Ordered assembly of two different metal clusters with the same topological connectivity in one single coordination network.

The introduction of heterogeneous components within one single coordination network leads to the multifunctionality of the final material. However, it is hard to precisely control the local distribution of these different components in such a coordination network, especially for different components with identical topological connectivity. In this study, we successfully achieved the ordered assembly of [Mn3(µ3-O)] nodes and [Mn6(µ3-O)2(CH3COO)3] nodes within one pacs coordination network. The resulting new structure (NPU-6) with heterogeneous metal nodes simultaneously inherits the advantages of both parent networks (good thermal stability and high pore volume). The significant effect of the reaction concentration of competing ligand CH3COO- on the mixed assembly of these two nodes in NPU-6 is revealed by a series of control experiments. This method is anticipated to offer a valuable reference for orderly assembling heterogeneous components in coordination networks.

[Analysis of risk factors for postoperative delirium in elderly patients undergoing spinal surgery].

OBJECTIVE: To investigate the risk factors of postoperative delirium in elderly patients undergoing spine surgery. METHODS: The basic case data of 566 patients who underwent spine surgery under general anesthesia from January 2021 to January 2023 were retrospectively analyzed. There were 296 males and 270 females with an average age of (71.58 ± 4.21) years old. There were 195 cases of cervical spine surgery, 26 cases of thoracic spine surgery and 345 cases of lumbar spine surgery.According to the occurrence of postoperative delirium, the patients were divided into postoperative delirium group(41 patients) and non-delirium group (525 patients). Univariate analysis was used to analyze the possible influencing factors such as gender, age, weight, smoking history, drinking history, surgical site, preoperative anxiety, intraoperative hypotension times, blood loss and so on, and binary Logistic regression was used to analyze the univariate factors with P<0.05. RESULTS: A total of 41 patients developed postoperative delirium. Univariate analysis showed that age (P=0.000), duration of surgery (P=0.039), preoperative anxiety (P=0.001), blood loss (P=0.000), history of opioid use (P=0.003), history of stroke (P=0.005), C-reactive protein (P=0.000), sodium ion(P=0.000) were significantly different between delirium group and non-delirium group. These factors were included in the binary Logistic regression analysis, and the results showed that age [OR=0.729, 95%CI(0.569, 0.932), P=0.012], opioid use [OR=21.500, 95%CI(1.334, 346.508), P=0.031], blood loss [OR=0.932, 95%CI(0.875, 0.993), P=0.029], C-reactive protein [OR=0.657, 95%CI(0.485, 0.890), P=0.007], preoperative anxiety [OR=23.143, 95%CI(1.859, 288.090), P=0.015], and sodium [OR=1.228, 95%CI(1.032, 1.461), P=0.020] were independent risk factors for the development of delirium after spinal surgery in elderly patients. CONCLUSION: Age, opioid use, blood loss, preoperative anxiety, elevated c-reactive protein, and hyponatremia are independent risk factors for the development of postoperative delirium in elderly patients undergoing spinal surgery.

An ultrastable 1397-nm laser stabilized by a crystalline-coated room-temperature cavity.

State-of-the-art optical cavities are pivotal in pushing the envelope of laser frequency stability below 10-16. This is often achieved by extending the cavity length or cooling the system to cryogenic temperatures to reduce the thermal noise floor. In our study, we present a 30-cm-long cavity that operates at room temperature and is outfitted with crystalline coatings. The system has a predicted ultralow thermal noise floor of 4.4 × 10-17, comparable to what is observed in cryogenic silicon cavities. A 1397-nm laser is stabilized in this advanced cavity, and the stable frequency is then transferred to the clock transition in strontium optical lattice clocks via a frequency-doubling process. We have meticulously minimized and assessed the technical noise contributions through comparisons with an ultrastable reference laser that is locked to a commercially available 30-cm cavity. The frequency instability of the system is rigorously evaluated using a three-cornered-hat method. The results demonstrate that the laser frequency instability remains below 2 × 10-16 for averaging times ranging from 1 to 50 s. These findings underscore the significant potential of room-temperature cavities with crystalline coatings in high-precision metrology and pave the way for further improvements in optical lattice clocks.

Developing a modified textbook outcome for elderly patients with gastric cancer: a multi-center study.

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.

BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

Effectiveness of onsite and online education in enhancing knowledge and use of human immunodeficiency virus pre- and post-exposure prophylaxis.

BACKGROUND: Enhancing awareness and use of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is vital to curb human immunodeficiency virus (HIV) spread. High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group. AIM: To investigate the effects of both onsite and online health education on the knowledge of, and willingness to use, PrEP and PEP among individuals receiving PEP services. METHODS: Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing, conducted from January 1 to June 30, 2022. Health education was provided both onsite and online during follow-up. Surveys assessing knowledge of, and willingness to use, PrEP/PEP were administered at baseline and again at 24 wk post-intervention. RESULTS: A total of 112 participants were enrolled in the study; 105 completed the follow-up at week 24. The percentage of participants with adequate knowledge of, and willingness to use, PrEP significantly increased from 65.2% and 69.6% at baseline to 83.8% and 82.9% at the end of the intervention (both P < 0.05). Similarly, those with adequate knowledge of, and willingness to use, PEP increased from 74.1% and 77.7% at baseline to 92.4% and 89.5% at week 24 (P < 0.05). Being between 31 years and 40 years of age, having a postgraduate degree or higher, and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP (both P < 0.05). CONCLUSION: The findings show that both onsite and online health education significantly improved the knowledge of, and increased willingness to use, PrEP and PEP in individuals utilizing PEP services.

The first large scale rDNA amplicon database of soil microbiomes from Pamir Plateau, China.

The Eastern Pamir, distinguished with high altitude, extremely arid and cold climate, limited nutrients and sparse vegetation, is a unique ecological reservoir. Microbial communities play a central role in maintaining Eastern Pamir's ecosystem functioning. Despite the ecological significance, due to the difficulty of sample collection and microbial isolation, the microbial diversity and its functionality at the Pamir Plateau have been rarely documented. To fill this gap, 80 soil samples from 17 sites across different elevations were collected, performed the rDNA amplicon sequencing to present the first large-scale overview of bacterial, archaeal, and fungal communities in the Eastern Pamir. Microbiome analysis revealed that the bacteria Actinobacteria, Alphaproteobacteria and Bacteroidia, alongside such as archaea Nitrososphaeria and Halobacteria, and fungi including Dothideomycetes, Sordariomycetes and Eurotiomycetes were dominant lineages at class level in soil microbial communities. The community structure and biodiversity of soil microorganisms provided by this dataset would be pivotal for future studies aimed at understanding the biogeographical distribution, ecological functions and environmental responses of microbial communities of the Pamir Plateau.

Effect of steam explosion pretreatment on the fermentation characteristics of polysaccharides from tea residue.

Green tea residues are the by-product of tea processing and they contain a large number of bioactive ingredients. Steam explosion has been recognized as one of the most innovative pretreatments for modifying the physicochemical characteristic of polysaccharides from lignocellulosic materials. However, the comparison of biological activity of steam exploded (SE-GTR) and unexploded (UN-GTR) green tea residue polysaccharides was still unclear, which prompted the determination of the efficacy of steam explosion in tea residue resource utilization. In this study, the effects of two extracted polysaccharides UN-GTR and SE-GTR on human gut microbiota in vitro fermentation were conducted. The results showed that after steam explosion pretreatment, SE-GTR displayed more loose and porous structures, resulting in higher polysaccharide content (2483.44±0.5 µg/mg) compared to UN-GTR (1903.56±2.6 µg/mg). In addition, after 24 h fermentation, gut microbiota produced more beneficial metabolites by SE-GTR. The largest SCFAs produced among samples was acetic acid, propionic acid and butyric acid. Furthermore, SE-GTR could regulate the composition and diversity of microbial community, increasing the abundance of beneficial bacteria, such as Bifidobacterium. These results revealed that steam explosion pretreatment could be a promising and efficient approach to enhance the antioxidant activity and bioavailability of polysaccharides isolated from tea residues.

Terahertz spoof plasmonic neural network for diffractive information recognition and processing.

All-optical diffractive neural networks, as analog artificial intelligence accelerators, leverage parallelism and analog computation for complex data processing. However, their low space transmission efficiency or large spatial dimensions hinder miniaturization and broader application. Here, we propose a terahertz spoof plasmonic neural network on a planar diffractive platform for direct multi-target recognition. Our approach employs a spoof surface plasmon polariton coupler array to construct a diffractive network layer, resulting in a compact, efficient, and easily integrable architecture. We designed three schemes: basis vector classification, multi-user recognition, and MNIST handwritten digit classification. Experimental results reveal that the terahertz spoof plasmonic neural network successfully classifies basis vectors, recognizes multi-user orientation information, and directly processes handwritten digits using a designed input framework comprising a metal grating array, transmitters, and receivers. This work broadens the application of terahertz plasmonic metamaterials, paving the way for terahertz on-chip integration, intelligent communication, and advanced computing systems.

The mechanism of cancer-depression comorbidity.

Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.

Microscopic Study on Superexchange Dynamics of Composite Spin-1 Bosons.

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

[Clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency: an analysis of six cases]. / 3-ç”²åŸºå·´è±†é °è¾ é ¶Aç¾§åŒ–é ¶ç¼ºä¹ç—‡6ä¾‹æ‚£å„¿çš„ä¸´åºŠç‰¹å¾åŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To investigate the clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD). METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of six children with MCCD who attended Children's Hospital Affiliated to Zhengzhou University from January 2018 to October 2023. RESULTS: Among the six children with MCCD, there were 4 boys and 2 girls, with a mean age of 7 days at the time of attending the hospital and 45 days at the time of confirmed diagnosis. Of all children, one had abnormal urine odor and five had no clinical symptoms. All six children had increases in blood 3-hydroxyisovaleryl carnitine and urinary 3-hydroxyisovaleric acid and 3-methylcrotonoylglycine, and five of them had a reduction in free carnitine. A total of six mutations were identified in the MCCC1 gene, i.e., c.1630del(p.R544Dfs*2), c.269A>G(p.D90G), c.1609T>A(p.F537I), c.639+2T>A, c.761+1G>T, and c.1331G>A(p.R444H), and three mutations were identified in the MCCC2 gene, i.e., c.838G>T(p.D280Y), c.592C>T(p.Q198*,366), and c.1342G>A(p.G448A). Among these mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I) had not been previously reported in the literature. There was one case of maternal MCCD, and the child carried a heterozygous mutation from her mother. Five children with a reduction in free carnitine were given supplementation of L-carnitine, and free carnitine was restored to the normal level at the last follow-up visit. CONCLUSIONS: This study identifies two new mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I), thereby expanding the mutation spectrum of the MCCC1 gene. A combination of blood amino acid and acylcarnitine profiles, urine organic acid analysis, and genetic testing can facilitate early diagnosis and treatment of MCCD, and provide essential data for genetic counseling.

A prediction model based on computed tomography characteristics for identifying malignant from benign sub-centimeter solid pulmonary nodules.

Background: Distinguishing benign from malignant sub-centimeter solid pulmonary nodules (SSPNs) continues to be challenging in clinical practice. Earlier diagnosis is crucial for improving patient survival and prognosis. This study aimed to investigate the risk factors of malignant SSPNs and establish and validate a prediction model based on computed tomography (CT) characteristics to assist in their early diagnosis. Methods: A total of 261 consecutive participants with 261 SSPNs were retrospectively recruited between January 2012 and July 2023 from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Center 1), including 161 malignant lesions and 100 benign lesions. Patients were randomly assigned to the training set (n=183) and validation set (n=78) according to a 7:3 ratio. Malignant nodules were confirmed by pathology; and benign nodules were confirmed by follow-up or pathology. Clinical data and CT features were collected to estimate the independent predictors of malignancy of SSPN with multivariate logistic analysis. A clinical prediction model was subsequently established by logistic regression. Furthermore, an additional 69 consecutive patients with 69 SSPNs from The Fourth Hospital of Hebei Medical University (Center 2) between January 2022 and December 2022 were retrospectively included as an external cohort to validate the predictive efficacy of the model. The performance of the prediction model was assessed by sensitivity, specificity, and the area under the receiver operating characteristic curve. Results: There were 113 (61.7%), 48 (61.5%) and 28 (40.6%) malignant SSPNs in the training, internal and external validation sets, respectively. Multivariate logistic analysis revealed four independent predictors of malignant SSPNs: tumor-lung interface (P=0.002), spiculation (P=0.04), air bronchogram (P=0.047), and invisible at the mediastinal window (P=0.003). The area under the curve (AUC) for the prediction model in the training set was 0.875 [95% confidence interval (CI): 0.818, 0.933]; and the sensitivity and specificity were 94.7% and 68.6%, respectively. The AUCs in the internal and external validation set were (0.781; 95% CI: 0.664, 0.897) and (0.873; 95% CI: 0.791, 0.955), respectively; the sensitivity and specificity were 66.7% and 83.3% for the internal validation data, and 100.0% and 61.0% for the external validation data, respectively. Conclusions: The prediction model based on CT characteristics could be helpful for distinguishing malignant SSPNs from benign ones.

Preparation of Pt and bamboo charcoal co-modified TiO2 for formaldehyde sensing at room temperature.

Anatase TiO2 has evolved into one of the most attractive materials for gas sensing owing to its strong oxidation activity and excellent sensing properties. In this study, we prepared Pt and bamboo charcoal co-modified nano-TiO2 using a one-pot hydrothermal process and applied it to detect formaldehyde. The successful incorporation of the precious metal Pt and bamboo charcoal onto TiO2 was confirmed by scanning electron microscope, transmission electron microscopy, energy dispersive spectrometer, X-ray diffraction and X-ray photoelectron spectroscopy. Detailed analysis revealed a homogeneous distribution of Pt nanoparticles and bamboo charcoal on the TiO2 surface, which significantly improved the surface area and facilitated gas adsorption. These modifiers significantly enhanced the response of TiO2 to formaldehyde, for instance, the response signal increased fourfold, while the response time decreased from 91 to 68 s. The sample with 0.5@Pt and 0.5@C bamboo charcoal performed the best, showcasing the synergistic effect of metal nanoparticles and carbonaceous materials on gas-sensing properties. Our work highlighted the potential of using biomass-derived carbon to enhance the detection of formaldehyde and demonstrated the importance of material characteristics in designing effective gas sensors.

A bioinspired switchable adhesive patch with adhesion and suction mechanisms for laparoscopic surgeries.

Medical adhesives play an important role in clinical medicine because of their flexibility and convenient operation. However, they are still limited to laparoscopic surgeries, which have demonstrated urgent demand for liver retraction with minimal damage to the human body. Here, inspired by the suction cup structure of octopus, an adhesive patch with excellent mechanical properties, robust and switchable adhesiveness, and biocompatibility is proposed. The adhesive patch is combined by the attachment body mainly made of poly(acrylic acid) grafted with N-hydroxysuccinimide ester, crosslinked biodegradable gelatin methacrylate and biodegradable biopolymer gelatin to mimic the adhesive sucker rim, and the temperature-sensitive telescopic layer of microgel-crosslinked poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) to shrink and form internal cavity with reduced pressure. Through mechanical tests, adhesion evaluation, and biocompatibility analysis, the bioinspired adhesive patch has demonstrated its capacity not only in adhesion to tissues but also in potential treatment for medical applications, especially laparoscopic technology. The bioinspired adhesive patch can break through the limitations of traditional retraction methods, and become an ideal candidate for liver retraction in laparoscopic surgery and related clinical medicine.

Applications of Biosensors in Bladder Cancer.

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

[Effects of Questionnaire-Based Psychological Survey Methods on the Evaluation Results in a Patient Cohort].

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Photoelectrochemical Solution Gated Graphene Field-Effect Transistor Functionalized by Enzymatic Cascade Reaction for Organophosphate Detection.

Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing significant modulation of the drain current with minimal gate voltage. However, few studies have focused on light-matter interplay gating control for SGGT. Herein, this challenge is addressed by creating an innovative photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) functionalized with enzyme cascade reactions (ECR) for Organophosphorus (OPs) detection. The ECR system, consisting of acetylcholinesterase (AChE) and CuBTC nanomimetic enzymes, selectively recognizes OPs and forms o-phenylenediamine (oPD) oligomers sediment on the PEC electrode, with layer thickness related to the OPs concentration, demonstrating time-integrated amplification. Under light stimulation, the additional photovoltage generated on the PEC gate electrode is influenced by the oPD oligomers sediment layer, creating a differentiated voltage distribution along the gate path. PEC-SGGT, inherently equipped with built-in amplification circuits, sensitively captures gate voltage changes and delivers output with an impressive thousandfold current gain. The seamless integration of these three amplification modes in this advanced sensor allows a good linear range and highly sensitive detection of OPs, with a detection limit as low as 0.05 pm. This work provides a proof-of-concept for the feasibility of light-assisted functionalized gate-controlled PEC-SGGT for small molecule detection.