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A tripodal fluoroionophore based on a hexasubstituted benzene unit having two trifluoroacetophenone groups and a pyrenyl moiety was synthesized, and its characteristics as fluorogenic reagent or component of an ISE or optode membrane towards several underivatized amino acids were examined. In a solid–liquid extraction experiment in acetonitrile, the fluorescence enhancement response was observed in the order of Phe, Cys, and Gly. On the other hand, the PVC-based polymeric membrane applied in ISE showed Phe selectivity with a monoanionic Nernstian response, supporting the assumption that the ionophore binds Phe in its anionic form. It is demonstrated that the optode membrane based on this fluoroionophore shows fluorescence enhancement response towards Phe or Cys in a flow-system.

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited. As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qingwei Li reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Chinese National Natural Science Foundation. Jiali Lu reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Applied Basic Research Project of the Science and Technology Department of Liaoning Province. Jiali Lu reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by the Project of the Educational Department of Liaoning Province. Xiaoping Song reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Dalian Youth Science and Technology Star Fund Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

Lodging largely affects yield, quality and mechanical harvesting of maize. Stalk strength is one of the major factors that affect maize lodging. Although plant cell wall components including lignin and cellulose were known to be associated with stalk strength and lodging resistance, spatial accumulation of specific lignin monomers and cellulose in different tissues and their association with stalk strength in maize was not clearly understood. In this study, we found that both G and S lignin monomers accumulate highest in root, stem rind and leaf vein. Consistently, most lignin biosynthetic genes were expressed higher in root and stem than in other tissues. However, cellulose appears to be lowest in root. There are only mild changes of G lignin and cellulose in different internodes. Instead, we noticed a dramatic decrease of S-lignin accumulation and lignin biosynthetic gene expression in 2 nd to 4 th internodes wherein stem breakage usually occurs, thereby revealing a few candidate lignin biosynthetic genes associated with stalk strength. Moreover, stalk strength is positively correlated with G, S lignin, and cellulose, but negatively correlated with S/G ratio based on data of maize lines with high or low stalk strength. Loss-of-function of a caffeic acid o-methyltransferase (COMT), which is involved in S lignin biosynthesis, in the maize bm3 mutant, leads to lower stalk strength. Our data collectively suggest that stalk strength is determined by tissue-specific accumulation of lignin monomers and cellulose, and manipulation of the cell wall components by genetic engineering is vital to improve maize stalk strength and lodging resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC)., Method: A total of 181 Chinese pregnant women (M age = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed., Results: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (β = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms., Conclusions: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cooked off-flavor was produced during the processing of concentrated peach puree (CPP), which led to aroma deterioration. Enzymatic treatment was beneficial in eliminating off-flavors and improving the aroma quality. Herein, the efficacy of glycosidase (AR2000), glucose oxidation (GOD), and their combination on the inhibition of off-flavors and aroma enhancement were evaluated. Compared with CPP, contents of benzaldehyde, benzyl alcohol, nonanal, and linalool increased by 198%, 1222%, 781%, and 71% after AR2000 treatment via the metabolisms of shikimate, glucose, linoleic acid, and linolenic acid, leading to the strengthening of floral and grassy. Due to the removal of 1-octen-3-one via linolenic acid metabolism, cooked off-flavor could be significantly weakened by GOD. Furthermore, Furthermore, the combination of AR2000 and GOD could not only inhibit the production of 1-octen-3-one to weaken the cooked note but also enhance grassy and floral attributes via the increase of aldehydes and alcohols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: The therapeutic needs of women with diminished ovarian reserve (DOR), coupled with the increasing application of acupuncture in improving ovarian function, have highlighted the need to verify the efficacy and safety of acupuncture for DOR. This study aims to provide high-quality evidence by evaluating both ovarian reserve and in vitro fertilisation (IVF) outcomes., Methods and Analysis: A large-scale, multicentre, randomised controlled trial will be carried out across seven hospitals in China. 400 women with DOR will be randomised in a 1:1 ratio to an acupuncture group or a sham acupuncture group. Acupuncture or sham acupuncture will consist of 36 sessions per participant over 12 weeks. The primary outcome will be the change in antral follicle count (AFC) at week 12 from baseline. Secondary outcomes are AFC at week 24, the serum levels of basal follicle-stimulating hormone and anti-Mullerian hormone at weeks 12 and 24, the scores of the Self-Rating Anxiety Scale at weeks 12 and 24, clinical pregnancy rate, and IVF embryo transfer related outcomes. Any adverse events during treatment will be documented., Ethics and Dissemination: The study protocol has been approved by all the participating institutions. Written informed consent will be obtained prior to participant enrolment. The results of this study will be published in peer-reviewed publications., Trial Registration Number: ChiCTR2200062295 PROTOCOL VERSION: V2.0-20220317., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ethical behaviour in nursing practice is integral to establishing a harmonious nurse-patient relationship and improving the quality of care. A multitude of factors shapes such behaviour. Therefore, it is crucial to understand the interplay between these factors. Research objectives: This study aimed to explore the mechanisms underlying the influence of moral sensitivity on nurses' ethical behaviour and clarify the mediating role of moral courage. Research design: This cross-sectional quantitative study was conducted between July and August 2023. Participants and Research Context: The sample comprised 465 clinical nurses from three tertiary hospitals in Zhengzhou City, Henan Province, China. Data were collected using the Chinese version of the Moral Sensitivity Questionnaire-Revised Version, Nurses' Moral Courage Scale, and Ethical Behaviour Scale for Nurses. Data analysis was performed with SPSS 26.0 and AMOS 24.0, using descriptive statistics, Pearson correlation analysis, structural equation modelling, and bootstrapping methods. Ethical considerations: This study was approved by the Ethical Review Committee of Life Sciences of Zhengzhou University, China. Results: The participants were predominantly female (95.1%), with a mean age of 31.9 years. Moral courage and moral sensitivity were positively correlated with ethical behaviour. Moral sensitivity was positively associated with moral courage. Moral courage partially mediates the relationship between moral sensitivity and ethical behaviour. The indirect effect of nurses' moral sensitivity on ethical behaviour was quantified through moral courage (indirect effect = 0.290). Conclusion: Moral courage intermediates nurses' moral sensitivity and ethical behaviour. This conclusion provides nursing administrators with the insight that improving clinical nurses' moral sensitivity and courage can contribute to ensuring appropriate ethical behaviour., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T FH ) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and T FH cells was found within T cell zones of colonic lymphoid follicles. T FH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted T FH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, T FH cells transdifferentiated into long-lived pathogenic T H 1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of T FH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Developing microbial consortiums is necessary for microbial enhanced oil recovery (MEOR) in heavy crude oil production. The aqueous phase of produced fluid has long been considered an ideal source of microorganisms for MEOR. However, it is recently found that rich microorganisms (including hydrocarbon-degrading bacteria) are present in the crude oil phase, which is completely different from the aqueous phase of produced fluid. So, in this study, the microbial consortia from the crude oil phase of produced fluids derived from four wells were enriched, respectively. The microbial community structure during passage was dynamically tracked, and the response of enriched consortia to successive disturbance of environmental factors was investigated. The results showed the crude oil phase had high microbial diversity, and the original microbial community structure from four wells was significantly different. After ten generations of consecutive enrichment, different genera were observed in the four enriched microbial consortia, namely, Geobacillus, Bacillus, Brevibacillus, Chelativorans, Ureibacillus, and Ornithinicoccus. In addition, two enriched consortia (eG1614 and eP30) exhibited robustness to temperature and oxygen perturbations. These results further suggested that the crude oil phase of produced fluids can serve as a potential microbial source for MEOR., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

3-phosphoinositide-dependent protein kinase-1 (PDK-1) is a key kinase regulating the activity of the PI3K/AKT pathway and a major regulator of the AGC protein kinase family. It is essential in the physiological activities of cells, embryonic development, individual development and immune response. In this study, we have identified for the first time an analogue of PDK-1 in the most primitive vertebrate, lamprey, and named it PDK-1-like. The protein sequence similarity of lamprey PDK-1-like to human, mouse, chicken, African xenopus and zebrafish PDK-1 were 64.4 %, 64.5 %, 65.0 %, 61.3 % and 63.2 %, respectively. The phylogenetic tree showed that PDK-1-like of lamprey were located at the base of the vertebrate branch, in line with the trend of biological evolution. Meanwhile, homology analysis showed that PDK-1 proteins across species shared a conserved kinase structural domain and a Pleckstrin Homology (PH) domain. Genomic synteny analysis revealed that the large-scale duplication blocks were not found in lamprey genome and neighbor genes of lamprey PDK-1-like presented dramatic differences compared with jawed vertebrates. More importantly, qPCR analysis showed that PDK-1-like was widely expressed in lamprey. Its mRNA expression levels varied in response to different pathogenic stimuli, and its expression was generally up-regulated under Polyinosinic-Polycytidylic acid (Poly(I:C)) stimulation. Pearson's correlation analysis showed that PDK-1-like was involved in co-expressed with MyD88-independent TLR-3 pathway during the immune response of lamprey, instead of MyD88-dependent TLR-3 pathway. In summary, our composite results offer valuable clues to the origin and evolution of PDK-1, and imply that PDK-1 s are among the most ancestral immune regulators in vertebrates., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Source-free domain adaptation (SFDA) shows the potential to improve the generalizability of deep learning-based face anti-spoofing (FAS) while preserving the privacy and security of sensitive human faces. However, existing SFDA methods are significantly degraded without accessing source data due to the inability to mitigate domain and identity bias in FAS. In this paper, we propose a novel Source-free Domain Adaptation framework for FAS (SDA-FAS) that systematically addresses the challenges of source model pre-training, source knowledge adaptation, and target data exploration under the source-free setting. Specifically, we develop a generalized method for source model pre-training that leverages a causality-inspired PatchMix data augmentation to diminish domain bias and designs the patch-wise contrastive loss to alleviate identity bias. For source knowledge adaptation, we propose a contrastive domain alignment module to align conditional distribution across domains with a theoretical equivalence to adaptation based on source data. Furthermore, target data exploration is achieved via self-supervised learning with patch shuffle augmentation to identify unseen attack types, which is ignored in existing SFDA methods. To our best knowledge, this paper provides the first full-stack privacy-preserving framework to address the generalization problem in FAS. Extensive experiments on nineteen cross-dataset scenarios show our framework considerably outperforms state-of-the-art methods.

Background: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS)., Methods: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC)., Results: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels., Conclusions: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia., (© 2024. The Author(s).)

Haloarchaea with the capacity to degrade alkanes is promising to deal with petroleum pollution in hypersaline environments. However, only a limited number of haloarchaeal species are investigated, and their pathway and mechanism for alkane degradation remain unclear. In this study, Halogranum rubrum RO2-11, a haloarchaeal strain, verified the ability to degrade kerosene and hexadecane in 184 g/L NaCl, with 53% and 52% degradation rates after 9 and 4 days, respectively. Genome sequencing and gene annotation indicated that strain RO2-11 possesses a complete potential alkane-degrading pathway, of which alkane hydroxylases may include CYP450, AlmA, and LadA. Transcriptome and metabolome analyses revealed that the upregulation of related genes in TCA cycle, lysine biosynthesis, and acetylation may help improve hexadecane degradation. Additionally, an alternative degrading pathway of hexadecane based on dual-terminal β-oxidation may occur in strain RO2-11. It is likely to be the first report of alkane degradation by the genus Halogranum, which may be helpful for applications of oil-pollution bioremediation under high-salt conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Social anxiety disorder (SAD) is one of the most prevalent psychological disorders and generally co-occurs with elevated shame levels. Previous shame-specific interventions could significantly improve outcomes in social anxiety treatments. Recent review suggests that integrating a more direct shame intervention could potentially increase the effectiveness of cognitive behavioral therapy. Web-based cognitive behavioral therapy (WCBT) has proven efficacy, sustaining benefits for 6 months to 4 years. Previous evidence indicated that shame predicted the reduction of social anxiety and mediated between engagements in exposure and changes in social anxiety during WCBT., Objective: This study aimed to design a shame intervention component through a longitudinal study and conduct a randomized controlled trial to investigate the effectiveness of a shame intervention component in reducing social anxiety symptoms and shame experience in a clinical sample of people with SAD., Methods: The development of a shame intervention component was informed by cognitive behavioral principles and insights from longitudinal data that measured the Experience of Shame Scale (ESS), the Coping Styles Questionnaire, and the Social Interaction Anxiety Scale (SIAS) in 153 participants. The psychoeducation, cognitive construct, and exposure sections were tailored to focus more on shame-related problem-solving and self-blame. A total of 1220 participants were recruited to complete questionnaires, including the ESS, the SIAS, the Social Phobia Scale (SPS), and diagnostic interviews. Following a 2-round screening process, 201 participants with SAD were randomly assigned into a shame WCBT group, a normal WCBT group, and a waiting group. After the 8-week WCBT intervention, the participants were asked to complete posttest evaluations, including the ESS, SIAS and SPS., Results: Participants in the shame WCBT group experienced significant reductions in shame levels after the intervention (ESS: P<.001; ηp2=0.22), and the reduction was greater in the shame intervention group compared to normal WCBT (P<.001; mean deviation -12.50). Participants in both the shame WCBT and normal WCBT groups experienced significant reductions in social anxiety symptoms (SIAS: P<.001; ηp2=0.32; SPS: P<.001; ηp2=0.19) compared to the waiting group after intervention. Furthermore, in the experience of social interaction anxiety (SIAS), the shame WCBT group showed a higher reduction compared to the normal WCBT group (P<.001; mean deviation -9.58). Problem-solving (SE 0.049, 95% CI 0.025-0.217) and self-blame (SE 0.082, 95% CI 0.024-0.339) mediated the effect between ESS and SIAS., Conclusions: This is the first study to design and incorporate a shame intervention component in WCBT and to validate its efficacy via a randomized controlled trial. The shame WCBT group showed a significant reduction in both shame and social anxiety after treatment compared to the normal WCBT and waiting groups. Problem-solving and self-blame mediated the effect of shame on social anxiety. In conclusion, this study supports previous findings that a direct shame-specific intervention component could enhance the efficacy of WCBT., (©Xu Wen, Mengke Gou, Huijing Chen, Tomoko Kishimoto, Mingyi Qian, Jürgen Margraf, Thomas Berger. Originally published in JMIR Mental Health (https://mental.jmir.org).)

CD8 + T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8 + T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Immunotherapy is an important approach in cancer treatment. Transdermal administration is emerging as a promising method for delivering immunotherapeutics. Dissolving microneedles are made mainly of soluble or biodegradable polymers and have garnered widespread attention due to their painlessness, safety, convenience, excellent drug loading capacity, and easy availability of various materials, making them an ideal transdermal delivery system. This review comprehensively summarized the preparation methods, materials, and applications of dissolving microneedles in cancer vaccines, immune checkpoint inhibitors, and adoptive cell therapy. Additionally, the challenges and perspectives associated with their future clinical translation are discussed.

Previous laboratory-scale studies have consistently shown that carbon-based conductive materials can notably improve the anaerobic digestion of food waste, typically employing reactors with regular capacity of 1-20 L. Furthermore, incorporating riboflavin-loaded conductive materials can further address the imbalance between fermentation and methanogenesis in anaerobic systems. However, there have been few reports on pilot-scale investigation. In this study, a 10 m 2 of riboflavin modified carbon cloth was incorporated into a pilot-scale (2 m 3 ) food waste anaerobic reactor to improve its treatment efficiency. The study found that the addition of riboflavin-loaded carbon cloth can increase the maximum organic loading rate (OLR) by 40% of the pilot-scale reactor, compared to the system using carbon cloth without riboflavin loading, while ensuring efficient operation of the reaction system, effectively alleviating system acidification, sustaining methanogen activity, and increasing daily methane production by 25%. Analysis of the microbial community structure revealed that riboflavin-loaded carbon cloth enriched the methanogenic archaea in the genera of Methanothrix and Methanobacterium , which are capable of extracellular direct interspecies electron transfer (DIET). And metabolic pathway analysis identified the methane production pathway, highly enriched on the reduction of acetic acid and CO 2 at riboflavin-loaded carbon cloth sample. The expression levels of genes related to methane production via DIET pathway were also significantly upregulated. These results can provide important guidance for the practical application of food waste anaerobic digestion engineering., Competing Interests: HX and HW were employed by Qinglin Chuangneng (Shanghai) Technology Co., Ltd. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Li, Huang, Li, Gou, Xu, Wu, Sun, Qiu and Dang.)

Non-volatiles offer some insight into the formation of aroma-active components in peach puree (PP), but more depth investigation is still needed. Formation pathways of key aroma-active and off-flavor components in PP during thermal concentration (PP + C) and sterilization (PP + C + S) are unclear. Therefore, GC-O-MS combined with UPLC-MS/MS was used to identify the volatile and nonvolatile components and their formation pathways. Among the 36 aroma-active compounds, the contents of γ-decalactone, hexyl acetate, leaf acetate, hexanal, and 1-hexanol (odor activity value ≥ 1) decreased by 46 %, 100 %, 100 %, 92 %, and 100 % between PP and PP + C + S, causing the weakening of "green" and "fruity" attributes. Off-flavor components including 1-octen-3-one, isobutyric acid, isothiazole, and isovaleric acid were identified during thermal processing. 1-Octen-3-one content increased by 75 % from PP to PP + C + S through linolenic acid metabolism, which contributed to "cooked"; the formation of isobutyric and isovaleric acids, isothiazole, resulted in the enhancement of "sour/rancid" via serine and leucine metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore-forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin, thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non-viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imbalance in the pathophysiological mechanism of schizophrenia. This study aimed to explore the little-known area regarding the composite score of peripheral cytokines, the IRS/CIRS, and its correlation with white matter integrity and the specific microstructures most affected in schizophrenia. First-episode patients with schizophrenia (FEPS, n = 94) and age- and sex-matched healthy controls (HCs, n = 50) were enrolled in this study. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The whole brain white matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging (DTI) using a 3-T Prisma MRI scanner. The IRS/CIRS in FEPS was significantly higher than that in HCs (p = 1.5 × 10 -5 ) and Cohen's d effect size was d = 0.74. FEPS had a significantly lower whole-brain white matter average FA (p = 0.032), which was negatively associated with IRS/CIRS (p = 0.029, adjusting for age, sex, years of education, BMI, and total intracranial volume), but not in the HCs (p > 0.05). Among the white matter microstructures, only the cortico-spinal tract was significantly correlated with IRS/CIRS in FEPS (r =  - 0.543, p = 0.0009). Therefore, elevated IRS/CIRS may affect the white matter in FEPS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Guided bone regeneration (GBR) is one of the most widely used and thoroughly documented alveolar bone augmentation surgeries. However, implanting GBR membranes inevitably triggers an immune response, which can lead to inflammation and failure of bone augmentation. It has been shown that GBR membranes may significantly improve in vivo outcomes as potent immunomodulators, rather than solely serving as traditional barriers. Macrophages play crucial roles in immune responses and participate in the entire process of bone injury repair. The significant diversity and high plasticity of macrophages complicate our understanding of the immunomodulatory mechanisms underlying GBR. This review provides a comprehensive summary of recent findings on the potential role of macrophages in GBR for bone defects in situ. Specifically, macrophages can promote osteogenesis or fibrous tissue formation in bone defects and degradation or fibrous encapsulation of membranes. Moreover, GBR membranes can influence the recruitment and polarization of macrophages. Therefore, immunomodulating GBR membranes are primarily developed by improving macrophage recruitment and aggregation as well as regulating macrophage polarization. However, certain challenges remain to be addressed in the future. For example, developing more rational and sophisticated sequential delivery systems for macrophage activation reagents; addressing the interference of bone graft materials and dental implants; and understanding the correlations among membrane degradation, macrophage responses, and bone regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gou, Wang, Xie and Song.)

Background: Atherosclerosis are well established risk factors for ischemic stroke, however the association between alcohol consumption and atherosclerosis is controversial. This study aims to explore the potential correlation between alcohol consumption and cerebral stenosis in patients with acute ischemic stroke and transient ischemic attack (TIA)., Methods: Nine hundreds and eighty-eight patients with first acute ischemic stroke attack or TIA were recruited retrospectively. Alcohol consumption was classified into five consumption categories (non-drinkers, occasional drinkers, < 140 g per week [mild drinkers], 140-279 g per week [moderate drinkers], ≥ 280 g per week [heavy drinkers]). Computed tomography angiography (CTA) and digital subtraction angiography (DSA) were utilized to assess the carotid and cerebral artery in all patients. Five-step scale for degree of stenosis was applied: normal (0, 0 points), mild (< 50%, 1 point), moderate (50-69%, 2 points), severe (70-99%, 3 points), and occlusion (100%, 4 points)., Results: The carotid and cerebral artery stenosis scores were positively correlated with moderate alcohol consumption (B = 1.695, P < 0.001). Compared with nondrinkers, moderate alcohol consumption had significant increasing risk of moderate carotid and cerebral artery stenosis (OR = 4.28, 95% CI: 1.47-12.49, P = 0.008) and severe stenosis (OR = 4.24, 95% CI: 1.55-11.64, P = 0.005) and occlusion (OR = 3.87, 95% CI: 1.65-9.06, P = 0.002). Compared with nondrinkers, heavy alcohol consumption patients had significant higher risk of carotid and cerebral artery occlusion (OR = 2.71, 95% CI: 1.36-5.41, P = 0.005)., Conclusions: Higher alcohol consumption may associate with higher risk and more severity of carotid and cerebrovascular stenosis., (© 2024. The Author(s).)

Objective: It is of positive significance for clinical management to infer the changes of BPV and blood Hcy in the risk of cardiovascular disease progression in patients with hypertension by ambulatory blood pressure test. We aimed to explore the correlation of homocysteine and blood pressure variability with left ventricular hypertrophy in patients with hypertension and carotid atherosclerosis., Methods: A total of 333 elderly hypertensive patients admitted to Jinniu District People's Hospital in Chengdu from February 2020 to December 2021 were selected as the study subjects. They were divided into the pure hypertension group and hypertension combined with the carotid atherosclerosis group. In addition, the two groups were divided into the hypertension combined with left ventricular remodeling subgroup and the hypertension without left ventricular remodeling subgroup. Plasma Hcy levels were measured on a BECKMAN AU 680 automated biochemistry analyzer. Ambulatory blood pressure was measured by HINGMED ABP-03 monitoring system. IMT measurement was performed using a GE LOGIQ E9 ultrasound. Left ventricular diastolic function measurement was performed using a GE LOGIQ E9 ultrasound., Results: Blood Hcy, 24-h mean SBP, 24-h mean DBP, 24-h SBP coefficient of variation, and 24-h DBP coefficient of variation were significantly higher in hypertension combined with the carotid atherosclerosis group than the pure hypertension group (P < .05). Moreover, LVMI, E/A, and E/e were greater in the carotid atherosclerosis group than in the normal carotid group (P < .05). IMT, blood Hcy, 24-h mean SBP, 24-h mean DBP, 24-h SBP coefficient of variation, 24-h DBP coefficient of variation, E/A, and E/e were significantly higher in the hypertensive combined with left ventricular remodeling subgroup than in the non-left ventricular remodeling subgroup (P < .05). IMT was positively correlated with blood Hcy, 24-h SBP, 24-h DBP, 24-h SCV, 24-h DCV, LVMI, E/A, and E/e (P < .05)., Conclusion: There was a position correlation of Hcy and BPV with left ventricular hypertrophy in patients with hypertension combined with carotid atherosclerosis.

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD)., Methods: Patients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication., Results: The levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms., Conclusions: Patients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Huang, Zhang, Zhou, Tong, Chen, Gou, Tian, Li, Luo, Tian, Hong, Li and Tan.)

Background: Immune checkpoint inhibitors have been approved for first- and third-line treatment of advanced gastric cancer. However, pembrolizumab alone in the second line did not improve overall survival compared to chemotherapy in the KEYNOTE-061 study. In this study, we aimed to explore the efficacy and safety of a three-drug regimen of PD-1 inhibitor combined with albumin paclitaxel and apatinib (a VEGFR inhibitor) for the second-line treatment of patients with metastatic gastric cancer (mGC)., Methods: This was a single-center, single-arm, phase II clinical study. Patients with mGC with stable microsatellite and negative HER-2 expression who failed first-line chemotherapy were enrolled. The enrolled patients were treated with PD-1 inhibitor (selected according to patients' requirements) in combination with albumin paclitaxel (125 mg/m 2 , intravenously, days 1 and 8, or 250 mg/m 2 , intravenously, day 1) and apatinib (250 or 500 mg, orally, days 1-21) every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response, and adverse events (AEs)., Results: From July 11, 2019, to October 13, 2022, a total of 43 patients were enrolled, of whom 10 were PD-L1 negative, 11 were PD-L1 positive, and 22 had unknown PD-L1 expression. As of the data cutoff on April 1st, 2023, nine patients had partial response, 29 had stable disease, and five experienced progressive disease, with the ORR of 20.9% and DCR of 88.3%. The median PFS was 6.2 months (95% CI, 3.9-9.3), and the median OS was 10.1 months (95% CI, 7.5-14.1). All patients suffered from alopecia and neurotoxicity. The other main AEs of grade 1 or 2 were bone marrow suppression (N = 21, 48.8%), hand-foot reaction (N = 19, 44.2%), hypertension (N = 18, 41.9%), hypothyroidism (N = 11, 25.6%), gastrointestinal bleeding (N = 3, 7.0%), and liver function damage (N = 5, 11.6%). Two patients reported grade 3-4 immune-related liver damage., Conclusion: Second-line PD-1 inhibitor combined with albumin paclitaxel and apatinib showed certain efficacy and safety in patients with mGC., Trial Registration: Clinical trials, NCT04182724. Registered 27 November 2019; retrospectively registered, https://clinicaltrials.gov/study/NCT04182724., (© 2024. The Author(s).)

The plant cuticle is essential in plant defense against biotic and abiotic stresses. To systematically elucidate the genetic architecture of maize (Zea mays L.) cuticular wax metabolism, 2 cuticular wax-related traits, the chlorophyll extraction rate (CER) and water loss rate (WLR) of 389 maize inbred lines, were investigated and a genome-wide association study (GWAS) was performed using 1.25 million single nucleotide polymorphisms (SNPs). In total, 57 nonredundant quantitative trait loci (QTL) explaining 5.57% to 15.07% of the phenotypic variation for each QTL were identified. These QTLs contained 183 genes, among which 21 strong candidates were identified based on functional annotations and previous publications. Remarkably, 3 candidate genes that express differentially during cuticle development encode β-ketoacyl-CoA synthase (KCS). While ZmKCS19 was known to be involved in cuticle wax metabolism, ZmKCS12 and ZmKCS3 functions were not reported. The association between ZmKCS12 and WLR was confirmed by resequencing 106 inbred lines, and the variation of WLR was significant between different haplotypes of ZmKCS12. In this study, the loss-of-function mutant of ZmKCS12 exhibited wrinkled leaf morphology, altered wax crystal morphology, and decreased C32 wax monomer levels, causing an increased WLR and sensitivity to drought. These results confirm that ZmKCS12 plays a vital role in maize C32 wax monomer synthesis and is critical for drought tolerance. In sum, through GWAS of 2 cuticular wax-associated traits, this study reveals comprehensively the genetic architecture in maize cuticular wax metabolism and provides a valuable reference for the genetic improvement of stress tolerance in maize., Competing Interests: Conflict of interest statement. The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The cooperation among members of microbial communities based on the exchange of public goods such as 20 protein amino acids (AAs) has attracted widespread attention. However, little is known about how AAs availability affects interactions among members of complex microbial communities and the structure and function of a community., Methods: To investigate this question, trace amounts of AAs combinations with different synthetic costs (low-cost, medium-cost, high-cost, and all 20 AAs) were supplemented separately to acetate-degrading thermophilic methanogenic reactors, and the differences in microbial community structure and co-occurring networks of main members were compared to a control reactor without AA supplementation., Results: The structure of the microbial community and the interaction of community members were influenced by AAs supplementation and the AAs with different synthetic costs had different impacts. The number of nodes, links, positive links, and the average degree of nodes in the co-occurrence network of the microbial communities with AAs supplementation was significantly lower than that of the control without AAs supplementation, especially for all 20 AAs supplementation followed by the medium- and high-cost AAs supplementation. The average proportion of positive interactions of microbial members in the systems supplemented with low-cost, medium-cost, high-cost, all AAs, and the control group were 0.42, 0.38, 0.15, 0.4, and 0.45, respectively. In addition, the ecological functions of community members possibly changed with the supplementation of different cost AAs., Discussion: These findings highlight the effects of AAs availability on the interactions among members of complex microbial communities, as well as on community function., Competing Interests: QZ was employed by the company SINOPEC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yao, Zhang, Gou and Tang.)

Copine proteins are highly conserved and ubiquitously found in eukaryotes, and their indispensable roles in different species were proposed. However, their exact function remains unclear. The phytohormone brassinosteroids (BRs) play vital roles in plant growth, development and environmental responses. A key event in effective BR signaling is the formation of functional BRI1-SERK receptor complex and subsequent transphosphorylation upon ligand binding. Here, we demonstrate that BONZAI (BON) proteins, which are plasma membrane-associated copine proteins, are critical components of BR signaling in both the monocot maize and the dicot Arabidopsis. Biochemical and molecular analyses reveal that BON proteins directly interact with SERK kinases, thereby ensuring effective BRI1-SERK interaction and transphosphorylation. This study advances the knowledge on BR signaling and provides an important target for optimizing valuable agronomic traits, it also opens a way to study steroid hormone signaling and copine proteins of eukaryotes in a broader perspective., (© 2024. The Author(s).)

Background: The immune-inflammatory response system (IRS) and kynurenine pathway (KP) have been implicated in the pathophysiology of schizophrenia. Studies have shown inflammation-related effects on KP metabolism in patients with schizophrenia. This study investigated the relationship between KP metabolites, IRS, and the compensatory immune-regulatory reflex system (CIRS) in patients with treatment-resistant schizophrenia (TRS)., Methods: Patients with (n = 53) and without TRS (n = 47), and healthy controls (HCs, n = 49) were enrolled. We quantified plasma levels of pro-inflammatory cytokines (interleukin [IL]-1β, IL-2, IL-6, soluble(s)IL-6 receptor, IL-8, IL-12, IL-17, IL-18, interferon-γ, and tumor necrosis factor[TNF]-α) and anti-inflammatory cytokines (IL-1 receptor antagonist, IL-4, IL-10, tumor growth factor [TGF]-β1, TGF-β2, soluble (s) IL-2 receptor subunit α, sIL-2 receptor subunit β, and sTNF-α receptor 1) and calculated the IRS/CIRS ratio. We also tested serum metabolites of the KP, including kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN), along with the QUIN/KYNA ratio., Results: Patients with TRS had significantly higher IRS/CIRS ratio than non-TRS patients (p = 0.002) and HCs (p = 0.007), and significantly lower KYN (p = 0.001) and KYNA (p = 0.01) levels than HCs. Binary logistic regression analysis revealed that a younger age at illness onset (odds ratio [OR] = 0.91, p = 0.02) and a higher IRS/CIRS ratio (OR = 1.22; p = 0.007) were risk factors for patients with TRS. After further adjusted for age of onset, the QUIN/KYNA ratio (β = 0.97; p = 0.02) significantly moderated the relationship between IRS/CIRS and TRS, showing that in the higher QUIN/KYNA condition, higher IRS/CIRS ratio were significantly and more likely to be associated with patients with TRS (β = 0.12, z = 3.19, p = 0.001), whereas in the low QUIN/KYNA condition, the association between IRS/CIRS ratio and TRS was weak and insignificant., Conclusions: The peripheral immune response was imbalanced in TRS and was preferentially directed towards the IRS compared to patients without TRS and healthy controls, which is likely to play a role in neurotoxicity. Additionally, peripheral KP activation was also imbalanced, as evidenced by significantly reduced KYN and KYNA levels in patients with TRS compared to healthy controls, but none of KP metabolisms were significantly difference in non-TRS patients compared to healthy controls. QUIN/KYNA ratio involving to the degree of activation of NMDA receptors, indicated the neurotoxic level of the KP activation. The interaction between IRS/CIRS and QUIN/KYNA ratio was significant in predicting TRS, and our findings suggest a potential role for the immune-kynurenine pathway in TRS pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Liver-expressed antimicrobial peptide 2 (LEAP2) is a member of the antimicrobial peptides family and plays a key role in the innate immune system of organisms. LEAP2 orthologs have been identified from a variety of fish species, however, its function in primitive vertebrates has not been clarified. In this study, we cloned and identified Lc-LEAP2 from the primitive jawless vertebrate lamprey (Lethenteron camtschaticum) which includes a 25 amino acids signal peptide and a mature peptide of 47 amino acids. Although sequence similarity was low compared to other species, the mature Lc-LEAP2 possesses four conserved cysteine residues, forming a core structure with two disulfide bonds between the cysteine residues in the relative 1-3 (Cys 58 and Cys 69) and 2-4 (Cys 64 and Cys 74) positions. Lc-LEAP2 was most abundantly expressed in the muscle, supraneural body and buccal gland of lamprey, and was significantly upregulated during LPS and Poly I:C stimulations. The mature peptide was synthesized and characterized for its antibacterial activity against different bacteria. Lc-LEAP2 possessed inhibition of a wide range of bacteria with a dose-dependence, disrupting the integrity of bacterial cell membranes and binding to bacterial genomic DNA, although its inhibitory function is weak compared to that of higher vertebrates. These data suggest that Lc-LEAP2 plays an important role in the innate immunity of lamprey and is of great value in improving resistance to pathogens. In addition, the antimicrobial mechanism of LEAP2 has been highly conserved since its emergence in primitive vertebrates., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

3D printing is now recognized as a significant tool for medical research and clinical practice, leading to the emergence of medical 3D printing technology. It is essential to improve the properties of 3D-printed products to meet the demand for medical use. The core of generating qualified 3D printing products is to develop advanced materials and processes. Taking advantage of nanomaterials with tunable and distinct physical, chemical, and biological properties, integrating nanotechnology into 3D printing creates new opportunities for advancing medical 3D printing field. Recently, some attempts are made to improve medical 3D printing through nanotechnology, providing new insights into developing advanced medical 3D printing technology. With high-resolution 3D printing technology, nano-structures can be directly fabricated for medical applications. Incorporating nanomaterials into the 3D printing material system can improve the properties of the 3D-printed medical products. At the same time, nanomaterials can be used to expand novel medical 3D printing technologies. This review introduced the strategies and progresses of improving medical 3D printing through nanotechnology and discussed challenges in clinical translation., (© 2023 Wiley-VCH GmbH.)

Acetate is a major intermediate in the anaerobic digestion of organic waste to produce CH 4 . In methanogenic systems, acetate degradation is carried out by either acetoclastic methanogenesis or syntrophic degradation by acetate oxidizers and hydrogenotrophic methanogens. Due to challenges in the isolation of syntrophic acetate-oxidizing bacteria (SAOB), the diversity and metabolism of SAOB and the mechanisms of their interactions with methanogenic partners are not fully characterized. In this study, the in situ activity and metabolic characteristics of potential SAOB and their interactions with methanogens were elucidated through metagenomics and metatranscriptomics. In addition to the reported SAOB classified in the genera Tepidanaerobacter , Desulfotomaculum , and Thermodesulfovibrio , we identified a number of potential SAOB that are affiliated with Clostridia , Thermoanaerobacteraceae, Anaerolineae, and Gemmatimonadetes. The potential SAOB possessing the glycine-mediated acetate oxidation pathway dominates SAOB communities. Moreover, formate appeared to be the main product of the acetate degradation by the most active potential SAOB. We identified the methanogen partner of these potential SAOB in the acetate-fed chemostat as Methanosarcina thermophila . The dominated potential SAOB in each chemostat had similar metabolic characteristics, even though they were in different fatty-acid-fed chemostats. These novel syntrophic lineages are prevalent and may play critical roles in thermophilic methanogenic reactors. This study expands our understanding of the phylogenetic diversity and in situ biological functions of uncultured syntrophic acetate degraders and presents novel insights into how they interact with methanogens.IMPORTANCECombining reactor operation with omics provides insights into novel uncultured syntrophic acetate degraders and how they perform in thermophilic anaerobic digesters. This improves our understanding of syntrophic acetate degradation and contributes to the background knowledge necessary to better control and optimize anaerobic digestion processes., Competing Interests: The authors declare no conflict of interest.

The mammalian testis and ovary possess special immunocompetence, which is central to provide protection against pathogens. However, the innate immune responses to immune challenges in lamprey gonads are poorly understood. In this study, we extracted RNA from testis and ovary tissues of lampreys at 0 hour, 8 hours and 17 days after lipopolysaccharides (LPS) stimulation and performed transcriptome sequencing. While the transcriptome profiles of the two tissues were different for the most part, genes LIP , LECT2 , LAL2 , GRN , ITLN , and C1q were found to be the most significantly up-regulated genes in both. Quantitative Real-time PCR (qRT-PCR) analysis confirmed that these genes were upregulated after stimulation. Furthermore, immunohistochemical staining showed that these genes in lamprey gonads are expressed in high quantities and have a specific distribution. Taken together, our results suggest that these genes could play an essential role in response of the gonads to LPS induction. This research establishes a basis for investigating the immune mechanism of vertebrate gonads and presents a fresh concept for gaining insight into the evolutionary development of jawless vertebrates.

Background: In the last few decades, the life expectancy of patients with transfusion-dependent thalassaemia (TDT) and sickle cell disease (SCD) has improved significantly, in part because of improved iron chelation. Fertility challenges and pregnancy complications have historically limited reproductive options in this group; however, improved multi-disciplinary care has made infertility a chronic disease complication requiring attention. Despite this, there are very few reports and no Australian data describing fertility and pregnancy outcomes in this population., Aims: To identify the rate of assisted reproductive technologies (ART) utilisation in our female transfusion-dependent haemoglobinopathy patients and to establish the nature of maternal and neonatal complications in this cohort., Methods: A 20-year retrospective analysis (1997-2017) at an Australian centre captured data on conception rates, use of assisted reproductive techniques (ART), and pregnancy and neonatal outcomes in female transfusion-dependent haemoglobinopathy patients., Results: Conception was attempted in 14 women (11 TDT and three SCD) during the study period. A total of 28 pregnancies resulting in 25 live births were recorded. ART supported 13 conceptions. A positive association was not identified between elevated mean serum ferritin and ART use; however, all patients with an established diagnosis of hypogonadotropic hypogonadism (HH) required ART. Maternal complications included gestational diabetes mellitus and post-partum haemorrhage. There were no cardiac complications. Two-thirds of women underwent lower segment caesarean section, with prematurity complicating 20% of births. There were no neonatal or maternal deaths., Conclusion: Pregnancy is an achievable goal for women with transfusion-dependent haemoglobinopathies, although the support of ART may be required in a subset of patients., (© 2023 Royal Australasian College of Physicians.)

The insecticide dimethoate, an organophosphate, has been used on crops, soybeans, fruits, and vegetables since the 1960s and is considered one of the most widely used pesticides. However, the understanding of the molecular mechanisms of dimethoate in crops, especially crop seedlings, is still limited. The green vegetable soya bean (Glycine max merr) is usually used as a vegetable-like fruit of soybean in many Asian countries. This study aimed to analyze the effect of dimethoate on the growth of green vegetable soya bean seedlings at the metabolic and transcriptional levels. An integrated analysis of the transcriptome and metabolome was performed to determine the responses of green vegetable soya bean seedlings to different concentrations (D1 for low dose, D2 for high dose and C for control) of dimethoate. In omics analyses, 4156 differentially expressed genes (DEGs) and 1935 differentially abundant metabolites (DAMs) were identified in the D1/C comparison, and 11,162 DEGs and 819 DAMs were identified in D2/C. Correlation analyses revealed dimethoate affected the metabolic pathways of green vegetable soya beans such as the biosynthesis of secondary metabolites and microbial metabolism in diverse environmental pathways, demonstrating that even small doses of dimethoate can affect green vegetable soya bean seedlings in a short period of time. Our study further enriches our understanding of the molecular mechanisms by which green vegetable soya beans are treated with dimethoate and provides a deeper understanding of the effects of dimethoate on crops., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Hypothesis: Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia., Study Design: Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ± 13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ± 12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio., Study Results: The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P = .009). SCZ had a significantly lower whole-brain white matter average FA (P < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r = 0.29, P = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r = -0.23, P = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P = .217) in SCZ., Conclusions: Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Key Message: A novel light-dependent dominant lesion mimic mutant with enhanced multiple disease resistance was physiologically, biochemically, and genetically characterized; the causal gene was fine mapped to a 909 kb interval containing 38 genes. Identification of genes that confer multiple disease resistance (MDR) is crucial for the improvement of maize disease resistance. However, very limited genes are identified as MDR genes in maize. In this study, we characterized a dominant disease lesion mimics 8 (Les8) mutant that had chlorotic lesions on the leaves and showed enhanced resistance to both curvularia leaf spot and southern leaf blight. Major agronomic traits were not obviously altered, while decreased chlorophyll content was observed in the mutant, and the genetic effect of the Les8 mutation was stable in different genetic backgrounds. By BSR-seq analysis and map-based cloning, the LES8 gene was mapped into a 909 kb region containing 38 candidate genes on chromosome 9 wherein no lesion mimic or disease-resistance genes were previously reported. Using transcriptomics analysis, we found that genes involved in defense responses and secondary metabolite biosynthesis were enriched in the significantly up-regulated genes, while genes involved in photosynthesis and carbohydrate-related pathways were enriched in the significantly down-regulated genes in Les8. In addition, there was an overaccumulation of jasmonic acid and lignin but not salicylic acid in Les8. Taken together, this study revealed candidate genes and potential mechanism underlying Les8-conferred MDR in maize., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The effect of microplastics (MPs) retained in waste activated sludge (WAS) on anaerobic digestion (AD) performance has attracted more and more attention. However, their effect on thermophilic AD remains unclear. Here, the influence of polyvinyl chloride (PVC) MPs on methanogenesis and active microbial communities in mesophilic (37 °C) and thermophilic (55 °C) AD was investigated. The results showed that 1, 5, and 10 mg/L PVC MPs significantly promoted the cumulative methane yield in mesophilic AD by 5.62%, 7.36%, and 8.87%, respectively, while PVC MPs reduced that in thermophilic AD by 13.30%, 18.82%, and 19.99%, respectively. Moreover, propionate accumulation was only detected at the end of thermophilic AD with PVC MPs. Microbial community analysis indicated that PVC MPs in mesophilic AD enriched hydrolytic and acidifying bacteria (Candidatus Competibacter, Lentimicrobium, Romboutsia, etc.) together with acetoclastic methanogens (Methanosarcina, Methanosaeta). By contrast, most carbohydrate-hydrolyzing bacteria, propionate-oxidizing bacterium (Pelotomaculum), and Methanosarcina were inhibited by PVC MPs in thermophilic AD. Network analysis further suggested that PVC MPs significantly changed the relationship of key microorganisms in the AD process. A stronger correlation among the above genera occurred in mesophilic AD, which may promote the methanogenic performance. These results suggested that PVC MPs affected mesophilic and thermophilic AD of WAS via changing microbial activities and interaction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)