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Abstract Objective Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. Methods Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). Results HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. Conclusion Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Fucoxanthin (Fx) has a unique chemical structure that confers its biological effects and shows potential health benefits. The main purpose of this study was to explore whether Fx could alleviate renal fibrosis in diabetic nephropathy (DN) by regulating p62/Keap1/Nrf2 signaling and improving mitochondrial damage. We found that Fx improved renal function, lipid metabolism and renal fibrosis in STZ-induced diabetic rats and alleviated fibrosis in HG-induced GMCs. And Fx regulated protein levels of p62, Keap1 and Nrf2 in kidneys of diabetic rats and HG-induced GMCs. Fx also upregulated protein levels of LC3 II/LC3 I, SOD1 and HO-1, reversed the over-production of mitochondrial superoxide, promoted the interaction between p62 and Keap1, improved mitochondrial morphology and mitochondrial membrane potential reduction and increased co-localization of p62 or Keap1 with mitochondria in HG-induced GMCs. Molecular docking study indicated the strong binding affinity between compound Fx and p62. Overall, Fx may be developed as a promising functional ingredient to alleviate DN.

Abstract The collection of multiple-channel electrophysiological signals enables a comprehensive understanding of the spatial distribution and temporal features of electrophysiological activities. This approach can help to distinguish the traits and patterns of different ailments to enhance diagnostic accuracy. Microneedle array electrodes, which can penetrate skin without pain, can lessen the impedance between the electrodes and skin; however, current microneedle methods are limited to single channels and cannot achieve multichannel collection in small areas. Here, a multichannel (32 channels) microneedle dry electrode patch device was developed via a dimensionality reduction fabrication and integration approach and supported by a self-developed circuit system to record weak electrophysiological signals, including electroencephalography (EEG), electrocardiogram (ECG), and electromyography (EMG) signals. The microneedles reduced the electrode–skin contact impedance by penetrating the nonconducting stratum corneum in a painless way. The multichannel microneedle array (MMA) enabled painless transdermal recording of multichannel electrophysiological signals from the subcutaneous space, with high temporal and spatial resolution, reaching the level of a single microneedle in terms of signal precision. The MMA demonstrated the detection of the spatial distribution of ECG, EMG and EEG signals in live rabbit models, and the microneedle electrode (MNE) achieved better signal quality in the transcutaneous detection of EEG signals than did the conventional flat dry electrode array. This work offers a promising opportunity to develop advanced tools for neural interface technology and electrophysiological recording.

Abstract Objective The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. Methods We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. Results Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5–25%), normal (25–75%), high (75–95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. Conclusion Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.

Abstract Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.

IntroductionCalcein was used to develop a shell marking method for Potamocorbula laevis.MethodsThe suitable conditions for marking were investigated, including marking concentration, immersion time, and water temperature. The impacts and feasibility of the marking method were assessed based on the survival rate of P. laevis, the success rate of fluorescence marking, marking quality, and alterations in activities of antioxidant enzymes in the digestive gland of the experimental bivalves. Two concentrations of calcein (20 and 50 mg/L) were used and the immersion time included 1 and 2 h, respectively. The experiment was performed in two rounds, with water temperatures of 12.84 ± 0.09 and 24.18 ± 0.04 °C, respectively.Results and discussionThe results indicated that calcein did not significantly impact the survival of P. laevis after 7 d of recovery. The catalase activity and malondialdehyde content in low temperature-marked P. laevis showed significant decreases, and the relative abundances of certain fatty acids also exhibited significant changes within 2 h post exposure to 20 mg/L of calcein. However, these indicators returned to normal levels within 7 d. The marking impact of calcein was proportional to the calcein concentration and immersion time. Higher temperature generated a negative impact on the marking effect of 20 mg/L of calcein, while no obvious impacts were observed for 50 mg/L of calcein. The marking success rates and the recapture rates of P. laevis for in situ tests in the two experimental groups were both 100% and 4.44 ± 1.29% after one month. Also, the recapture marking rates and the marking good rates of the recaptured individuals were both 100%. There were no significant differences between these parameters for 50 and 75 mg/L of calcein. Given the cost and safety of labeling, a strategy in terms of an immersion in 50 mg/L of calcein for 2 h could be considered as an effective in situ labeling scheme for P. laevis. In conclusion, calcein can be employed as a marking method for P. laevis. These findings could be potentially beneficial for development of in situ labeling technology, proliferation as well as release of shellfish in tidal flats and resource conservation.

Short neuropeptide F (sNPF) is a neuropeptide that widely distributed among arthropods. This neuropeptide has been proposed to play pleiotropic roles in insects, but its physiological functions in crustaceans are poorly understood. Here, we cloned the cDNA sequences of sNPF and its putative receptor (sNPFR) from the swimming crab, Portunus trituberculatus, and determined their possible roles during ovarian development. PtsNPF encodes three sNPF mature peptides with a conserved C-terminal “RLRFG” motif. All three PtsNPF peptides concentration-dependently activated PtsNPFR expressed in HEK293T cells, with EC50 values in the nanomolar range. PtsNPF and PtsNPFR transcripts showed a broad distribution among neural and non-neural tissues. During the ovarian development, expression of PtsNPF and PtsNPFR in hepatopancreas and ovary both increased to the highest levels at the late-vitellogenic stage, a period for rapid vitellogenesis. The in vitro experiments further showed that, among the three sNPF peptides, sNPF3 treatments can induce the vitellogenin (Vg) gene and protein levels in the hepatopancreas, as well as the Vg receptor (VgR) gene and protein levels and vitellogenin (Vn) deposition in the ovary. Opposing effects were observed for the dsPtsNPFR treatments, suggesting that PtsNPFR plays a role in the PtsNPF-mediated vitellogenesis. Additionally, it was found that the PtsNPF/PtsNPFR system can activate different second messengers species in hepatopancreas and ovary, suggesting it may act via different G proteins.

Crisp Nile tilapia (Oreochromis niloticus) is a valuable fish product with high muscle firmness and chewiness generated by dietary faba beans (Vicia faba L.). However, the overconsumption of faba bean could induce intestinal inflammation in Nile tilapia due to its endogenous anti-nutritional factors (ANFs). Germination has been cited as an effective method for reducing ANFs in faba beans. But, the effects of germinated faba beans on the tilapia remain unclear. In this report, Nile tilapia were fed a diet supplemented with dry faba beans (FB0), or germinated faba beans (FB5), or a basal diet (control) for 75 days. Thereafter, samples of the fish were examined for textural quality, digestive enzyme activity, histology of the inner intestinal wall, expression of related genes, and composition of intestinal microbes. The hardest fillets were obtained from the FB5 (406.17 ± 42.51 gf) group, followed by the FB0 (301.17 ± 24.70 gf) and control (117.50 ± 8.19 gf) groups. The amylase levels were lower in the FB0 and FB5 groups, whereas the trypsin activities were up to 1.9-fold higher than in the control group. The gene expressions of IL-1β, CCL3, and TNF-α were significantly up-regulated in both the FB0 and FB5 groups, whereas metallothionein expression was down-regulated in the intestine relative to control group. Moreover, expression of IFN-γ and Hsp70 decreased in FB5, but increased in FB0. In particular, the diversity of intestinal microbiota was higher in the FB5 group than in the FB0 group (Fusobacteria abundance significantly decreased from 79.18% to 55.87%, while Proteobacteria abundance decreased from 8.12% to 7.02%), indicating that the intestinal microbiota structure was affected by altered diets. These results indicate that germinated faba bean could be a good substitute for dry faba beans in tilapia culture.

Abstract We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83–1.4), 90-day (HR: 1.03, 95% CI 0.80–1.31) and in-hospital(HR: 1.30, 95% CI 0.90–1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78–5.07), kidney failure (OR: 1.90, 95% CI 1.13–3.18), coagulation failure (OR: 2.55, 95% CI 1.52–4.27), respiratory failure (OR: 1.76, 95% CI 1.15–2.69), and circulatory failure (OR: 2.15, 95% CI 1.27–3.64), and even associated with prolonged the LOS ICU (β: 2.61, 95% CI 1.59–3.62) and LOS hospital (β: 6.59, 95% CI 2.62–10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95–1.29) and CAPS (HR: 1.09, 95% CI 0.86–1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1 ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14 days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.

Abstract NRAS mutations are most frequently observed in hematological malignancies and are also common in some solid tumors such as melanoma and colon cancer. Despite its pivotal role in oncogenesis, no effective therapies targeting NRAS has been developed. Targeting NRAS localization to the plasma membrane (PM) is a promising strategy for cancer therapy, as its signaling requires PM localization. However, the process governing NRAS translocation from the Golgi apparatus to the PM after lipid modification remains elusive. This study identifies GOLGA7 as a crucial factor controlling NRAS’ PM translocation, demonstrating that its depletion blocks NRAS, but not HRAS, KRAS4A and KRAS4B, translocating to PM. GOLGA7 is known to stabilize the palmitoyltransferase ZDHHC9 for NRAS and HRAS palmitoylation, but we found that GOLGA7 depletion does not affect NRAS’ palmitoylation level. Further studies show that loss of GOLGA7 disrupts NRAS anterograde trafficking, leading to its cis-Golgi accumulation. Remarkably, depleting GOLGA7 effectively inhibits cell proliferation in multiple NRAS-mutant cancer cell lines and attenuates NRASG12D-induced oncogenic transformation in vivo. These findings elucidate a specific intracellular trafficking route for NRAS under GOLGA7 regulation, highlighting GOLGA7 as a promising therapeutic target for NRAS-driven cancers.

Abstract Background Temperature is an important environment factor that is critical to the survival and growth of crustaceans. However, the mechanisms by which crustaceans detect changes in temperature are still unclear. The transient receptor potential (TRP) channels are non-selective cation channels well known for properties in temperature sensation. However, comprehensive understandings on TRP channels as well as their temperature sensing functions are still lacking in crustaceans. Results In this study, a total of 26 TRP genes were identified in the swimming crab, Portunus trituberculatus, which can be classified into TRPA, TRPC, TRPP, TRPM, TRPML, TRPN and TRPV. Tissue expression analysis revealed a wide distribution of these TRP genes in P. trituberculatus, and antennules, neural tissues, and ovaries were the most commonly expressed tissues. To investigate the responsiveness of TRP genes to the temperature change, 18 TRPs were selected to detect their expression after high and low temperature stress. The results showed that 12 TRPs showed induced gene expression in both high and low temperature groups, while 3 were down-regulated in the low temperature group, and 3 showed no change in expression in either group. Conclusions This study characterized the TRP family genes in P. trituberculatus, and explored their involvement in response to temperature stress. Our results will enhance overall understanding of crustacean TRP channels and their possible functions.

Abstract To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including “Takayasu Arteritis”, “Tuberculosis”, and “Mycobacterium tuberculosis”, the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48–43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71–28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70–87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25–68.77%) and active TB at 14.40% (95% CI 9.03–20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population.

Phoenix barb (Spinibarbus denticulatus denticulatus) is a notable fish species in South China and is valued for its ecological and economic importance. To elucidate the molecular basis underlying its growth, we collected transcriptome profiles from the brains and livers of individual fish with different growth rates and compared differentially expressed genes (DEGs) at 3 and 9 months after hatching (MAH). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the pathways associated with growth were predominantly enriched in fatty acid biosynthesis, AMPK signaling, PI3K-Akt signaling, estrogen signaling, and protein metabolism. Notably, a greater number of DEGs from the fast-growing group were associated with these pathways at the early growth stage (3 MAH) than at the later stage (9 MAH). Real-time quantitative PCR results further validated that the genes involved in these pathways exhibited higher expression levels in fast-growing samples. This study enhances our understanding of the genetic mechanisms underlying growth rate differences and provides valuable genetic resources for future growth-related molecular breeding programs of phoenix barbs.

Oral diseases include oral cancer, periodontitis, endodontium infection, and caries. The oral cavity is prone to the proliferation of pathogenic bacteria and infectious diseases owing to its unique environment. During the drug-based treatment of oral diseases, saliva can dilute the drug formulation, reduce the interaction between the drug and site of action, and weaken drug efficacy. Therefore, searching an effective drug delivery approach is extremely critical and urgent. Stimuli responsive hydrogels respond to altered environmental conditions under disease states, allowing specific drug delivery. Accordingly, smart drug delivery systems can prolong the duration of drug action, reduce adverse reactions, decrease the frequency of administration, and improve patient compliance, thereby accelerating recovery. In this review, we discuss the different types of stimuli responsive hydrogels for smart drug delivery, focusing on their application in oral disease management. Further, we present current challenges and provide suggestions for future research on stimuli responsive hydrogels for oral disease treatment.

Thiosulfate influences the bioreduction and migration transformation of arsenic (As) and iron (Fe) in groundwater environments. The aim of this study was to investigate the impact of microbially-mediated sulfur cycling on the bioreduction and interaction of As and Fe. Microcosm experiments were conducted, including bioreduction of thiosulfate, As(V), and Fe(III) by Citrobacter sp. JH012–1, as well as the influence of thiosulfate input at different initial arsenate concentrations on the bioreduction of As(V) and Fe(III). The results demonstrate that Citrobacter sp. JH012–1 exhibited strong reduction capabilities for thiosulfate, As(V), and Fe(III). Improving thiosulfate level promoted the bioreduction of Fe(III) and As(V). When 0, 0.1, 0.5, and 1 mM thiosulfate were added, Fe(III) was completely reduced within 9 days, 3 days, 1 day, and 0.5 days, simultaneously, 72.8%, 82.2%, 85.5%, and 90.0% of As(V) were reduced, respectively. The products of As(III) binding with sulfide are controlled by the ratio of As-S. When the initial arsenate concentration was 0.025 mM, the addition of thiosulfate resulted in the accumulation of soluble thioarsenite. However, when the initial arsenate level increased to 1 mM, precipitates of orpiment or realgar were formed. In the presence of both arsenic and iron, As(V) significantly inhibits the bioreduction of Fe(III). Under the concentrations of 0, 0.025, and 1 mM As(V), the reduction rates of Fe(III) were 100%, 91%, and 83%, respectively. In this scenario, the sulfide produced by thiosulfate reduction tends to bind with Fe(II) rather than As(III). Therefore, the competition of arsenic-iron and thiosulfate concentration should be considered to study the impact of thiosulfate on arsenic and iron migration and transformation in groundwater.

In this review, we report investigating photothermal hydrogels, innovative biomedical materials designed for infection control and tissue regeneration. These hydrogels exhibit responsiveness to near-infrared (NIR) stimulation, altering their structure and properties, which is pivotal for medical applications. Photothermal hydrogels have emerged as a significant advancement in medical materials, harnessing photothermal agents (PTAs) to respond to NIR light. This responsiveness is crucial for controlling infections and promoting tissue healing. We discuss three construction methods for preparing photothermal hydrogels, emphasizing their design and synthesis, which incorporate PTAs to achieve the desired photothermal effects. The application of these hydrogels demonstrates enhanced infection control and tissue regeneration, supported by their unique photothermal properties. Although research progress in photothermal hydrogels is promising, challenges remain. We address these issues and explore future directions to enhance their therapeutic potential.

Abstract Background Interstitial pregnancy may still happen even after ipsilateral salpingectomy, resulting in massive hemorrhage. Therefore, the purpose of the study is to identify risk factors associated with interstitial pregnancy following ipsilateral salpingectomy and discuss possible prevention. Methods We conducted a retrospective cohort study in a single, large, university-affiliated hospital. Data of 29 patients diagnosed with interstitial pregnancy following ipsilateral salpingectomy from January 2011 to November 2020 were assigned into the case group (IP group). Whereas there were 6151 patients with intrauterine pregnancy after unilateral salpingectomy in the same period. A sample size of 87 control patients was calculated to achieve statistical power (99.9%) and an α of 0.05. The age, BMI and previous salpingectomy side between the two group were adjusted with PSM at a ratio of 1:3. After PSM, 87 intrauterine pregnancy patients were successfully matched to 29 IP patients. Results After PSM, parous women were more common and intrauterine operation was more frequent in the IP group compared with control group (P

Crisp Nile tilapia (Oreochromis niloticus) is a kind of valuable fish product with high muscle firmness and crispiness texture. However, with the change of physicochemical in crisp Nile tilapia, the frozen storage parameters and quality would be different comparing to normal Nile tilapia. Thus, the aim of this study was to analyze the changes in texture, chemical quality indices and volatile compounds of Nile tilapia fillets during frozen storage. The remaining storage time of the crisp Nile tilapia fillets could be estimated within 120 days. During frozen storage, fillets resulted in softer started at 90-day, and 36.75%, 45.74%, 48.81% and 20.37% reduction of hardness, springiness, gumminess and chewiness were observed at 120-day. Thiobarbituric acid reactive substances (TBARS) for frozen samples showed similar with fresh fillets within 60 days, while the TBARS was 1.97 folds higher than fresh one at 120-day. Low-field nuclear magnetic resonance (LF-NMR) indicated that the water loss of Nile tilapia fillets was significant changed at 120-day, which reduced more than 12.5% water out of weight. The volatile compound analysis showed that more free fatty acid will be detected at 120-day comparing to the fresh fillets. The combined results demonstrated that the crisp Nile tilapia fillets had the best quality before 60 days frozen storage then loss of some quality properties in longer freezing. Thus, these results identified the ideal storage strategy for the preservation of crisp Nile tilapia without affecting sensory appeal and commercial value.

Purpose The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate, noninvasive, and convenient index for predicting delayed graft function (DGF) post-transplantation. Methods In total, 90 brain-dead donor kidneys (training group, n=60; validation group, n=30) examined between August 2020 and November 2022 were recruited in this prospective study. CEUS was performed on the kidneys of brain-dead donors 24 hours before organ procurement and time-intensity curves were constructed. The main measures were arrival time, time to peak, and peak intensity of the kidney segmental arteries, cortex, and medulla. Recipients were divided into DGF and non-DGF groups according to early post-transplant graft function. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance. Results The arrival time of the kidney segmental artery and cortex and the time interval between the time to peak of the segmental artery and cortex were identified as independent factors associated with DGF by multivariate stepwise regression analysis. A new index for the joint prediction model of three variables, the contrast-enhanced ultrasonography/Kidney Donor Profile index (CEUS-KDPI), was developed. CEUS-KDPI showed high accuracy for predicting DGF (training group: AUC, 0.91; sensitivity, 90.5%; specificity, 92.3%; validation group: AUC, 0.84; sensitivity, 75.0%; specificity, 92.3%). Conclusion CEUS-KDPI accurately predicted DGF after kidney transplantation. CEUS may be a potential noninvasive tool for bedside examinations before organ procurement and may be used to predict early renal function after kidney transplants kidneys from donors after brain death.

The neuropeptide corazonin (Crz) exerts diverse physiological effects in insects, yet its role in crustaceans remains elusive. The abundant expression of Crz receptor (CrzR) in the Y-organs of several crustaceans suggests a potential involvement of Crz in regulating ecdysteroid synthesis. In this study, we examined the effects of PtCrz on ecdysteroid synthesis during the molting period of Portunus trituberculatus through PtCrz treatments and PtCrzR silencing. Our results showed that PtCrz peptide stimulates ecdysteroid levels and the gene expression involved in ecdysteroidogenesis both in vitro and in vivo, whereas dsPtCrzR treatments had opposite effects on ecdysteroid levels and associated gene expression. Thus, our study suggests that PtCrz may modulate ecdysteroid synthesis via Y-organ-expressed PtCrzR. Furthermore, we also discovered the involvement of PtCrz/PtCrzR signaling in regulating PtETH expression. Notably, the inhibitory effect of dsPtCrzR on ecdysteroid synthesis or PtETH expression can be reversed by PtCrz treatment, suggesting the potential existence of multiple receptors for PtCrz. This study provides new insights into the function of crustacean Crz and, for the first time, elucidates the presence of a neuropeptide that can stimulate ecdysteroid synthesis in crustaceans.

Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules.

Introduction: Reducing the protein adsorption of nanoparticles (NPs) as drug carriers to slow their rapid clearance by macrophages uptake is a critical challenge for NPs clinical translational applications. Despite extensive research efforts to inhibit cellular uptake, including covering biological agents or surface chemical coatings to impart “stealth” properties to NPs, their stability remains insufficient. Objectives: Developed a novel surface modification technology based on a physical infusion engineering approach to achieve persistent inhibition of protein adhesion and cellular uptake by nanocarriers. Methods: The nanoparticles were prepared based on conventional drug carrier mesoporous silica NPs through a two-step process. A functional nanoscale slippery surface was formed by grafting “liquid-like” brushes on the particles surface, and then a lubricant-entrenched slippery surfaces (LESS) was formed by infusing silicone oil lubricant into the entire surface. Co-incubation with macrophages (in vitro and in vivo) was used to examine the anti-uptake properties of modified NPs. The anti-adhesion properties of LESS coating surfaces to various liquids, proteins and cells were used to analyze the anti-uptake mechanism. Loaded with drugs, combined with tumor models, to evaluate the drug utilization of modified NPs. Results: Relying on the stable and slippery LESS coating, the modified surface could prevent the adhesion of various liquids and effectively shield against the adhesion of proteins and cells, as well as remarkably reduce macrophage cellular uptake in vitro and in vivo. In addition, the LESS coating does not affect cell activity and allows NPs to be loaded with drugs, significantly improving the utilization of drugs in vitro and in vivo. This allows the NPs to reach to the target tumor site for drug delivery without active clearance by macrophages. Conclusion: Our research introduces a new nanocarrier technology to improve anti-biofouling performance and stealth efficiency that will facilitate the development of nanomedicines for clinical transformation applications.

Purpose To examine the accuracy of transperineal magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) in identifying men with prostate cancer (PCa) that has reached a clinically relevant stage. Methods This investigation enrolled 459 males. In 210 of these patients (FB group), transperineal MRI/US fusion-guided biopsies were performed on the suspicious region, and in 249 others, a systematic biopsy (SB) was performed (SB group). We compared these groups using Gleason scores and rates of cancer detection. Results PCa cases counted 198/459 (43.1%), including 94/249 (37.8%) in the SB group and 104/210 (49.5%) in the FB group. FB was associated with higher overall diagnostic accuracy relative to SB (88.5% and 72.3%, P = 0.024). FB exhibited greater sensitivity than SB (88.9% and 71.2%, P = 0.025). The area under the curve for FB and SB approaches was 0.837 and 0.737, respectively, such that FB was associated with an 11.9% increase in accuracy as determined based upon these AUC values. Relative to SB, FB was better able to detect high-grade tumors (GS ≥ 7) (78.85% vs. 60.64%, P = 0.025). Conclusion Transperineal MRI-US fusion targeted biopsy is superior to the systematic one as an approach to diagnosing clinically significant PCa, as it is a viable technical approach to prostate biopsy.

IntroductionMarine epiphytic diatoms are natural diets for multiple marine invertebrates, including sea cucumbers, sea urchins, etc. They also act as bioindicators in marine waters to assess water quality of coastal ecosystems. Material and methodsWe isolated three strains of Navicula and two strains of Nitzschia from macroalgal epiphytes. Combined concentrations of four macroelements, five trace metals, and three vitamins in f/2 medium were optimized for these diatoms using single-factor and orthogonal tests. Results and discussionThe biomass productivities for 4-L enlarged cultures of the five isolated diatoms in their exclusively optimized f/2 media all increased by nearly 10-fold relative to f/2 medium, and that of Navicula-1 and Nitzschia-2 reached the highest, i.e., 29.52 ± 1.98 and 30.68 ± 2.84 g m-2 d-1, respectively. Moreover, the relative abundance of C20:5n3 in the exclusively optimized f/2 medium-cultured Navicula-1 notably rose by 24%, and that in Nitzschia-2 held stable at > 25%. Thus, Navicula-1 and Nitzschia-2 were screened out with outstanding growth traits and improved fatty acid compositions at high levels of combined nitrogen, phosphorus, iron, and silicon. The two diatoms have potential for becoming quality diets for marine aquaculture, and ideal candidates for effective nutrient removal.

Abstract Bioinspired nacre-like structures are effective in toughening materials, yet are difficult to construct in magnesium-ceramic systems. Here, a set of magnesium-MAX phase composites with nacre-like lamellar and brick-and-mortar architectures are fabricated by pressureless infiltration of the magnesium melt into ice-templated Ti3AlC2 ceramic scaffolds. The structure and mechanical properties of the composites are elucidated with a special focus on the effects of the types of architectures (lamellar or brick-and-mortar) and matrices (pure magnesium or AZ91D alloy) on the toughening mechanisms. The nacre-like architectures are found to play a role in blunting the cracks via plastic deformation and microcracking, and shielding the cracks from applied stress by promoting crack deflection and uncracked-ligament bridging mechanisms. These composites achieve a good combination of specific strength and fracture toughness, which are superior to many other reported magnesium-ceramic and nacre-like metal-ceramic composite materials.

Abstract Background Although there are concerns about the association between dermatomyositis (DM) and malignancy, the clinical features in elderly DM patients with lung cancer are largely unknown. Here, we elucidated the clinical features and risk factors of lung cancer in elderly DM patients. Methods The data of elderly DM patients (≥65 years old) with or without lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2016 to November 2022 were retrospectively analyzed. Results Male patients with elderly onset DM (EODM) symptoms were found to be prone to lung cancer (p

Abstract COVID-19 has seriously threatened public health, and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MNs) can damage the stratum corneum to allow passive diffusion of vaccine macromolecules, but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecule delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity, and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is “press and poke, iontophoresis-driven delivery, and immune response”. We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery efficiency. In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection. Moreover, there was little concern about the biosafety of the iontophoresis-driven MN patch. This delivery system has a low cost, is user-friendly, and displays active delivery, showing great potential for vaccine self-administration at home.

Abstract Monitoring human health is of considerable significance in biomedicine. In particular, the ion concentrations in blood are important reference indicators related to many diseases. Microneedle array-based sensors have enabled promising breakthroughs in continuous health monitoring due to their minimally invasive nature. In this study, we developed a microneedle sensing-array integrated system to continuously detect subcutaneous ions to monitor human health status in real time based on a fabrication strategy for assembling planar microneedle sheets to form 3D microneedle arrays. The limitations of preparing 3D microneedle structures with multiple electrode channels were addressed by assembling planar microneedle sheets fabricated via laser micromachining; the challenges of modifying closely spaced microneedle tips into different functionalized types of electrodes were avoided. The microneedle sensing system was sufficiently sensitive for detecting real-time changes in Ca2+, K+, and Na+ concentrations, and it exhibited good detection performance. The in vivo results showed that the ion-sensing microneedle array successfully monitored the fluctuations in Ca2+, K+, and Na+ in the interstitial fluids of rats in real time. By using an integrated circuit design, we constructed the proposed microneedle sensor into a wearable integrated monitoring system. The integrated system could potentially provide information feedback for diseases related to physiological ion changes.

Real-time monitoring of physiological indicators inside the body is pivotal for contemporary diagnostics and treatments. Implantable electrodes can not only track specific biomarkers but also facilitate therapeutic interventions. By modifying biometric components, implantable electrodes enable in situ metabolite detection in living tissues, notably beneficial in invasive glucose monitoring, which effectively alleviates the self-blood-glucose-managing burden for patients. However, the development of implantable electrochemical electrodes, especially multi-channel sensing devices, still faces challenges: (1) The complexity of direct preparation hinders functionalized or multi-parameter sensing on a small scale. (2) The fine structure of individual electrodes results in low spatial resolution for sensor functionalization. (3) There is limited conductivity due to simple device structures and weakly conductive electrode materials (such as silicon or polymers). To address these challenges, we developed multiple-channel electrochemical microneedle electrode arrays (MCEMEAs) via a separated functionalization and assembly process. Two-dimensional microneedle (2dMN)-based and one-dimensional microneedle (1dMN)-based electrodes were prepared by laser patterning, which were then modified as sensing electrodes by electrochemical deposition and glucose oxidase decoration to achieve separated functionalization and reduce mutual interference. The electrodes were then assembled into 2dMN- and 1dMN-based multi-channel electrochemical arrays (MCEAs), respectively, to avoid damaging functionalized coatings. In vitro and in vivo results demonstrated that the as-prepared MCEAs exhibit excellent transdermal capability, detection sensitivity, selectivity, and reproducibility, which was capable of real-time, in situ glucose concentration monitoring.

AREB/ABF (ABA response element binding) proteins in plants are essential for stress responses, while our understanding of AREB/ABFs from orchid species, important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genomes and classified into three groups through phylogenetic analysis, which was further supported with a combined analysis of their conserved motifs and gene structures. The cis-element analysis revealed that hormone response elements as well as light and stress response elements were widely rich in the AREB/ABFs. A prediction analysis of the orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory element (CRE) analysis of their promoter regions. And it revealed that several dominant transcriptional factor (TF) gene families were abundant as potential regulators of these orchid AREB/ABFs. Expression profile analysis using public transcriptomic data suggested that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as a homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that transgenic Arabidopsis overexpressing DcaABI5 could rescue the ABA-insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Femtosecond laser ablation has found wide-ranging applications in the surface structuring of nanoelectronics and nanophotonics devices. Traditionally, the inspection of the fabricated three-dimensional (3D) morphology was performed using a scanning electron microscope or atomic force microscopy in an ex situ manner after processing was complete. To quickly monitor and efficiently optimize the quality of surface fabrication, we developed an in situ method to accurately reconstruct the 3D morphology of surface micro-structures. This method is based on a triangulation optical system that utilizes structured illumination. The approach offers a super-resolution capacity, making it a powerful and non-invasive tool for quick in situ monitoring of surface ablation structures.

Summary: The constant emergence of mutated pathogens poses great challenges to the existing vaccine system. A screening system is needed to screen for antigen designs and vaccination strategies capable of inducing cross-protective immunity. Herein, we report a screening system based on DNA vaccines and a micro-electroporation/electrophoresis system (MEES), which greatly improved the efficacy of DNA vaccines, elevating humoral and cellular immune responses by over 400- and 35-fold respectively. Eighteen vaccination strategies were screened simultaneously by sequential immunization with vaccines derived from wildtype (WT) SARS-CoV-2, Delta, or Omicron BA.1 variant. Sequential vaccination of BA.1-WT-Delta vaccines with MEES induced potent neutralizing antibodies against all three viral strains and BA.5 variant, demonstrating that cross-protective immunity against future mutants can be successfully induced by existing strain-derived vaccines when a proper combination and order of sequential vaccination are used. Our screening system could be used for fast-seeking vaccination strategies for emerging pathogens in the future.

Abstract Background Polyunsaturated fatty acid (PUFA) synthase is a multi-domain mega-enzyme that effectively synthesizes a series of PUFAs in marine microorganisms. The dehydratase (DH) domain of a PUFA synthase plays a crucial role in double bond positioning in fatty acids. Sequencing results of the coccolithophore Emiliania huxleyi (E. huxleyi, Eh) indicated that this species contains a PUFA synthase with multiple DH domains. Therefore, the current study, sought to define the functions of these DH domains (EhDHs), by cloning and overexpressing the genes encoding FabA-like EhDHs in Escherichia coli (E. coli) and Arabidopsis thaliana (A. thaliana). Results A complementation test showed that the two FabA-like DH domains could restore DH function in a temperature-sensitive (Ts) mutant. Meanwhile, overexpression of FabA-like EhDH1 and EhDH2 domains increased the production of unsaturated fatty acids (UFAs) in recombinant E. coli by 43.5–32.9%, respectively. Site-directed mutagenesis analysis confirmed the authenticity of active-site residues in these domains. Moreover, the expression of tandem EhDH1-DH2 in A. thaliana altered the fatty acids content, seed weight, and germination rate. Conclusions The two FabA-like DH domains in the E. huxleyi PUFA synthase function as 3-hydroxyacyl-acyl carrier protein dehydratase in E. coli. The expression of these domains in E. coli and A. thaliana can alter the fatty acid profile in E. coli and increase the seed lipid content and germination rate in A. thaliana. Hence, introduction of DH domains controlling the dehydration process of fatty acid biosynthesis in plants might offer a new strategy to increase oil production in oilseed plants.

Abstract Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects multiple systems and increases the risk of mental disorders such as depression and anxiety. We conducted an observational, single-center, cross-sectional study to investigate the relationship between depression, anxiety, and SLE disease activity. Methods The Patient Health Questionnaire 9 (PHQ-9) was used to assess depression, and the 7-item Generalized Anxiety Disorders Scale was used to assess anxiety (GAD-7). Using the chi-square/exact Fisher's tests, socio-demographic data, clinical and other characteristics of SLE patients were compared between depression or anxiety and non-depression/non-anxiety groups. To identify optimal levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) for predicting depression or anxiety, receiver-operator curves (ROC) were drawn. Results Among the 325 patients involved in this study, patients with depression or anxiety had significantly higher SLE activity (p

Abstract We aimed to establish a predictive model assessing perioperative blood transfusion risk using a nomogram. Clinical data for 97,443 surgery patients were abstracted from the DATADRYAD website; approximately 75% of these patients were enrolled in the derivation cohort, while approximately 25% were enrolled in the validation cohort. Multivariate logical regression was used to identify predictive factors for transfusion. Receiver operating characteristic (ROC) curves, calibration plots, and decision curves were used to assess the model performance. In total, 5888 patients received > 1 unit of red blood cells; the total transfusion rate was 6.04%. Eight variables including age, race, American Society of Anesthesiologists' Physical Status Classification (ASA-PS), grade of kidney disease, type of anaesthesia, priority of surgery, surgery risk, and an 18-level variable were included. The nomogram achieved good concordance indices of 0.870 and 0.865 in the derivation and validation cohorts, respectively. The Youden index identified an optimal cut-off predicted probability of 0.163 with a sensitivity of 0.821 and a specificity of 0.744. Decision curve (DCA) showed patients had a standardized net benefit in the range of a 5–60% likelihood of transfusion risk. In conclusion, a nomogram model was established to be used for risk stratification of patients undergoing surgery at risk for blood transfusion. The URLs of web calculators for our model are as follows: http://www.empowerstats.net/pmodel/?m=11633_transfusionpreiction .

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A–15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π–π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE−inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

BackgroundBlood transfusion is a frequent and necessary practice in acute type A aortic dissection (AAAD) patients, but the effect of plasma/red blood cells (RBCs) ratio on mortality remains unclear. The aim of this study is to investigate the association between plasma/RBCs transfusion ratio and in-hospital mortality in patients with AAAD.MethodsPatients were admitted to Xiangya Hospital of Central South University from January 1, 2016 to December 31, 2021. Clinical parameters were recorded. Multivariate Cox regression model was used to analyze the association between transfusion and in-hospital mortality. We used the smooth curve fitting and segmented regression model to assess the threshold effect between plasma/RBCs transfusion ratio and in-hospital mortality in patients with AAAD.ResultsThe volumes of RBCs [14.00 (10.12–20.50) unit] and plasma [19.25 (14.72–28.15) unit] transfused in non-survivors were significantly higher than in survivors [RBCs: 8.00 (5.50–12.00) unit]; plasma: [10.35 (6.50–15.22) unit]. Multivariate Cox regression analysis showed plasma transfusion was an independent risk factor of in-hospital mortality. Adjusted HR was 1.03 (95% CI: 0.96–1.11) for RBCs transfusion and 1.08 (95% CI: 1.03–1.13) for plasma transfusion. In the spline smoothing plot, mortality risk increased with plasma/RBCs transfusion ratio leveling up to the turning point 1. Optimal plasma/RBCs transfusion ratio with least mortality risk was 1. When the plasma/RBCs ratio was 1.5 (adjusted HR per 0.1 ratio: 1.09, 95% CI per 0.1 ratio:0.97–1.23), mortality risk tended to reach saturation, and increased non-significantly with the increase of ratio.ConclusionA 1:1 plasma/RBCs ratio was associated with the lowest mortality in the patients with AAAD. And non-linear relationship existed between plasma/RBCs ratio and mortality.

Insulin-like peptides (ILPs) are essential to the animal kingdom for regulating growth and development, reproduction, behavior, metabolism, and lifespan. In crustaceans, the most well-known ILP is insulin-like androgenic gland hormone, a key hormone in regulating sex differentiation and reproduction. Identification of other ILPs and their functions are still limited. In this study, an insulin-like peptide gene of the swimming crab Portunus trituberculatus was cloned and characterized. Its transcripts were mainly found in nerve tissues and expression could be induced by glucose, implying a putative role in glucoregulation. After depletion of endogenous ILP, injection of ILP dsRNA (dsILP) significantly elevated blood glucose levels and recombinant ILP (rILP) decreased hemolymph glucose levels, further clarifying the involvement of acquired ILP in hemolymph glucose regulation. Injection of dsILP decreased PtAkt, PtGS, PtPFK and increased PtGSK and PtPEPCK gene expression. The opposite profile was observed after glucose and rILP injection, indicating that PtILP might negatively regulate hemolymph glucose levels via the IIS (insulin/IGF-1 signaling) pathway by inhibiting gluconeogenesis and promoting glycogen synthesis and glycolysis. This study has refined the mechanism of glucose regulation in crustaceans and laid the foundation for further studies on ILP function.

Abstract Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of “Semi-implantable bioelectronics”, summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.

Abstract Tumor killing and wound healing are two complementary and influential processes during the treatment of melanoma. Herein, a two-layered microneedle platform was developed with bifunctional effect of chemo-photothermal synergistic melanoma therapy and skin regeneration. The bifunctional platform composed of embeddable curcumin nanodrugs/new Indocyanine Green/hyaluronic acid (Cur NDs/IR820/HA) microneedles and sodium alginate/gelatin/hyaluronic acid (SA/Ge/HA) supporting backing layer was prepared through a two-step casting process. With uniform incorporation of curcumin nanodrugs and IR820, the microneedles exhibited excellent photothermal performance under external near-infrared (NIR) light stimulation and tumor co-therapy ability. Once the embeddable microneedles were inserted into skin, they would rapidly dissolve and activate drug release successfully for tumor treatment. Moreover, the SA/Ge/HA supporting backing layer was left behind to cover the wound and promote the proliferation of endothelial and fibroblasts cells for enhanced skin regeneration. The two-layered microneedles platform can simultaneously eliminate the tumor and accelerate wounding healing, which may be potentially employed as a competitive strategy for the treatment of melanoma. Graphical Abstract

Towards intelligent treatment for glaucoma, here authors demonstrate integrated wireless theranostic contact lenses for in situ electrical sensing of intraocular pressure and on demand anti-glaucoma drug delivery.

Abstract Background Producing large amounts of soluble proteins from bacteria remains a challenge, despite the help of current various solubilizing fusion tags. Thus, developing novel tags is necessary. Antifreeze protein (AFP) has excellent solubility and hydrophilicity, but there are no current reports on its use as a solubilizing fusion tag. Additionally, there is no precedent for using retro-proteins (reverse sequence) as solubilizing fusion tags. Therefore, we selected the antifreeze protein AXX and obtained its retro-protein XXA by synthesizing the XXA gene for the development of a new solubilizing fusion tag. Results XXA exhibits better stability and ease of expression than AXX; hence, we focused the development of the solubilizing fusion tag on XXA. XXA fused with the tested inclusion bodies, significantly increasing the soluble expression compared with commonly used solubilizing fusion tags such as GST, Trx, Sumo, MBP, and NusA. The tested proteins became soluble after fusion with the XXA tag, and they could be purified. They maintained a soluble form after XXA tag removal. Finally, we used enzymatic digestion reaction and western blot experiments to verify that bdNEDP1 and NbALFA, which were soluble expressed by fusion with XXA, were active. Conclusion We developed the novel solubilizing fusion tag XXA, which could more effectively facilitate the soluble expression of inclusion bodies compared with current commonly used tags. XXA could function at both low and high temperatures, and its moderate molecular weight has a limited impact on the output. These properties make XXA an ideal fusion tag for future research and industrial production. Moreover, for the first time, we highlighted the broad potential of antifreeze protein as a solubilizing fusion tag, bringing retro-protein into practical application.

Abstract Background Effective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity assays can effectively aid clinical decision-making and intervene in cancer in a localized status before they metastasize and become unmanageable. Meanwhile, it is equally pivotal to prevent overdiagnosis of non-life-threatening cancer by eliminating unnecessary treatment and repeated blood draws. Unfortunately, current clinical screening methodologies can hardly simultaneously attain sufficient sensitivity and specificity, especially under resource-restrained circumstances. To circumvent such limitations, particularly for cancer biomarkers from early-onset and recurrence, we aim to develop a universal plasmonic platform for clinical applications, which macroscopically amplifies multiplexed fluorescence signals in a broad spectral window and readily adapts to current assay setups without sophisticated accessories or expertise at low cost. Methods The plasmonic substrate was chemically synthesized in situ at the solid–liquid interface by rationally screening a panel of reducing monosaccharides and tuning the redox reactions at various catalyst densities and precursor concentrations. The redox properties were studied by Benedict’s assay and electrochemistry. We systemically characterized the morphologies and optical properties of the engineered plasmonic Ag structures by scanning electron microscopy (SEM) and spectroscopy. The structure-fluorescence enhancement correlation was explicitly explained by the finite-difference time-domain (FDTD) simulation and a computational model for gap distribution. Next, we established an enhanced fluoroimmunoassay (eFIA) using a model biomarker for prostate cancer (PCa) and validated it in healthy and PCa cohorts. Prognosis was explored in patients subject to surgical and hormonal interventions following recommended PCa guidelines. Results The monosaccharide-mediated redox reaction yielded a broad category of Ag structures, including sparsely dispersed nanoparticles (NPs) of various sizes, semi-continuous nanoislands, and crackless continuous films. Optimal broad-spectral fluorescence enhancement from green to far-red was observed for the inhomogeneous, irregularly-shaped semi-continuous Ag nanoisland substrate (AgNIS), synthesized from a well-balanced redox reaction at a stable rate mediated by mannose. In addition, different local electric field intensity distributions in response to various incident excitations were observed at the nanoscale, elucidating the need for irregular and inhomogeneous structures. AgNIS enabled a maximized 54.7-fold macroscopically amplified fluorescence and long-lasting photostability. Point-of-care availability was fulfilled using a customized smartphone prototype with well-paired optics. The eFIA effectively detected the PCa marker in cell lines, xenograft tumors, and patient sera. The plasmonic platform rendered a diagnostic sensitivity of 86.0% and a specificity of 94.7% and capably staged high-grade PCa that the clinical gold standard test failed to stratify. Patient prognosis of robotic-assisted surgeries and hormone therapies was non-invasively monitored following efficient medical interventions. The assay time was significantly curtailed on the plasmonic platform upon microwave irradiation. Conclusions By investigating the effects of reducing monosaccharides on the seed-mediated chemical synthesis of plasmonic Ag structures, we deduced that potent multiplexed fluorescence enhancement originated from both an adequate reducing power and a steady reduction rate. Furthermore, the inhomogeneous structure with adequate medium gap distances afforded optimal multiwavelength fluorescence enhancement, thus empowering an effective eFIA for PCa. The clinically validated diagnostic and prognostic features, along with the low sample volume, point-of-care feasibility with a smartphone, and microwave-shortened assay time, warrant its potential clinical translation for widespread cancer biomarker analysis. Graphical Abstract

Abstract With the advent of the 5G era and the rise of the Internet of Things, various sensors have received unprecedented attention, especially wearable and stretchable sensors in the healthcare field. Here, a stretchable, self-healable, self-adhesive, and room-temperature oxygen sensor with excellent repeatability, a full concentration detection range (0-100%), low theoretical limit of detection (5.7 ppm), high sensitivity (0.2%/ppm), good linearity, excellent temperature, and humidity tolerances is fabricated by using polyacrylamide-chitosan (PAM-CS) double network (DN) organohydrogel as a novel transducing material. The PAM-CS DN organohydrogel is transformed from the PAM-CS composite hydrogel using a facile soaking and solvent replacement strategy. Compared with the pristine hydrogel, the DN organohydrogel displays greatly enhanced mechanical strength, moisture retention, freezing resistance, and sensitivity to oxygen. Notably, applying the tensile strain improves both the sensitivity and response speed of the organohydrogel-based oxygen sensor. Furthermore, the response to the same concentration of oxygen before and after self-healing is basically the same. Importantly, we propose an electrochemical reaction mechanism to explain the positive current shift of the oxygen sensor and corroborate this sensing mechanism through rationally designed experiments. The organohydrogel oxygen sensor is used to monitor human respiration in real-time, verifying the feasibility of its practical application. This work provides ideas for fabricating more stretchable, self-healable, self-adhesive, and high-performance gas sensors using ion-conducting organohydrogels.

Abstract Stretchable hydrogel‐based strain sensors suffer from limited sensitivity, which urgently requires further breakthroughs for precise and stable human‐computer interaction. Here, an efficient microstructural engineering strategy is proposed to significantly enhance the sensitivity of hydrogel‐based strain sensors by sandwiching an emulsion‐polymerized polyacrylamide organohydrogel microsphere membrane between two Ecoflex films, which are accompanied by crack generation and propagation effects upon stretching. Consequently, the as‐developed strain sensor exhibits ultrahigh sensitivity (gauge factor (GF) of 1275), wide detection range (100% strain), low hysteresis, ultralow detection limit (0.05% strain), good fatigue resistance, and low fabrication cost. In addition, the sensor features good water, dehydration, and frost resistance, enabling real‐time strain monitoring in various complex conditions due to the encapsulation of Ecoflex film and the addition of glycerol and KCl. Through further structural manipulation, the device achieves superior response to tiny strains, with a GF value of 98.3 in the strain range of less than 1.5%. Owing to the high strain sensing performance, the sensor is able to detect various human activities from swallowing to finger bending even under water. On this basis, a wireless sensing system with apnea warning and single‐channel gesture recognition capabilities is successfully demonstrated, demonstrating its great promise as wearable electronics.

Abstract To date, development of high‐performance, stretchable gas sensors operating at and below room temperature (RT) remains a challenge in terms of traditional sensing materials. Herein, we report on a high‐performance NO2 gas sensor based on a self‐healable, recyclable, ultrastretchable, and stable polyvinyl alcohol–cellulose nanofibril double‐network organohydrogel, which features ultrahigh sensitivity (372%/ppm), low limit of detection (2.23 ppb), relatively fast response and recovery time (41/144 s for 250 ppb NO2), good selectivity against interfering gases (NH3, CO2, ethanol, and acetone), excellent reversibility, repeatability, and long‐term stability at RT or even at −20°C. In particular, this sensor shows outstanding stability against large deformations and mechanical damages so that it works normally after rapid self‐healing or remolding after undergoing mechanical damage without significant performance degradation, which has major advantages compared to state‐of‐the‐art gas sensors. The high NO2 sensitivity and selectivity are attributed to the selective redox reactions at the three‐phase interface of gas, gel, and electrode, which is even boosted by applying tensile strain. With a specific electrical circuit design, a wireless NO2 alarm system based on this sensor is created to enable continuous, real‐time, and wireless NO2 detection to avoid the risk of exposure to NO2 higher than threshold concentrations.

Abstract Background The platelet-lymphocyte ratio (PLR), a novel inflammatory marker, is generally associated with increased in-hospital mortality risk. We aimed to investigate the association between PLR and postoperative in-hospital mortality risk in patients with type A acute aortic dissection (AAAD). Methods Patients (n = 270) who underwent emergency surgery for AAAD at Xiangya Hospital of Central South University between January 2014 and May 2019 were divided into three PLR-based tertiles. We used multiple regression analyses to evaluate the independent effect of PLR on in-hospital mortality, and smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between PLR and in-hospital mortality risk. Results The overall postoperative in-hospital mortality was 13.33%. After adjusting for confounders, in-hospital mortality risk in the medium PLR tertile was the lowest (Odds ratio [OR] = 0.20, 95% confidence interval [CI] = 0.06–0.66). We observed a U-shaped relationship between PLR and in-hospital mortality risk after smoothing spline fitting was applied. When PLR 188, the in-hospital mortality risk increased by 6% per unit increase in PLR (OR = 1.06, P = 0.045). Conclusions There was a U-shaped relationship between PLR and in-hospital mortality in patients with AAAD, with an optimal PLR range for the lowest in-hospital mortality risk of 108–188. PLR may be a useful preoperative prognostic tool for predicting in-hospital mortality risk in patients with AAAD and can ensure risk stratification and early treatment initiation.

Abstract We present green organohydrogel‐based stretchable (up to 700% strain), transparent, and room‐temperature O2 sensors with impressive performance, including drying and freezing tolerances, high sensitivity, broad detection range (100 ppm‐100%), long‐term stability, low theoretical detection limit (0.585 ppm), linearity, and the capability to real‐time monitor human respiration by directly attaching on human skin. A facile solvent replacement approach is employed to partially exchange water with natural and edible xylitol/sorbitol molecules, generating stable, green and tough organohydrogels. Compared with the pristine hydrogel counterpart, the organohydrogel‐based O2 sensors feature higher stability, prolonged life time (140 days) and the ability to work over a wide range of temperatures (−38 to 65°C). The O2 sensing mechanism is elucidated by investigating the redox reactions occurred at the electrode‐hydrogel interface. This work develops a facile strategy to fabricate stretchable, transparent, and high‐performance O2 sensor using stable and green organohydrogels as novel transducing materials for practical wearable applications.

Abstract Corneal injury can lead to severe vision impairment or even blindness. Although numerous methods are developed to accelerate corneal wound healing, most of them are passive treatments that rarely participate in controlling endogenous cell behaviors or are incompatible with nontransparent bandage. In this work, a wireless‐powered electrical bandage contact lens (EBCL) is developed to generate a localized external electric field to accelerate corneal wound healing and vision recovery. The wireless electrical stimulation circuit employed a flower‐shaped layout design that can be compactly integrated on bandage contact lens without blocking the vision. The role of the external electric field in promoting corneal wound healing is examined in vitro, where the responses of directional migration and corneal cells alignment to the electric field are observed. The RNA sequencing (RNA‐seq) analysis indicates that the electrical stimulation can participate in controlling cell division, proliferation, and migration. Furthermore, the wireless EBCL is demonstrated to accelerate the completed recovery of corneal wounds on rabbits’ eyes by electrical stimulation, while the control group exhibits delayed recovery and obvious corneal defects. As a new generation of intelligent device, the wireless and patient‐friendly EBCL can provide a promising therapeutic strategy for ocular diseases.