Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

AhR agonists screening and identification in indoor dust based on non-target chemical analysis by GC-Q-TOFMS and biological effect evaluation referring to ToxCast/Tox21 database.

Numerous studies reported the concentration of agonists of aryl hydrocarbon receptor (AhR) in indoor dust by target chemical analysis or the biological effects of activating the AhR by indoor extracts, but the major AhR agonists identification in indoor dust were rarely researched. In the present study, the indoor dust samples were collected for 7-ethoxyresorufin O-deethylase (EROD) assay and both non-targeted and targeted chemical analysis for AhR agonists by gas chromatography quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry analysis. Coupled with non-targeted analysis and toxicity Forecaster (ToxCast)/Tox21 database, 104 ToxCast chemicals were screened to be able to induce EROD response. The combination of targeted chemical analyses and biological effects evaluation indicated that PAHs, dibutyl phthalate (DBP) and Cypermethrin might be the important AhR-agonists in different indoor dust and mainly contributed in 1.84% to 97.56 % (median: 26.62%) of total observed biological effects through comparing toxic equivalency quotient derived from chemical analysis with biological equivalences derived from bioassay. DBP and cypermethrin seldom reported in the analysis of AhR agonists should raise great concern. In addition, the present results in experiment of synthetic solution of 4 selected AhR-agonists pointed out that some unidentified AhR agonists existed in indoor dust.

The potential crosstalk genes and molecular mechanisms between glioblastoma and periodontitis.

Despite clinical and epidemiological evidence suggestive of a link between glioblastoma (GBM) and periodontitis (PD), the shared mechanisms of gene regulation remain elusive. In this study, we identify differentially expressed genes (DEGs) that overlap between the GEO datasets GSE4290 [GBM] and GSE10334 [PD]. Functional enrichment analysis was conducted, and key modules were identified using protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). The expression levels of CXCR4, LY96, and C3 were found to be significantly elevated in both the test dataset and external validation dataset, making them key crosstalk genes. Additionally, immune cell landscape analysis revealed elevated expression levels of multiple immune cells in GBM and PD compared to controls, with the key crosstalk genes negatively associated with Macrophages M2. FLI1 was identified as a potential key transcription factor (TF) regulating the three key crosstalk genes, with increased expression in the full dataset. These findings contribute to our understanding of the immune and inflammatory aspects of the comorbidity mechanism between GBM and PD.

Electricity generation from carbon dioxide adsorption by spatially nanoconfined ion separation.

Selective ion transport underpins fundamental biological processes for efficient energy conversion and signal propagation. Mimicking these 'ionics' in synthetic nanofluidic channels has been increasingly promising for realizing self-sustained systems by harvesting clean energy from diverse environments, such as light, moisture, salinity gradient, etc. Here, we report a spatially nanoconfined ion separation strategy that enables harvesting electricity from CO2 adsorption. This breakthrough relies on the development of Nanosheet-Agarose Hydrogel (NAH) composite-based generators, wherein the oppositely charged ions are released in water-filled hydrogel channels upon adsorbing CO2. By tuning the ion size and ion-channel interactions, the released cations at the hundred-nanometer scale are spatially confined within the hydrogel network, while ångström-scale anions pass through unhindered. This leads to near-perfect anion/cation separation across the generator with a selectivity (D-/D+) of up to 1.8 × 106, allowing conversion into external electricity. With amplification by connecting multiple as-designed generators, the ion separation-induced electricity reaching 5 V is used to power electronic devices. This study introduces an effective spatial nanoconfinement strategy for widely demanded high-precision ion separation, encouraging a carbon-negative technique with simultaneous CO2 adsorption and energy generation.

Constricted posterior fourchette deformities: Definition, classification and surgical treatments.

BACKGROUND: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. METHODS: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y-V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. RESULTS: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y-V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. CONCLUSION: Constricted posterior fourchette seriously affects the quality of life. Y-V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

Current insight into the transient X-zone in the adrenal gland cortex.

Mouse models have been widely used in the study of adrenal gland development and diseases. The X-zone is a unique structure of the mouse adrenal gland and lineage-tracing studies show that the X-zone is a remnant of the fetal adrenal cortex. Although the X-zone is considered analogous to the fetal zone in the human adrenal cortex, the functional significance of the X-zone has remained comparatively more obscure. The X-zone forms during the early postnatal stages of adrenal development and regresses later in a remarkable sexually dimorphic fashion. The formation and regression of the X-zone can be different in mice with different genetic backgrounds. Mouse models with gene mutations, hormone/chemical treatments, and/or gonadectomy can also display an aberrant development of the X-zone or alternatively a dysregulated X-zone regression. These models have shed light on the molecular mechanisms regulating the development and regression of these unique adrenocortical cells. This review paper briefly describes the development of the adrenal gland including the formation and regression processes of the X-zone. It also summarizes and lists mouse models that demonstrate different X-zone phenotypes.

Comprehensive aesthetic corrections of gynecomastia using the reproducible safe and minimally invasive surgical strategy.

BACKGROUND: Minimally invasive access and fast recovery are trends of gynecomastia surgery. We placed great importance on liposuction and modified original pull-through technique. The purpose of this study was to present a refined surgical strategy for gynecomastia in grade I and II. METHODS: The refined strategy embraced enhanced liposuction to remove the intraglandular fat sufficiently, followed by open resection of gland using the pull-through and bottom-up technique with adjuvant liposuction in the end. Surgical data were recorded and satisfactory questionnaires with 5-point scales were administered during follow-up. RESULTS: Between January 2017 and May 2022, 165 patients underwent enhanced liposuction combined with the pull-through and bottom-up technique for gland excision. Age ranged from 12 to 56 years. The median length of surgery was 100 min. A median of 300 ml of fat was aspirated and a median of 20.8 g of gland was excised. Seventy-seven patients (46.7%) responded the questionnaires at least 6 months postoperatively, and the average overall satisfaction was 4.68 ± 0.52 points. Thirteen sides of breasts developed complications with a rate of 4.0%. CONCLUSION: Enhanced liposuction combined with pull-through and bottom-up technique proved effective to treat grade I and II gynecomastia with minimal scarring and high satisfaction. The refined strategy was simple and safe, and would obtain optimal outcomes even for inexperienced surgeons.

Deep eutectic solvent-infused two-dimensional metal-organic framework membranes as quasi-solid-state electrolytes for wearable micro-supercapacitors.

The burgeoning field of miniaturized and portable electronic devices calls for novel advances in micro-energy storage technology. Micro-supercapacitors (MSC) stand at the forefront of this endeavour, yet unlocking their full potential necessitates the exploration of high-performance electrolytes. Herein, we introduce a strategy that leverages flexible metal-organic framework (MOF, CuTCPP) nanosheet-based membranes to construct quasi-solid-state electrolytes (QSSEs) and enhance the ionic conductivity and electrochemical performance of deep eutectic solvent (DES)-based MSCs. Owing to the multiple nanochannel pathways provided by the porous MOF nanosheets, the ionic conductivity of DES within the nanochannels exhibits a 13-fold increment compared with its bulk counterpart. Furthermore, we engineered MSC harnessing the CuTCPP-DES system, whose performance surpasses that reported for most of the ionic liquid and 2D material-based MSCs. The areal-specific capacitance was 81.3 mF cm-2 at a current density of 0.1 mA cm-2, and the energy density was 45.17 µW h cm-2 at a power density of 8.559 mW cm-2. Notably, the performance of MSCs remains consistent and unaffected, even when subjected to bending. These findings contribute to the exploration and potential optimization of the inherent benefits of MOFs, thereby presenting a paradigm shift in nanoconfined systems for microscale energy storage applications.

Cross-linking electrospinning.

Although electrospinning (e-spinning) has witnessed rapid development in recent years, it has also been criticized by environmentalists due to the use of organic solvents. Therefore, aqueous e-spinning (green e-spinning) is considered a more attractive technique. However, considering the poor water resistance and mechanical properties of electrospun (e-spun) nanofibers, cross-linking is a perfect solution. In this review, we systematically discuss the cross-linking e-spinning system for the first time, including cross-linking strategies (in situ, liquid immersion, vapor, and spray cross-linking), cross-linking mechanism (physical and chemical cross-linking) of e-spun nanofibers, and the various applications (e.g., tissue engineering, drug delivery, water treatment, food packaging, and sensors) of cross-linked e-spun nanofibers. Among them, we highlight several cross-linking methods, including UV light cross-linking, electron beam cross-linking, glutaraldehyde (and other commonly used cross-linking agents) chemical cross-linking, thermal cross-linking, and enzymatic cross-linking. Finally, we confirm the significance of cross-linking e-spinning and reveal the problems in the construction of this system.

Two-dimensional MXene membranes with biomimetic sub-nanochannels for enhanced cation sieving.

Membranes with high ion permeability and selectivity are of considerable interest for sustainable water treatment, resource extraction and energy storage. Herein, inspired by K+ channel of streptomyces A (KcsA K+), we have constructed cation sieving membranes using MXene nanosheets and Ethylenediaminetetraacetic acid (EDTA) molecules as building blocks. Numerous negatively charged oxygen atoms of EDTA molecules and 6.0 Å two-dimensional (2D) sub-nanochannel of MXene nanosheets enable biomimetic channel size, chemical groups and tunable charge density for the resulting membranes. The membranes show the capability to recognize monovalent/divalent cations, achieving excellent K+/Mg2+ selectivity of 121.2 using mixed salt solution as the feed, which outperforms other reported membranes under similar testing conditions and transcends the current upper limit. Characterization and simulations indicate that the cation recognition effect of EDTA and partial dehydration effects play critical roles in cations selective sieving and increasing the local charge density within the sub-nanochannel significantly improves cation selectivity. Our findings provide a theoretical basis for ions transport in sub-nanochannels and an alternative strategy for design ions separation membranes.

Nanoconfinement enabled non-covalently decorated MXene membranes for ion-sieving.

Covalent modification is commonly used to tune the channel size and functionality of 2D membranes. However, common synthesis strategies used to produce such modifications are known to disrupt the structure of the membranes. Herein, we report less intrusive yet equally effective non-covalent modifications on Ti3C2Tx MXene membranes by a solvent treatment, where the channels are robustly decorated by protic solvents via hydrogen bond network. The densely functionalized (-O, -F, -OH) Ti3C2Tx channel allows multiple hydrogen bond establishment and its sub-1-nm size induces a nanoconfinement effect to greatly strengthen these interactions by maintaining solvent-MXene distance and solvent orientation. In sub-1-nm ion sieving and separation, as-decorated membranes exhibit stable ion rejection, and proton-cation (H+/Mn+) selectivity that is up to 50 times and 30 times, respectively, higher than that of pristine membranes. It demonstrates the feasibility of non-covalent methods as a broad modification alternative for nanochannels integrated in energy-, resource- and environment-related applications.

Lc-pPG-612-OmpU-CTB: A promising oral vaccine for protecting Carassius auratus against Vibrio mimicus infection.

Vibrio mimicus (V. mimicus) is known to cause severe bacterial diseases with high mortality rates in fish, resulting in significant economic losses in the global aquaculture industry. Therefore, the objective of this study was to develop a safe and effective vaccine for protecting Carassius auratus (C. auratus) against V. mimicus infection. Recombinant Lactobacillus casei (L. casei) strains, Lc-pPG-612-OmpU and Lc-pPG-612-OmpU-CTB (surface-displayed), were constructed using a L. casei strain (ATCC 393) as an antigen delivery carrier and the cholera toxin B subunit (CTB) as an adjuvant. The two recombinant strains of L. casei were administered to C. auratus via oral immunization, and the protective efficacy of the oral vaccines was assessed. The results demonstrated that oral immunization with the two strains significantly increased the levels of nonspecific immune indicators in C. auratus, including alkaline phosphatase (AKP), lysozyme (LYS), acid phosphatase (ACP), complement 3 (C3), complement 4 (C4), lectin, and superoxide dismutase (SOD). Moreover, the experiment groups exhibited significant increases in specific immunoglobulin M (IgM) antibodies against OmpU, as well as the transcription of immune-related genes (ie., IL-1ß, TNF-α, IL-10, and TGF-ß), when compared to the control groups. Following infection of C. auratus with V. mimicus, the mortality rate of the recombinant L. casei-treated fish was observed to be lower compared to the control group. This finding suggests that recombinant L. casei demonstrates effective protection against V. mimicus infection in C. auratus. Furthermore, the addition of the immune adjuvant CTB was found to induce a more robust adaptive and innate immune response in C. auratus, resulting in reduced mortality after infection with V. mimicus.

Efficacy of a recombinant Lactobacillus plantarum Lp-pPG-Malt as an oral vaccine candidate against Aeromonas hydrophila infection in crucian carp.

Aeromonas hydrophila (A. hydrophila), a gram-negative bacterium, causes serious diseases with various clinical symptoms in farm raised fish. Thus, different ways to prevent and control A. hydrophila infection need to be explored, including a vaccine. In this study, we evaluated the protective efficacy of an oral vaccine prepared from the A. hydrophila TPS maltoporin (Malt) with Lactobacillus plantarum (L. plantarum) against A. hydrophila infection in crucian carp (Carassius auratus). For the in vivo experiment, the oral vaccine was administered to crucian carp by feeding them fish diets containing Lp-pPG-Malt, Lp-pPG and PBS for 28 days. The enzyme-linked immunosorbent assay (ELISA), leukocyte phagocytosis assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to measure the protective efficacy of the Lp-pPG-Malt. ELISA and leukocyte phagocytosis assay confirmed that Lp-pPG-Malt significantly enhanced the IgM level and nonspecific immune response of crucian carp compared with the control groups (Lp-pPG and PBS). The RT-qPCR results showed that the Lp-pPG-Malt increased the relative expression of immune-related genes (IL-10, IL-1ß, TNF-α, IFN-γ) of crucian carp in various tissues (liver, spleen, head kidney and hind intestine). Moreover, Lp-pPG-Malt significantly increased the relative percent survival of fish after intraperitoneal injection with A. hydrophila (55%) compared with the Lp-pPG and PBS groups (0%). These findings suggest that Lp-pPG-Malt can serve as an oral vaccine candidate for A. hydrophila infection and that Malt can be used as an effective antigen in crucian carp farming.

Relationship between BUN/Cr and Prognosis of HF Across the Full Spectrum of Ejection Fraction. / Relação entre a Razão Nitrogênio Ureico/Creatinina e Prognóstico de Insuficiência Cardíaca em Todo o Espectro da Fração de Ejeção.

BACKGROUND: In patients with heart failure (HF), due to the relative deficiency of blood volume, neurohormone system activation leads to renal vasoconstriction, which affects the content of blood urea nitrogen (BUN) and creatinine (Cr) in the body, while BUN and Cr are easily affected by other factors. Therefore, BUN/Cr can be used as another marker for the prognosis of HF. OBJECTIVE: Explore the prognosis of adverse outcome of HF in the high BUN/Cr group compared with the low BUN/Cr group across the full spectrum of ejection fraction. METHODS: From 2014 to 2016, symptomatic hospitalized HF patients were recruited and followed up to observe adverse cardiovascular outcomes. Logistic analysis and COX analysis were performed to determine significance. p-values <0.05 were considered statistically significant. RESULTS: In the univariate logistic regression analysis, the high BUN/Cr group had a higher risk of adverse outcome in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Multivariate logistic regression analysis showed that the risk of cardiac death in the HFrEF group was higher than that in the low BUN/Cr group, while the risk of all-cause death was significant only in 3 months (p<0.05) (Central Illustration). The risk of all-cause death in the high BUN/Cr in the HFpEF group was significantly higher than that in the low BUN/Cr group at two years. CONCLUSION: The high BUN/Cr group is related to the risk of poor prognosis of HFpEF, and is not lower than the predictive value of left ventricular ejection fraction (LVEF).

FUNDAMENTO: Em pacientes com insuficiência cardíaca (IC), devido à relativa deficiência do volume sanguíneo, a ativação do sistema neuro-hormonal leva à vasoconstrição renal, que afeta o teor de nitrogênio ureico (NU) e creatinina (C) no organismo, sendo que NU e C são facilmente afetados por outros fatores. Portanto, a razão NU/C pode ser utilizada como mais um marcador para o prognóstico da IC. OBJETIVO: Explorar o prognóstico do desfecho adverso da IC no grupo NU/C alta em comparação com o grupo NU/C baixa em todo o espectro da fração de ejeção. MÉTODOS: De 2014 a 2016, pacientes sintomáticos hospitalizados com IC foram recrutados e acompanhados para observar desfechos cardiovasculares adversos. Foram realizadas análise logística e a análise COX para determinar a significância. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: Na análise de regressão logística univariada, o grupo NU/C alta apresentou maior risco de desfecho adverso na insuficiência cardíaca com fração de ejeção reduzida (ICFEr) e insuficiência cardíaca com fração de ejeção preservada (ICFEp). A análise de regressão logística multivariada mostrou que o risco de morte cardíaca no grupo ICFEr foi maior do que no grupo NU/C baixa, enquanto o risco de morte por todas as causas foi significativo apenas em 3 meses (p<0,05) (Ilustração Central). O risco de morte por todas as causas no grupo NU/C alta no grupo ICFEP foi significativamente maior do que no grupo NU/C baixa em dois anos. CONCLUSÃO: O grupo NU/C alta está relacionado ao risco de mau prognóstico da ICFEP, não sendo inferior ao valor preditivo da fração de ejeção do ventrículo esquerdo (FEVE).

Bupleurum chinense exerts a mild antipyretic effect on LPS-induced pyrexia rats involving inhibition of peripheral TNF-α production.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix, the dried roots of Bupleurum chinense DC. (BC) or Bupleurum scorzonerifolium Willd., is one of the most frequently used traditional Chinese medicines. As the species in Xiao-Chai-Hu decoction, BC has been used as an antipyretic medicine with a long history. However, its antipyretic characteristics and underlying mechanism(s) remain unclear. AIM OF THE STUDY: To elucidate the antipyretic characteristics and mechanism(s) of BC used in its traditional way. METHODS: The water extract of BC (BCE) was prepared according to the traditional decocting mode. Murine fever and endotoxemia models were induced by intravenous injection of lipopolysaccharide (LPS). In vitro complement activation assay and the levels of TNF-α, IL-6, IL-1ß, and C5a were determined by ELISA. RESULTS: BCE exerted a confirmed but mild antipyretic effect on LPS-induced fever of rat. In vitro, it significantly lowered LPS-elevated TNF-α in the supernatant of rat complete blood cells and THP-1 cells, but failed to decrease IL-6 and IL-1ß. In murine endotoxemia models, BCE markedly decreased serum TNF-α, but had no impact on IL-6 and IL-1ß. BCE also restricted complement activation in vitro and in vivo. Nevertheless, the mixture of saikosaponin A and D could not suppress supernatant TNF-α of monocytes and serum TNF-α of endotoxemia mice. CONCLUSIONS: The present study dissects the peripheral mechanism for the antipyretic effect of BC used in the traditional way. Our findings indicate that BCE directly suppresses monocyte-produced TNF-α, thus decreasing circulating TNF-α, which may be responsible for its mild but confirmed antipyretic action.

Effect of different blood pressure levels on short-term outcomes in hospitalized heart failure patients.

Background: To investigate the influence of blood pressure (BP) level on short-term prognosis of heart failure (HF), the effect of the BP level on clinical end point events 3 months after discharge was observed. Methods: A retrospective cohort study was performed on 1492 hospitalized HF patients. All patients were divided according to systolic blood pressure (SBP) per 20 mmHg and diastolic blood pressure (DBP) per 10 mmHg. Logistic regression analysis was used to analyze the relationship between BP level and heart failure rehospitalization, cardiac death, all-cause death and a composite end point of heart failure rehospitalization/all-cause death at 3 month follow-up after discharge. Results: After multivariable adjustment, the relationship between SBP and DBP levels and outcomes followed an inverted J curve relationship. Compared with the reference group (110 < SBP≤130 mmHg), the risk of all end point events significantly increased in the SBP≤90 mmHg group included heart failure rehospitalization (OR 8.16, 95%CI 2.88-23.11, P < 0.001), cardiac death (OR 5.43, 95%CI 1.97-14.96, P = 0.001), all-cause death (OR 4.85, 95%CI 1.76-13.36, P = 0.002), and composite end point (OR 2.76, 95%CI 1.03-7.41, P = 0.044). SBP>150 mmHg significantly increased the risk of heart failure rehospitalization (OR 2.67, 95%CI 1.15-6.18, P = 0.022). Compared with.the reference group (65 < DBP≤75 mmHg), cardiac death (OR 2.64, 95%CI 1.15-6.05, P = 0.022) and all-cause death (OR 2.67, 95%CI 1.20-5.93, P = 0.016) was significantly increased in DBP≤55 mmHg group. There was no significant difference among subgroups according to left ventricular ejection fraction (P > 0.05). Conclusions: There is a significant difference in the short-term prognosis 3 months after discharge in HF patients with different BP levels at discharge. There was an inverted J curve relationship between BP levels and prognosis.

Oral vaccination with recombinant Lactobacillus casei with surface displayed OmpK fused to CTB as an adjuvant against Vibrio mimicus infection in Carassius auratus.

Vibrio mimicus (V. mimicus) is a pathogenic bacterium that causes diseases in humans and various aquatic animals. A particularly efficient way to provide protection against V. mimicus is through vaccination. However, there are few commercial vaccines against V. mimics, especially oral vaccines. In our study, two surface-display recombinant Lactobacillus casei (L. casei) Lc-pPG-OmpK and Lc-pPG-OmpK-CTB were constructed using L. casei ATCC393 as an antigen delivery vector, outer membrane protein K (OmpK) of V. mimicus as an antigen, and cholera toxin B subunit (CTB) as a molecular adjuvant; furthermore, the immunological effects of recombinant L.casei in Carassius auratus (C. auratus) were assessed. The results indicated that oral recombinant L.casei Lc-pPG-OmpK and Lc-pPG-OmpK-CTB stimulated higher levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), lysozyme (LYS), lectin, C3, and C4 in C. auratus, compared with control groups (Lc-pPG group and PBS group). Furthermore, the expression of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-ß (TGF-ß) in the liver, spleen, head kidney, hind intestine and gills of C. auratus was significantly increased, compared with that in the controls. These results demonstrated that the two recombinant L. casei strains could effectively trigger humoral and cellular immunity in C. auratus. In addition, two recombinant L.casei strains were able to survive and colonize the intestine of C. auratus. Importantly, after being challenged with V. mimicus, C. auratus fed Lc-pPG-OmpK and Lc-pPG-OmpK-CTB exhibited greater survival rates than the controls (52.08% and 58.33%, respectively). The data showed that recombinant L. casei could elicit a protective immunological response in C. auratus. The effect of the Lc-pPG-OmpK-CTB group was better than that of the Lc-pPG-OmpK group, and Lc-pPG-OmpK-CTB was found to be an effective candidate for oral vaccination.

Inhalation bioacessibility and lung cell penetration of indoor PM2.5-bound PAEs and its implication in risk assessment.

Several studies have evaluated the human exposure of phthalate esters (PAEs) in PM2.5 via inhalation route, however, inhalation bioaccessibility and the lung cell penetration of PAEs were barely considered in risk assessment. In the present study, PM2.5 samples collected from indoor environments were investigated for inhalation bioaccessibility of PAEs using two simulated lung fluids (gamble's solution (GMB) and artificial lysosomal fluid (ALF)). The results showed that the inhalation bioaccessibility of PAEs (except for diethyl phthalate) under healthy state (GMB: 8.9%-62.8%) was lower than that under the inflammatory condition (ALF: 14.5%-67.6%). Lung cell permeation and metabolism of three selected PAEs (diethyl phthalate, di(n-butyl)phthalate and di-2-ethylhexyl phthalate) was tested using equivalent lung cell (A549) model. The inhalation bioavailability obtained by combination of the bioaccessibility of PAEs in indoor PM2.5 and permeability data of A549 cell ranged from 11.7% to 51.1% in health condition, and 13.5%-55.0% in inflammatory state. The calibration parameter (Fc) based on the inhalation bioavailability was established in present study and could provide a reference for a more accurate risk assessment of PM2.5-bound PAEs.

Gut Microbiota and Metabolites May Play a Crucial Role in Sea Cucumber Apostichopus japonicus Aestivation.

The constant increase in temperatures under global warming has led to a prolonged aestivation period for Apostichopus japonicus, resulting in considerable losses in production and economic benefits. However, the specific mechanism of aestivation has not been fully elucidated. In this study, we first tried to illustrate the biological mechanisms of aestivation from the perspective of the gut microbiota and metabolites. Significant differences were found in the gut microbiota of aestivating adult A. japonicus (AAJSD group) compared with nonaestivating adult A. japonicus (AAJRT group) and young A. japonicus (YAJRT and YAJSD groups) based on 16S rRNA gene high-throughput sequencing analysis. The abundances of Desulfobacterota, Myxococcota, Bdellovibrionota, and Firmicutes (4 phyla) in the AAJSD group significantly increased. Moreover, the levels of Pseudoalteromonas, Fusibacter, Labilibacter, Litorilituus, Flammeovirga, Polaribacter, Ferrimonas, PB19, and Blfdi19 genera were significantly higher in the AAJSD group than in the other three groups. Further analysis of the LDA effect size showed that species with significant variation in abundance in the AAJSD group, including the phylum Firmicutes and the genera Litorilituus, Fusibacter, and Abilibacter, might be important biomarkers for aestivating adult A. japonicus. In addition, the results of metabolomics analysis showed that there were three distinct metabolic pathways, namely biosynthesis of secondary metabolites, tryptophan metabolism, and sesquiterpenoid and triterpenoid biosynthesis in the AAJSD group compared with the other three groups. Notably, 5-hydroxytryptophan was significantly upregulated in the AAJSD group in the tryptophan metabolism pathway. Moreover, the genera Labilibacter, Litorilituus, Ferrimonas, Flammeovirga, Blfdi19, Fusibacter, Pseudoalteromonas, and PB19 with high abundance in the gut of aestivating adult A. japonicus were positively correlated with the metabolite 5-HTP. These findings suggest that there may be potential biological associations among the gut microbiota, metabolites, and aestivation in A. japonicus. This work may provide a new perspective for further understanding the aestivation mechanism of A. japonicus.