues of poor cycle stability in the aqueous lithium-ion battery system is highly desirable. In this work, ammonium vanadium bronze (NH 4 ) 2 V 7 O 16 with brick-like morphology has been investigated as an anode material for aqueous lithium-ion batteries and Li + /Na + hybrid ion batteries. The two novel full cell systems (NH 4 ) 2 V 7 O 16 ||Li 2 SO 4 ||LiMn 2 O 4 and (NH 4 ) 2 V 7 O 16 ||Na 2 SO 4 ||LiMn 2 O 4 both demonstrate good rate capability and excellent cycling performance. A capacity retention of 78.61 % after 500 cycles at 300 mA g -1 was demonstrated in the (NH 4 ) 2 V 7 O 16 ||Li 2 SO 4 ||LiMn 2 O 4 system, whereas no capacity attenuation is observed in the (NH 4 ) 2 V 7 O 16 ||Na 2 SO 4 ||LiMn 2 O 4 system. The reaction mechanisms of the (NH 4 ) 2 V 7 O 16 electrode and impedance variation of the two full cells were also researched. The excellent cycling stability suggests that layered (NH 4 ) 2 V 7 O 16 can be a promising anode material for aqueous rechargeable lithium-ion batteries., (© 2021 Wiley-VCH GmbH.)

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR -/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients., 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 © 2021 Cao, Meng, Li, Sun, Jiang, Xuan and Chen.)

Strong hydrophilicity of polysaccharide and physicochemical instability of peptides limit application of polysaccharide-peptide mixtures in food industry. In this study, a natural resource platform of polysaccharide-peptide conjugates was constructed through Maillard reaction from chitosan and casein hydrophobic peptide. By choosing the molecular weight and deacetylation degree of chitosan and other reaction parameters, the conjugated chitosan-peptides possess extensive HLB values from 6 to 14 were obtained with grafting degree of 3.10%-15.08%. The conjugates have gained dramatically improved emulsifying ability, and endowed the emulsion higher antioxidant capacity than the peptide, chitosan and the mixture of peptide-chitosan has. Emulsions prepared with all conjugates exhibited long-term stability and strengthened tolerance towards temperature and electrolyte stimuli. This stable emulsion system also provided an effective encapsulation, protection and controlled release of curcumin, which may provide a method for transfer polysaccharides to stable emulsifiers with broader HLB values and application., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to investigate the distributions of lymphocytes in adult onset Still's disease (AOSD) with liver dysfunction, and further prospectively explore whether receptor interacting serine/threonine kinases (RIPKs) in lymphocytes play a role in the pathogenesis of AOSD especially liver involvement., Methods: Seventy-two AOSD patients and 19 cases of healthy controls (HCs) were retrospectively reviewed, the AOSD group was then divided into liver damage (LD) group and non-liver damage (NLD) group, and the distributions of lymphocytes in peripheral blood were analyzed. Another independent 24 AOSD patients and 20 HCs were recruited for prospective study of RIPKs; the RIPKs in peripheral blood lymphocytes were detected by flow cytometry. Liver biopsy specimens were obtained from two AOSD patients and underwent immunochemistry analysis with RIPK1 and RIPK3 antibody., Results: In the retrospective study, AOSD showed significantly abnormal lymphocytes distributions, and disease activity was positively correlated with percentage of CD3 + T cells. LD patients were younger in age and showed higher disease activity score than NLD patients; they had higher frequencies of CD3 + T cells, especially higher CD8 + T cells (all p <0.05). In the prospective study, RIPKs in lymphocytes were significantly higher in AOSD patients than that of HCs, and LD patients also showed higher RIPKs expression than NLD patients. In addition, RIPKs were positively correlated with erythrocyte sedimentation rate (ESR) and disease activity in AOSD patients and LD and NLD subgroups (all p <0.05). Further, RIPKs expression was confirmed in two AOSD patients' liver. ROC curve analysis indicated that RIPKs in lymphocytes (%) could be potential biomarkers in the diagnosis of AOSD and liver damage., Conclusions: Abnormal lymphocytes distributions and RIPKs expression were detected in AOSD. Aberrant expression of RIPKs in lymphocytes might be involved in the pathogenesis of AOSD. RIPKs could be candidate markers for AOSD and liver damage., 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 © 2020 Liu, Guo, Meng, Fang and Lu.)

The use of Paecilomyces tenuipes (P. tenuipes), a Chinese medicinal fungus in scientific research, is limited due to its low adenosine content. To improve adenosine production, the present study investigated the gene network of adenosine biosynthesis in P. tenuipes via transcriptome analysis. Mycelia of P. tenuipes cultured for 24 h (PT24), 102 h (PT102) and 196 h (PT192) were subjected to RNA sequencing. In total, 13,353 unigenes were obtained. Based on sequence similarity, 8,099 unigenes were annotated with known proteins. Of these 8,099 unigenes, 5,123 had functions assigned based on Gene Ontology terms while 4,158 were annotated based on the Eukaryotic Orthologous Groups database. Moreover, 1,272 unigenes were mapped to 281 Kyoto Encyclopedia of Genes and Genomes pathways. In addition, the differential gene expression of the three libraries was also performed. A total of 601, 1,658 and 628 differentially expressed genes (DEGs) were detected in PT24 vs. PT102, PT24 vs. PT192 and PT102 vs. PT192 groups, respectively. Reverse transcription‑quantitative PCR was performed to analyze the expression levels of 14 DEGs putatively associated with adenosine biosynthesis in P. tenuipes. The results showed that two DEGs were closely associated with adenosine accumulation of P. tenuipes. The present study not only provides an improved understanding of the genetic information of P. tenuipes but also the findings can be used to aid research into P. tenuipes.

Background: Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied., Methods: An intravenous injection of Adv-IFN-α (10 mice, 10 × 10 9 vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 10 9 vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour., Results: In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression., Conclusions: Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.

The fouling and stability are two most critical limiting factors for practical applications of surface-enhanced Raman scattering (SERS)-based microfluidic electrophoresis device. Herein, we present a novel biomimetic nanoengineering strategy to achieve a SERS substrate featuring antifouling ability, good stability, and reliable quantitative capability. Typically, by employing tea polyphenol as the reducing agent, the substrate made of silver core-gold shell nanostructures in situ grown on silicon wafer surface is fabricated. The core-shell nanostructures are further embedded with internal standard molecules. Remarkably, the fabricated substrate preserves distinct SERS effects, adaptable reproducibility, and reliable quantitative ability even if the substrate is incubated with 15% H 2 O 2 , 13% HNO 3 , or 10 8  CFU/mL bacteria, or suffered from 12-day continuous vibration at 250 rpm/min in PBS buffer. As a proof-of-concept application, the DNA-functionalized substrate is capable of precise quantification of Hg 2+ with a limit of detection down to ca. 1 pM even in sewage water., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Psoriasis (PS) is a systemic, immune-mediated inflammatory disorder. However, the whole lymphocyte compartment and the potential pathologies of PS have not been fully characterized. In the present study, we examined whole lymphocyte subsets and signal transduction proteins using high-dimensional single-cell mass cytometry and a bioinformatics pipeline for an in-depth characterization of the immune cell subsets and protein profiles involved in pathways in the peripheral blood of patients with PS. We identified 15 major immune cell populations in T cell lineages and characterized various CD3+CD4+ Th and CD3+CD8+ T cytotoxic cell populations simultaneously across 24 leukocyte markers and 7 proteins related to the signal transduction pathways. High-dimensional analysis identified 3 new subsets that are abundant in PS peripheral blood, resembling CD3-CD4+ lymphoid tissue inducer cells, Tc17 cells, and CD8+CXCR3+ Tregs. We confirmed the CD3-CD4+ cells, and their features and functions, in an independent PS cohort. The use of single-cell mass cytometry allows systemic-level characterization of lymphocyte subpopulations and dysregulated signaling pathways in the blood of patients with PS, identifying abnormalities of different immune cell subsets. We validated that the CD3-CD4+ cells had elevated OX40 and decreased FRA2 expression, which were positively associated with the PS area and severity index.

Herein, we present a dual-amplification sensing strategy-based surface-enhanced Raman scattering (SERS) chip, which combines rolling circle amplification (RCA) and polyadenine (PolyA) assembly for sensitive and reproducible determination of the activity of M.SssI, a cytosine-guanine dinucleotide (CpG) methyltransferase (MTase). Typically, in the presence of M.SssI, RCA process is triggered, resulting in long, single-stranded DNA (ssDNA) fragments that are hybridized with thousands of Raman reporters of Cy3. Afterward, the resultant ssDNA fragments are conjugated to SERS-active substrates made of silver core-gold satellite nanocomposites-modified silicon wafer (Ag-Au NPs@Si), with the SERS enhancement factor of ∼5 × 10 6 . The core-satellite nanostructures are assembled relied on the strong affinity of PolyA toward gold/silver surface. Of particular significance, the developed SERS chip displays an ultrahigh sensitivity with a low limit of detection (LOD) of 2.8 × 10 -3 U/mL, which is around 2 orders of magnitude higher than most reported methods. In addition, the constructed chip features a broad detection range covering from 0.05 to 50 U/mL. Besides for the ultrahigh sensitivity and broad dynamic range, the chip also features good reproducibility (e.g., the relative standard deviation (RSD) is less than ∼12%). Taking advantages of these merits, the developed chip is feasible for accurate discrimination of M.SssI with various concentrations spiked in human serum samples with good recoveries ranging from 99.6% to 107%.

The quality of input data in deep learning is tightly associated with the ultimate performance of the machine learner. Taking advantage of the unique merits of surface-enhanced Raman scattering (SERS) methodology in the collection and construction of a database (e.g., abundant intrinsic fingerprint information, noninvasive data acquisition process, strong anti-interfering ability, etc.), herein we set up a SERS-based database of deoxyribonucleic acid (DNA), suitable for artificial intelligence (AI)-based sensing applications. The database is collected and analyzed by silver nanoparticles (Ag NPs)-decorated silicon wafer (Ag NPs@Si) SERS chip, followed by training with a deep neural network (DNN). As proof-of-concept applications, three kinds of representative tumor suppressor genes, i.e., p16, p21, and p53 fragments, are readily discriminated in a label-free manner. Prominent and reproducible SERS spectra of these DNA molecules are collected and employed as input data for DNN learning and training, which enables selective discrimination of DNA target(s). The accuracy rate for the recognition of specific DNA target reached 90.28%.

There currently exists increasing concerns on the development of a kind of high-performance SERS platform, which is suitable for sensing applications ranging from the molecular to cellular (e.g., bacteria) level. Herein, we develop a novel kind of universal SERS chip, made of graphene (G)-silver nanoparticle (AgNP)-silicon (Si) sandwich nanohybrids (G@AgNPs@Si), in which AgNPs are in situ grown on a silicon wafer through hydrofluoric acid-etching-assisted chemical reduction, followed by coating with single-layer graphene via a polymer-protective etching method. The resultant chip features a strong, stable, reproducible surface-enhanced Raman scattering (SERS) effect and reliable quantitative capability. By virtues of these merits, the G@AgNPs@Si platform is capable for not only molecular detection and quantification but also cellular analysis in real systems. As a proof-of-concept application, the chip allows ultrahigh sensitive and reliable detection of adenosine triphosphate (ATP), with a detection limit of ∼1 pM. In addition, the chip, serving as a novel multifunctional platform, enables simultaneous capture, discrimination, and inactivation of bacteria. Typically, the bacterial capture efficiency is 54% at 10 8 CFU mL -1 bacteria, and the antibacterial rate reaches 93% after 24 h of treatment. Of particular note, Escherichia coli and Staphylococcus aureus spiked into blood can be readily distinguished via the chip, suggesting its high potential for clinical applications.

One fundamental issue in public health is the safety of food products derived from plants and animals. A recent study raised a concern that microRNAs, which widely exist in everyday foods, may alter consumers' functions. However, some studies have strongly questioned the likelihood of dietary uptake of functional microRNAs in mammals. Here we use a microRNA gene knockout animal model to show that miR-144/451 null mice can orally uptake miR-451 from a daily chow diet, and ingestion of wild type blood, that contains abundant miR-451, also enhances the level of miR-451 in the circulating blood of knockout mice. Moreover, reducing miR-451 level in miR-144/451 knockout blood by consuming food lacking miR-451 reduces the anti-oxidant capacity of miR-144/451 null red blood cells by targeting the 14-3-3ζ/Foxo3 pathway, while increasing miR-451 level via gavage-feeding of wild type blood increases the anti-oxidant capacity of miR-144/451 null red blood cells. We conclude that 1) some miRNAs in food can pass through the gastrointestinal tract into the blood to affect consumers' function and 2) microRNA knockout animals such as miR-144/451 null mice can acquire the deleted genetic information from daily foods, which might alter the results and conclusions from the studies using such animals., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

The antidiabetic effects of Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 in high fat diet and streptozotocin-induced type 2 diabetic (T2D) rats were evaluated in this study. The strains were separated from Chinese traditional fermented dairy food. Administration of G15 and Q14 for 6 weeks significantly improved the glucose tolerance and reduced the HbA1c levels in T2D rats. The probiotic treatment reduced the intestinal mucosal permeability and improved the epithelial barrier function through modification of the gut microbiota, which in turn lowered circulating LPS and inflammation cytokines, including IL-1β and IL-8, and eventually alleviated the inflammatory status and islet β-cell dysfunction. Combination of Q14 and metformin reversed the thymic atrophy and both G15 and Q14 lowered the circulating IL-6 level, indicating the immune-modulating potential of the strains. Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 provide an insight into the biotherapy application of traditional fermented foods and their functional ingredients in the treatment of diabetes.

To evaluate the immune effect of sulfated glucan from saccharomyces cerevisiae (SGSC) on chickens, two experiments were researched. In vitro experiment, the effects of SGSC on chicken splenic lymphocyte proliferation were determined. The results displayed that SGSC could significantly stimulate chicken splenic lymphocyte proliferation. In vivo experiment, 200 14-day-old chickens were averagely divided into 5 groups. The chickens, except blank control (BC) group, were vaccinated with Newcastle disease (ND) vaccine, repeated vaccination at 28 days old. At the same time of the first vaccination, the chickens in three SGSC groups were injected, respectively, with the SGSC at low, medium and high concentrations, in vaccination control (VC) and BC group, with equal volume of physiological saline, once a day for three successive days. On days 7, 14, 21, 28, 35 and 42 after the first vaccination, the lymphocyte proliferation, serum antibody titer and interleukin-2 (IL-2) and interferon-gamma (IFN-γ) were measured. The results showed that SGSC at suitable dose could significantly promote lymphocyte proliferation, enhance serum antibody titer, and improve serum IL-2 and IFN-γ concentrations. It indicated that SGSC could significantly improve the immune efficacy of Newcastle disease vaccine, and would be as the candidate of a new-type immune adjuvant., (Copyright © 2014. Published by Elsevier B.V.)

Cordyceps militaris polysaccharide (CMP) was prepared by water decoction and ethanol precipitation. The fractional CMP40 and CMP50 were extracted from the CMP solution by stepwise precipitation with ethanol at 40% and 50% of working concentration, respectively. The immune-enhancing activities of two polysaccharides were researched. In vitro experiment, the effects of two polysaccharides on chicken peripheral lymphocyte proliferation were determined by MTT assay. The result displayed that two polysaccharides could significantly stimulate lymphocyte proliferation, the action of CMP40 was significantly or numerically stronger than those of CMP50. In vivo experiment, 320 14-day-old chickens were averagely divided into eight groups. The chickens, except blank control (BC) group, were vaccinated with Newcastle disease vaccine, repeated vaccination at 28 days old. At the same time of the first vaccination, the chickens in three CMP40 fraction groups and three CMP50 fraction groups were injected respectively with the polysaccharide at low, medium and high concentrations, in vaccination control (VC) and BC group, with equal volume of physiological saline, once a day for three successive days. On days 7, 14, 21, 28, 35 and 42 after the first vaccination, the lymphocyte proliferation, serum antibody titre and interferon-gamma and interleukin-4 were measured. The results showed that CMP40 and CMP50 at suitable dose could significantly promote lymphocyte proliferation, enhance serum antibody titre, and improve serum interferon-gamma and interleukin-4 concentrations. It indicated that CMP40 fraction and CMP50 fraction could significantly improve the immune efficacy of Newcastle disease vaccine, and would be as the candidate of a new-type immune adjuvant., (Copyright © 2013 Elsevier B.V. All rights reserved.)