The prevalence and its associated factors of psychological stress among middle school students in China: pooled evidence from a systematic scoping review.

Psychological issues are of significant concern in present-day society, as poor mental well-being results in depression and suicidal behavior. Understanding the current situation of psychological stress among secondary school students will help policy makers to formulate targeted measures to help them cope with stress, and at the same time evaluate the effectiveness of the existing policies to address the shortcomings and enhance the diversification of interventions. The main purpose of this review was to map the existing evidence on the prevalence and levels of psychological stress among adolescents in China, and to identify the associated risk factors. This review strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed spanning Web of Science, PubMed, and Scopus databases. Studies involving only humans and full text in English were selected. Selection was limited to samples from mainland China, Hong Kong, Macau, and Taiwan. Variables were extracted, exploring the factors that affected the mental wellness of Chinese middle school students. A final 15 articles and 1 report were included. The findings revealed psychological stress is prevalent among Chinese middle school population, with the degree of prevalence from low to severe stress levels. Three dimensions of psychological stress affecting Chinese secondary school students: school, family and lifestyle. Within the school, the factors included academic stress, peer relationships etc. Family-related factors were comprised of parent-child relationship, parents' mental health status etc. Lastly, lifestyle-related factors included poor diet, sedentary and inactivity etc. Our findings suggest that policy makers should reduce the excessive emphasis on examination results and focus on the all-round development of students, and that schools should organize a variety of extra-curricular activities to reduce students' stress. Parents should create a harmonious family atmosphere to minimize conflicts and maintain close communication with teachers. Systematic Review Registration: OSF; https://doi.org/10.17605/OSF.IO/HEFCP.

Facile Synthesis of Rigid Binuclear Manganese Complexes for Magnetic Resonance Angiography and SLC39A14-Mediated Hepatic Imaging.

Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.

Clinical significance of the lactate-to-albumin ratio on prognosis in critically ill patients with acute kidney injury.

OBJECTIVE: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). METHODS: A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis. RESULTS: A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001). CONCLUSION: High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.

The 'Candidatus phytoplasma ziziphi' effectors SJP1 and SJP2 destabilise the bifunctional regulator ZjTCP7 to modulate floral transition and shoot branching.

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11-like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT-ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7-SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies.

Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

Multifunctional Super-Hydrophilic MXene/Biomass Composite Aerogel Evaporator for Efficient Solar-Driven Desalination and Wastewater Treatment.

Solar-driven interfacial evaporation is recognized as a sustainable and effective strategy for desalination to mitigate the freshwater scarcity issue. Nevertheless, the challenges of oil contamination, salt accumulation, and poor long-term stability of the solar desalination process limit its applications. Herein, a 3D biomass-based multifunctional solar aerogel evaporator is developed for water production with fabricated chitosan/lignin (CSL) aerogel as the skeleton, encapsulated with carbonized lignin (CL) particles and Ti3C2TiX (MXene) nanosheets as light-absorbing materials. Benefitting from its super-hydrophilic wettability, interconnected macropore structure, and high broadband light absorption (ca. 95.50%), the prepared CSL-C@MXene-20 mg evaporator exhibited a high and stable water evaporation flux of 2.351 kg m-2 h-1 with an energy conversion efficiency of 88.22% under 1 Sun (1 kW m-2) illumination. The CSL-C@MXene-20 mg evaporator performed excellent salt tolerance and long-term solar vapor generation in a 3.5 wt.% NaCl solution. Also, its super-hydrophilicity and oleophobicity resulted in superior salt resistance and anti-fouling performance in high salinity brine (20 wt.% NaCl) and oily wastewater. This work offers new insight into the manufacture of porous and eco-friendly biomass-based photothermal aerogels for advanced solar-powered seawater desalination and wastewater purification.

The association between albumin-corrected calcium and prognosis in patients with cardiac arrest: a retrospective study based on the MIMIC-IV database.

BACKGROUND: Cardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA. METHODS: We retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group (< 8.86), moderate ACC group (8.86-10.32), and high ACC group (> 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan-Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results. RESULTS: Cut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P < 0.05). The Cox analyses before and after IPTW adjustment showed that both low ACC and high ACC group were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). The results obtained from sensitivity analyses indicated the stability of the findings. The Kaplan-Meier survival curves indicated that 90- and 360-day cumulative survival rates in the low ACC and high ACC groups were lower than that in the moderate ACC group (χ2 = 11.350, P = 0.003; χ2 = 14.110, P = 0.001). CONCLUSION: Both low ACC (< 8.86) and high ACC groups (> 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). For those CA patients with high and low ACC, it deserved the attention of clinicians.

Covalent Organic Framework Enhanced Solid Polymer Electrolyte for Lithium Metal Batteries.

High ionic conductivity, outstanding mechanical stability, and a wide electrochemical window are the keys to the application of solid-state lithium metal batteries (LMBs). Due to their regular channels for ion transport and tailored functional groups, covalent organic frameworks (COFs) have been applied to solid electrolytes to improve their performance. Herein, we report a flexible polyethylene oxide-COF-LZU1 (abbreviated as PEO-COF) electrolyte membrane with a high lithium ion transference number and satisfactory mechanical strength, allowing for dendrite-free and long-time cycling for LMBs. Benefiting from the interaction between bis(triflfluoromethanesulonyl)imide anions (TFSI-) and aldehyde groups in COF-LZU1, the Li+ transference number of the PEO-5% COF-LZU1 electrolyte reached up to 0.43, much higher than that of neat PEO electrolyte (0.18). Orderly channels are conducive to the homogenous Li-+ deposition, thereby inhibiting the lithium dendrites. The assembled LiFePO4|PEO-5% COF-LZU1/Li cells delivered a discharge specific capacity of 146 mAh g-1 and displayed a capacity retention of 80% after 200 cycles at 0.1 C (60 °C). The Li/Li symmetrical cells of the PEO-5% COF-LZU1 electrolyte presented a longer working stability at different current densities compared to that of the PEO electrolyte. Therefore, the enhanced comprehensive performance of the solid electrolyte shows potential application prospects for use in LMBs.

Structure and immunostimulatory activity studies on two novel Flammulina velutipes polysaccharides: revealing potential impacts of →6)-α-D-Glcp(1→ on the TLR-4/MyD88/NF-κB pathway.

Two novel Flammulina velutipes (F. velutipes) polysaccharides, FVPH1 and FVPH2, were isolated and purified after hot water extraction. The structural characterization revealed that the backbone of FVPH1 consisted mainly of →6)-α-D-Glcp(1→, →3,4)-α-D-Galp(1→, →4)-α-L-Fucp(1→, and →4)-ß-D-Manp(1→, while the backbone of FVPH2 consisted of →3)-α-D-Galp(1→, →3,4)-α-D-Manp(1→,→6)-α-D-Glcp(1→. The branches of FVPH1 contained →6)-α-D-Glcp(1→ and α-D-Glcp(1→ and the branches of FVPH2 consisted of →3)-α-D-Galp(1→, →6)-α-D-Glcp(1→, and ß-L-Fucp(1→. FVPH2 exhibited significantly better immunostimulatory activity than FVPH1 (P < 0.05), as evidenced by the increased expression of NO, IL-1ß, IL-6, and TNF-α and pinocytic activity of RAW264.7 cells. As the most abundant structure in the polysaccharides of F. velutipes, the content of →6)-α-D-Glcp(1→ might play a crucial role in influencing the immunostimulatory activity of F. velutipes polysaccharides. The F. velutipes polysaccharide with a lower content of →6)-α-D-Glcp(1→ and a higher branching degree could significantly enhance the immunostimulatory activity of F. velutipes polysaccharides via activating the TLR-4/MyD88/NF-κB pathway more effectively.

The relationship between lactate dehydrogenase to albumin ratio and all-cause mortality during ICU stays in patients with sepsis: A retrospective cohort study with propensity score matching.

Background: Sepsis is a prevalent and severe medical condition which is frequently observed in the intensive care unit (ICU). Although numerous biomarkers have been identified to predict the prognosis of sepsis, the lactate dehydrogenase to albumin ratio (LDH/ALB ratio) has not been extensively investigated. The principal objective of this study is to assess the relationship between LDH/ALB ratio and all-cause mortality in patients with sepsis. Methods: This study included all adult critically ill patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.0) database. Propensity score matching (PSM) analysis was conducted to mitigate bias, and Kaplan-Meier curves were performed to evaluate the cumulative survival across different groups. The association between the LDH/ALB ratio and mortality was examined through restricted cubic spline (RCS) analysis and Cox regression analysis. The robustness of the findings was confirmed through subgroup analyses. Additionally, the prognostic capability of the LDH/ALB ratio was further evaluated using receiver operating characteristic (ROC) curve analysis. Results: There were 6059 adult patients with sepsis enrolled in the final analysis. RCS revealed a non-linear relationship between the LDH/ALB ratio and an increased risk of ICU all-cause mortality (χ2 = 46.900, P < 0.001). Following PSM analysis, 1553 matched pairs were obtained. As comparison to the low LDH/ALB ratio group, the mortality rate in the high LDH/ALB ratio group was significantly higher (P < 0.001). Kaplan-Meier curves, both before and after PSM, revealed that the ICU cumulative survival rate for patients with sepsis was significantly lower in the high LDH/ALB ratio group compared to the low LDH/ALB ratio group (χ2 = 93.360, P < 0.001; χ2 = 14.400, P < 0.001). Even after adjusting for a range of potential confounders, multivariate Cox regression analysis indicated that an elevated LDH/ALB ratio was a significant predictor of all-cause mortality in these patients. ROC curve analysis demonstrated that the LDH/ALB ratio had an area under the ROC curve (AUC) of 0.688 for predicting ICU mortality, with a sensitivity of 69.2% and a specificity of 58.6%. Conclusions: An elevated LDH/ALB ratio (≥10.57) was associated with all-cause mortality in critically ill patients with sepsis, and it might serve as a prognostic marker. Clinicians should pay closer attention to sepsis patients presenting with an LDH/ALB ratio of 10.57 or higher.

Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach.

Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and - 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.

Interpretation of the phenolation and structural changes of lignin in a novel ternary deep eutectic solvent.

Deep eutectic solvents (DES) are promising green solvents for depolymerization and reconstruction of lignin. Revealing the transformations of lignin during DES treatment is beneficial for high potential lignin applications. In this study, bagasse lignin was treated with a binary DES and three ternary DESs, respectively. The results showed that net hydrogen bonding acidity(α-ß) value of DES was positively correlated to the increment of phenolic hydroxyl of lignin, and the ternary DES of choline chloride-formic acid-oxalic acid (ChCl-FA-OA) exhibited the best phenolation performances. The phenolic hydroxyl content of ChCl-FA-OA treated lignin was increased by 50.4 %, reaching 2.41 mmol/g under optimum conditions (120 °C, 4 h, ChCl-FA-OA = 1:2:1). Moreover, it was found that the cleavage of ß-O-4' aryl ether bond and ester bond were dominant reactions during the treatment, accompanied by condensation reactions. Additionally, the obtained lignin oil contained various syringyl and guaiacyl derived phenolic compounds. Especially, the content of acetovanillone in lignin oil reached 29.94 %, much higher than in previous studies. Finally, the degradation mechanism of lignin in ChCl-FA-OA system was proposed. The present work provided insights into the relationship between lignin phenolation and DES properties. The novel ChCl-FA-OA system can achieve efficient lignin depolymerization, and convert lignin biomass into value-added chemical products.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Analysis of heterologous expression of phaCBA promotes the acetoin stress response mechanism in Bacillus subtilis using transcriptomics and metabolomics approaches.

Acetoin, a versatile platform chemical and popular food additive, poses a challenge to the biosafety strain Bacillus subtilis when produced in high concentrations due to its intrinsic toxicity. Incorporating the PHB synthesis pathway into Bacillus subtilis 168 has been shown to significantly enhance the strain's acetoin tolerance. This study aims to elucidate the molecular mechanisms underlying the response of B. subtilis 168-phaCBA to acetoin stress, employing transcriptomic and metabolomic analyses. Acetoin stress induces fatty acid degradation and disrupts amino acid synthesis. In response, B. subtilis 168-phaCBA down-regulates genes associated with flagellum assembly and bacterial chemotaxis, while up-regulating genes related to the ABC transport system encoding amino acid transport proteins. Notably, genes coding for cysteine and D-methionine transport proteins (tcyB, tcyC and metQ) and the biotin transporter protein bioY, are up-regulated, enhancing cellular tolerance. Our findings highlight that the expression of phaCBA significantly increases the ratio of long-chain unsaturated fatty acids and modulates intracellular concentrations of amino acids, including L-tryptophan, L-tyrosine, L-leucine, L-threonine, L-methionine, L-glutamic acid, L-proline, D-phenylalanine, L-arginine, and membrane fatty acids, thereby imparting acetoin tolerance. Furthermore, the supplementation with specific exogenous amino acids (L-alanine, L-proline, L-cysteine, L-arginine, L-glutamic acid, and L-isoleucine) alleviates acetoin's detrimental effects on the bacterium. Simultaneously, the introduction of phaCBA into the acetoin-producing strain BS03 addressed the issue of insufficient intracellular cofactors in the fermentation strain, resulting in the successful production of 70.14 g/L of acetoin through fed-batch fermentation. This study enhances our understanding of Bacillus's cellular response to acetoin-induced stress and provides valuable insights for the development of acetoin-resistant Bacillus strains.

SETDB1: Progress and prospects in cancer treatment potential and inhibitor research.

SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.

Improved bioavailability and antioxidation of ß-carotene-loaded biopolymeric nanoparticles stabilized by glycosylated oat protein isolate.

The limited bioavailability of ß-carotene hinders its potential application in functional foods, despite its excellent antioxidant properties. Protein-based nanoparticles have been widely used for the delivery of ß-carotene to overcome this limitation. However, these nanoparticles are susceptible to environmental stress. In this study, we utilized glycosylated oat protein isolate to prepare nanoparticles loaded with ß-carotene through the emulsification-evaporation method, aiming to address this challenge. The results showed that ß-carotene was embedded into the spherical nanoparticles, exhibiting relatively high encapsulation efficiency (86.21 %) and loading capacity (5.43 %). The stability of the nanoparticles loaded with ß-carotene was enhanced in acidic environments and under high ionic strength. The nanoparticles offered protection to ß-carotene against gastric digestion and facilitated its controlled release (95.76 % within 6 h) in the small intestine, thereby leading to an improved in vitro bioavailability (65.06 %) of ß-carotene. This improvement conferred the benefits on ß-carotene nanoparticles to alleviate tert-butyl hydroperoxide-induced oxidative stress through the upregulation of heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1 expression, as well as the promotion of nuclear translocation of nuclear factor-erythroid 2-related factor 2. Our study suggests the potential for the industry application of nanoparticles based on glycosylated proteins to effectively deliver hydrophobic nutrients and enhance their application.