Identification Analysis of Angelicae sinensis radix and Angelicae pubescentis radix Based on Quantized "Digital Identity" and UHPLC-QTOF-MSE Analysis.

Angelicae sinensis radix (ASR) and Angelicae pubescentis radix (APR), as traditional herbal medicines, are often confused and doped in the material market. However, the traditional identification method is to characterize the whole herb with a single or a few components, which do not have representation and cannot realize the effective utilization of unknown components. Consequently, the result is not convincing. In addition, the whole process is time-consuming and labor-intensive. To avoid the confusion and adulteration of ASR and APR as well as to strengthen quality control and improve identification efficiency, in this study, a UHPLC-QTOF-MSE method was used to analyze ASR and APR. Based on digital representation, the shared data with high ionic strength were extracted from different batches of the same herbal medicine as their "digital identity". Further, the above "digital identity" was used as the benchmark for matching and identifying unknown samples to feedback on matching credibility (MC). The results showed that based on the "digital identities" of ASR and APR, the digital identification of two herbal samples can be realized efficiently and accurately at the individual level. And the matching credibility (MC) was higher than 94.00%, even if only 1% of APR or ASR in the mixed samples can still be identified efficiently and accurately. The study is of great practical significance for improving the efficiency of the identification of ASR and APR, cracking down on adulterated and counterfeit drugs, and strengthening the quality control of ASR and APR. In addition, it has important reference significance for developing nontargeted digital identification of herbal medicines at the individual level based on UHPLC-QTOF-MSE and "digital identity", which is beneficial to the construction of digital Chinese medicine and digital quality control.

Nanomaterials revolutionize biosensing: 0D-3D designs for ultrasensitive detection of microorganisms and viruses.

Various diseases caused by harmful microorganisms and viruses have caused serious harm and huge economic losses to society. Thus, rapid detection of harmful microorganisms and viruses is necessary for disease prevention and treatment. Nanomaterials have unique properties that other materials do not possess, such as a small size effect and quantum size effect. Introducing nanomaterials into biosensors improves the performance of biosensors for faster and more accurate detection of microorganisms and viruses. This review aims to introduce the different kinds of biosensors and the latest advances in the application of nanomaterials in biosensors. In particular, this review focuses on describing the physicochemical properties of zero-, one-, two-, and three-dimensional nanostructures as well as nanoenzymes. Finally, this review discusses the applications of nanobiosensors in the detection of microorganisms and viruses and the future directions of nanobiosensors.

Polygonati Rhizoma varieties and origins traceability based on multivariate data fusion combined with an artificial intelligence classification algorithm.

This study collected multidimensional feature data such as spectra, texture, and component contents of Polygonati Rhizoma from different origins and varieties (Polygonatum kingianum Coll. et Hemsl from Yunnan and Guizhou; Polygonatum cyrtonema Hua from Anhui and Jiangxi; Polygonatum sibiricum Red from Hunan). Multivariate statistical analysis was used to select 39 characteristic factors for distinguishing PR origins and 14 characteristic factors for discriminating PR varieties (VIP > 1 and P < 0.05). In addition, by combining multivariate statistical analysis with a deep belief network (DBN) classification algorithm, a novel artificial intelligence algorithm was developed and optimized. Compared to traditional discriminant analysis methods, the accuracy of this new approach was significantly improved, achieving a 100% discrimination rate for PR varieties and a 100% accuracy rate for tracing the origin of PR. This research provides a reference and data support for constructing intelligent algorithms based on multidimensional data fusion, to achieve food variety discrimination and origin tracing.

Both Short-term and Long-term Ozone Pollution Alters the Chemical Composition of rice Grain.

The increasing ground-level ozone (O3) is threatening food security, especially in Asian areas, where rice is one of the most important staple crops. O3 impacts on rice could be exacerbated by its spatiotemporal heterogeneity. To improve evaluation accuracy and develop effective adaptations, direct data is urgently needed. Studies on the short-term effects of O3 on rice grain, however, are lacking. Which may lead to an underestimation of the O3 impacts. Through a field experiment, we studied the responses of grain nitrogen, grain carbon, and grain protein in rice cultivars to elevated concentrations of O3 (40 ppb plus that in background air, eO3), especially examining the effects of short-term eO3 during different plant growth stages. We found that long-term eO3 increased grain nitrogen by 29.29% in a sensitive rice cultivar, and short-term eO3 at the tillering and jointing stages increased grain nitrogen by 19.31%, and the grain carbon to nitrogen ratio was decreased by 14.70%, and 21.14% by short-term and long-term eO3. Here we demonstrate that short-term eO3 may significantly affect the chemical composition of rice grains. Previous evaluations of the effects of eO3 may be underestimated. Moreover, changes in the grain nitrogen and grain protein were greater when the short-term eO3 was added to rice plants during the tillering and jointing stage, compared to heading and ripening stage. These results suggest that to improve the tolerance of rice to eO3 to achieve food security, studies on cultivar screening, as well as developing growth-stage-specific adaptations are needed in future.

Pancreatic cancer cells hijack tumor suppressive microRNA-26a to promote radioresistance and potentiate tumor repopulation.

Pancreatic cancer is one of the most lethal cancers with significant radioresistance and tumor repopulation after radiotherapy. As a type of short non-coding RNA that regulate various biological and pathological processes, miRNAs might play vital role in radioresistance. We found by miRNA sequencing that microRNA-26a (miR-26a) was upregulated in pancreatic cancer cells after radiation, and returned to normal state after a certain time. miR-26a was defined as a tumor suppressive miRNA by conventional tumor biology experiments. However, transient upregulation of miR-26a after radiation significantly promoted radioresistance, while stable overexpression inhibited radioresistance, highlighting the importance of molecular dynamic changes after treatment. Mechanically, transient upregulation of miR-26a promoted cell cycle arrest and DNA damage repair to promote radioresistance. Further experiments confirmed HMGA2 as the direct functional target, which is an oncogene but enhances radiosensitivity. Moreover, PTGS2 was also the target of miR-26a, which might potentiate tumor repopulation via delaying the synthesis of PGE2. Overall, this study revealed that transient upregulation of miR-26a after radiation promoted radioresistance and potentiated tumor repopulation, highlighting the importance of dynamic changes of molecules upon radiotherapy.

Causal effect between gut microbiota and metabolic syndrome in European population: a bidirectional mendelian randomization study.

BACKGROUND: Observational studies have reported that gut microbiota composition is associated with metabolic syndrome. However, the causal effect of gut microbiota on metabolic syndrome has yet to be confirmed. METHODS: We performed a bidirectional Mendelian randomization study to investigate the causal effect between gut microbiota and metabolic syndrome in European population. Summary statistics of gut microbiota were from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium. The summary statistics of outcome were obtained from the most comprehensive genome-wide association studies of metabolic syndrome (n = 291,107). The inverse-variance weighted method was applied as the primary method, and the robustness of the results was assessed by a series of sensitivity analyses. RESULTS: In the primary causal estimates, Actinobacteria (OR = 0.935, 95% CI = 0.878-0.996, P = 0.037), Bifidobacteriales (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Bifidobacteriaceae (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Desulfovibrio (OR = 0.920, 95% CI = 0.869-0.975, P = 0.005), and RuminococcaceaeUCG010 (OR = 0.882, 95% CI = 0.803-0.969, P = 0.009) may be associated with a lower risk of metabolic syndrome, while Lachnospiraceae (OR = 1.130, 95% CI = 1.016-1.257, P = 0.025), Veillonellaceae (OR = 1.055, 95% CI = 1.004-1.108, P = 0.034) and Olsenella (OR = 1.046, 95% CI = 1.009-1.085, P = 0.015) may be linked to a higher risk for metabolic syndrome. Reverse MR analysis demonstrated that abundance of RuminococcaceaeUCG010 (OR = 0.938, 95% CI = 0.886-0.994, P = 0.030) may be downregulated by metabolic syndrome. Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy. CONCLUSIONS: Our Mendelian randomization study provided causal relationship between specific gut microbiota and metabolic syndrome, which might provide new insights into the potential pathogenic mechanisms of gut microbiota in metabolic syndrome and the assignment of effective therapeutic strategies.

Disulfidptosis in head and neck squamous carcinoma: Integrative bioinformatic and in-vitro analysis.

BACKGROUND: Head and neck squamous carcinoma (HNSC) is a prevalent global malignancy with limited treatment options, which necessitates the development of novel therapeutic strategies. Disulfidptosis, a recently discovered and unique cell death pathway, may offer promise as a treatment target in HNSC. MATERIALS AND METHODS: We identified disulfidptosis-related genes (DRGs) using multiple algorithms and developed a prognostic model based on a disulfidptosis-related gene index (DRGI). The model's predictive accuracy was assessed by ROC-AUC, and patients were stratified by risk scores. We investigated the tumor immune microenvironment, immune responses, tumorigenesis pathways, and chemotherapy sensitivity (IC50). We also constructed a diagnostic model using 20 machine-learning algorithms and validated PCBP2 expression through RT-qPCR and western blot. RESULTS: We developed a 12-DRG DRGI prognostic model, classifying patients into high- and low-risk groups, with the high-risk group experiencing poorer clinical outcomes. Notable differences in tumor immune microenvironment and chemosensitivity were observed, with reduced immune activity and suboptimal treatment responses in the high-risk group. Advanced machine learning and in-vitro experiments supported DRGI's potential as a reliable HNSC diagnostic biomarker. CONCLUSION: We established a novel DRGI-based prognostic and diagnostic model for HNSC, exploring its tumor immune microenvironment implications, and offering valuable insights for future research and clinical trials.

F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/ß-Catenin pathway.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. METHODS: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. RESULTS: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein ß-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate ß-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. CONCLUSION: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/ß-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

3D-printed, citrate-based bioresorbable vascular scaffolds for coronary artery angioplasty.

Fully bioresorbable vascular scaffolds (BVSs) aim to overcome the limitations of metallic drug-eluting stents (DESs). However, polymer-based BVSs, such as Abbott's Absorb, the only US FDA-approved BVS, have had limited use due to increased strut thickness (157 µm for Absorb), exacerbated tissue inflammation, and increased risk of major cardiac events leading to inferior clinical performance when compared to metallic DESs. Herein we report the development of a drug-eluting BVS (DE-BVS) through the innovative use of a photopolymerizable, citrate-based biomaterial and a high-precision additive manufacturing process. BVS with a clinically relevant strut thickness of 62 µm can be produced in a high-throughput manner, i.e. one BVS per minute, and controlled release of the anti-restenosis drug everolimus can be achieved by engineering the structure of polymer coatings to fabricate drug-eluting BVS. We achieved the successful deployment of BVSs and DE-BVSs in swine coronary arteries using a custom-built balloon catheter and BVS delivery system and confirmed BVS safety and efficacy regarding maintenance of vessel patency for 28 days, observing an inflammation profile for BVS and DE-BVS that was comparable to the commercial XIENCE™ DES (Abbott Vascular).

Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects.

Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8+ T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

SCPL acyltransferases catalyze the metabolism of chlorogenic acid during purple coneflower seed germination.

The metabolism of massively accumulated chlorogenic acid is crucial for the successful germination of purple coneflower (Echinacea purpurea (L.) Menoch). A serine carboxypeptidase-like (SCPL) acyltransferase (chicoric acid synthase, CAS) utilizes chlorogenic acid to produce chicoric acid during germination. However, it seems that the generation of chicoric acid lags behind the decrease in chlorogenic acid, suggesting an earlier route of chlorogenic acid metabolism. We discovered another chlorogenic acid metabolic product, 3,5-dicaffeoylquinic acid, which is produced before chicoric acid, filling the lag phase. Then, we identified two additional typical clade IA SCPL acyltransferases, named chlorogenic acid condensing enzymes (CCEs), that catalyze the biosynthesis of 3,5-dicaffeoylquinic acid from chlorogenic acid with different kinetic characteristics. Chlorogenic acid inhibits radicle elongation in a dose-dependent manner, explaining the potential biological role of SCPL acyltransferases-mediated continuous chlorogenic acid metabolism during germination. Both CCE1 and CCE2 are highly conserved among Echinacea species, supporting the observed metabolism of chlorogenic acid to 3,5-dicaffeoylquinic acid in two Echinacea species without chicoric acid accumulation. The discovery of SCPL acyltransferase involved in the biosynthesis of 3,5-dicaffeoylquinic acid suggests convergent evolution. Our research clarifies the metabolism strategy of chlorogenic acid in Echinacea species and provides more insight into plant metabolism.

EpMYB2 positively regulates chicoric acid biosynthesis by activating both primary and specialized metabolic genes in purple coneflower.

Chicoric acid is the major active ingredient of the world-popular medicinal plant purple coneflower (Echinacea purpurea (L.) Menoch). It is recognized as the quality index of commercial hot-selling Echinacea products. While the biosynthetic pathway of chicoric acid in purple coneflower has been elucidated recently, its regulatory network remains elusive. Through co-expression and phylogenetic analysis, we found EpMYB2, a typical R2R3-type MYB transcription factor (TF) responsive to methyl jasmonate (MeJA) simulation, is a positive regulator of chicoric acid biosynthesis. In addition to directly regulating chicoric acid biosynthetic genes, EpMYB2 positively regulates genes of the upstream shikimate pathway. We also found that EpMYC2 could activate the expression of EpMYB2 by binding to its G-box site, and the EpMYC2-EpMYB2 module is involved in the MeJA-induced chicoric acid biosynthesis. Overall, we identified an MYB TF that positively regulates the biosynthesis of chicoric acid by activating both primary and specialized metabolic genes. EpMYB2 links the gap between the JA signaling pathway and chicoric acid biosynthesis. This work opens a new direction toward engineering purple coneflower with higher medicinal qualities.

Chinese consumer preference for beef with geographical indications and other attributes.

As the demand for beef products grows in the Chinese market, understanding consumer preferences for beef, especially those related to quality labelling, is essential. The recent agreement between China and the European Union to promote Geographical Indications (GIs) provides a new insight into preferences for beef with quality labelling. This paper assesses consumer preferences for beef products with GIs and other attributes. A nationwide survey is conducted including 1210 respondents in China by a choice experiment attributing GI label, 'green', 'hazard-free', and 'organic' labels, feeding regimes (grain-fed, grass-fed), country of origin (China, Ireland, Australia, Brazil), and price (30, 40, 80, 100 ¥/500 g). The random parameter logit model with error component reveals that Chinese consumers have a significant preference for grain-fed beef and domestic beef, and they are willing to pay a premium price for GI-labelled beef compared with other attributes. The interaction between GIs and country of origin is included to indicate the positive price impact of GIs on imported beef products. Demographic factors such as place of residence and occupation are found to affect consumer preferences for GIs.

Bidirectional effect of uric acid on C2C12 myotubes and its partial mechanism.

AIM: To explore the effects and mechanisms of different concentrations of uric acid on skeletal muscle cells. METHODS: C2C12 myoblasts were differentiated into myotubes and then exposed to a medium containing uric acid (0 µM, 200 µM, 400 µM, 600 µM, 800 µM, 1000 µM, 1200 µM, 1400 µM). The myotube diameters were observed under light microscopy; the expressions of myosin heavy chain (MyHC), autophagy-related proteins (LC3BII/LC3BI, P62), cGAS, and p-Sting/Sting proteins were analyzed using Western blotting or immunoprecipitation; and oxidative stress and mitochondrial damage were evaluated using ROS, mtDNA and JC-1 assays. Cell viability was measured via CCK8 assay, and 1000-µM uric acid was selected for follow-up experiments. Furthermore, C2C12 myotubes were divided into a blank control group (Ctrl), a high-uric-acid group (HUA), and an HUA plus cGASn inhibitor group (HUA + RU.521). Then, the myotube diameter was observed, oxidative stress and mitochondrial damage were evaluated, and MyHC and autophagy-related protein expressions were analysed. RESULTS: C2C12 myotubes cultured in 400-µM uric acid medium had the greatest myotube diameter and the highest MyHC protein expression. At 1000-µM uric acid, the diameter and MyHC protein expression were significantly decreased, LCB3II/LCB3I expression was notably increased, and the level of p62 protein expression was considerably decreased. RU.521 partially alleviated the HUA-induced C2C12 myotubes changes. CONCLUSIONS: Uric acid bidirectionally affected C2C12 myotubes: 400-µΜ uric acid promoted myotube growth, while 1000-µΜ uric acid triggered myotube atrophy with increased autophagy. Inhibiting cGAS-Sting signaling attenuated HUA-induced C2C12 myotube autophagy and atrophy. Geriatr Gerontol Int 2024; 24: 430-439.

Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD-1 blockade.

The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.

Association between RMTg Neuropeptide Genes and Negative Effect during Alcohol Withdrawal in Mice.

Alcohol use disorders (AUDs) frequently co-occur with negative mood disorders, such as anxiety and depression, exacerbating relapse through dopaminergic dysfunction. Stress-related neuropeptides play a crucial role in AUD pathophysiology by modulating dopamine (DA) function. The rostromedial tegmental nucleus (RMTg), which inhibits midbrain dopamine neurons and signals aversion, has been shown to increase ethanol consumption and negative emotional states during abstinence. Despite some stress-related neuropeptides acting through the RMTg to affect addiction behaviors, their specific roles in alcohol-induced contexts remain underexplored. This study utilized an intermittent voluntary drinking model in mice to induce negative effect behavior 24 h into ethanol (EtOH) abstinence (post-EtOH). It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors. We observed that adult male C57BL/6J mice displayed evident anxiety, anhedonia, and depression-like symptoms at 24 h post-EtOH. The laser-capture microdissection technique, coupled with or without retrograde tracing, was used to harvest total ventral tegmental area (VTA)-projecting neurons or the intact RMTg area. The findings revealed that post-EtOH consistently reduced Pnoc and Orx levels while elevating Crf levels in these neuronal populations. Notably, RMTg Pnoc and Npy levels counteracted ethanol consumption and depression severity, while Crf levels were indicative of the mice's anxiety levels. Together, these results underscore the potential role of stress-related neuropeptides in the RMTg in regulating the negative emotions related to AUDs, offering novel insights for future research.

A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis.

OBJECTIVES: Growing evidence appears to intimate a profound connection between periodontitis and coronary atherosclerosis (CA), yet the existence of a causal relationship remains unclear. Through the implementation of Mendelian randomization analysis, we further evaluated the potential causal link between chronic/acute periodontitis (CP/AP) and CA. METHODS: Utilizing genome-wide association study (GWAS) summary statistics, we incorporated periodontitis data derived from European samples (n1 = 198,441; n2 = 195,762) and CA data from 61,194 cases. We conducted a 2 sample, bidirectional Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the main analytical approach. Supplementary analyses were executed through MR Egger, Weighted median (WM), IVW, Simple mode, and Weighted mode approaches. RESULTS: The IVW analysis revealed no significant causal relationship between CA and periodontitis (CA-CP: OR = 2.110, 95% CI = 0.208-21.317, P = .527; CA-AP: OR = 0.414, 95% CI = 0.051-3.384, P = .644). Similarly, the bidirectional analysis did not identify impact of periodontitis on CA (OR = 1.000, 95% CI = 0.999-1.001, P = .953). The supplementary analyses corroborated these findings. CONCLUSIONS: While studies highlighting a correlation between periodontitis and CA, our comprehensive analysis does not corroborate a causal association between periodontitis and CA. Further research is needed to elucidate other potential shared mechanisms and causal evidence between periodontitis and CA.

MnO2-based dual channel surface plasmon resonance fiber sensor for trace glutathione and refractive index detection.

Glutathione (GSH) plays vital role in human biological systems, so its rapid and sensitive detection is necessary for health condition monitoring. In this work, a simple structure for dual channel GSH and refractive index (RI) detection is proposed. By introducing Au-MnO2 thin film coating on the fiber surface for the first time, GSH solution would lead to the dissolution of MnO2, the change in GSH levels could be monitored over a short period in channel 2. For channel 1, ITO-Ag thin film is applied for RI change detection. After optimization, the GSH detection sensitivity reached about -2.361 nm/mM in the range of 0.005-50 mM, and the RI sensitivity reached 1704.252 nm/RIU in the range of 1.331-1.3895 RIU. Channel 1 could also put into GSH detection in the high concentration scale to enlarge the sensor's range and 0.095 nm/mM of sensitivity is acquired within the range of 50-600 mM. With the presence of MnO2 film, the detection sensitivity increased 25.663 times. Neither channel interferes with the operation of the other. Proposed sensor provides stability, high selectivity and elevation in GSH detection sensitivity, which shows great potential for environmental and biological detection field and their applications.

Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels.

BACKGROUND & AIMS: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. METHODS: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. RESULTS: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. CONCLUSIONS: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. IMPACT AND IMPLICATIONS: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.