Study of the Epidemiological and Mechanistic Differences Between Carbapenem-Resistant Klebsiella pneumoniae Infections in Children and Adults.

Background: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP's epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures. Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis. Results: Infants (0-1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were bla NDM-5 in children (58.1%) and bla KPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 bla KPC-2 and ST15 bla OXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing bla NDM-5 and bla OXA-181 in the NICU. Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.

Identification of immune- and oxidative stress-related signature genes as potential targets for mRNA vaccines for pancreatic cancer patients.

Adenocarcinoma of the pancreas (PAAD) is one of the deadliest malignant tumors, and messenger ribonucleic acid vaccines, which constitute the latest generation of vaccine technology, are expected to lead to new ideas for the treatment of pancreatic cancer. The Cancer Genome Atlas-PAAD and Genotype-Tissue Expression data were merged and analyzed. Weighted gene coexpression network analysis was used to identify gene modules associated with tumor mutational burden among the genes related to both immunity and oxidative stress. Differentially expressed immune-related oxidative stress genes were screened via univariate Cox regression analysis, and these genes were analyzed via nonnegative matrix factorization. After immune infiltration analysis, least absolute shrinkage and selection operator regression combined with Cox regression was used to construct the model, and the usefulness of the model was predicted based on the receiver operating characteristic curve and decision curve analysis curves after model construction. Finally, metabolic pathway enrichment was analyzed using gene set enrichment analysis combined with Kyoto Encyclopedia of Genes and Genomes and gene ontology biological process analyses. This model consisting of the ERAP2, mesenchymal-epithelial transition factor (MET), CXCL9, and angiotensinogen (AGT) genes can be used to help predict the prognosis of pancreatic cancer patients more accurately than existing models. ERAP2 is involved in immune activation and is important in cancer immune evasion. MET binds to hepatocyte growth factor, leading to the dimerization and phosphorylation of c-MET. This activates various signaling pathways, including MAPK and PI3K, to regulate the proliferation, invasion, and migration of cancer cells. CXCL9 overexpression is associated with a poor patient prognosis and reduces the number of CD8 + cytotoxic T lymphocytes in the PAAD tumor microenvironment. AGT is cleaved by the renin enzyme to produce angiotensin 1, and AGT-converting enzyme cleaves angiotensin 1 to produce angiotensin 2. Exposure to AGT-converting enzyme inhibitors after pancreatic cancer diagnosis is associated with improved survival. The 4 genes identified in the present study - ERAP2, MET, CXCL9, and AGT - are expected to serve as targets for messenger ribonucleic acid vaccine development and need to be further investigated in depth.

Mechanisms of exacerbation of Th2-mediated eosinophilic allergic asthma induced by plastic pollution derivatives (PPD): A molecular toxicological study involving lung cell ferroptosis and metabolomics.

Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. To investigate the effects of PPD exposure on the risk of allergic asthma, we established a PPD exposure group in a mouse model. The dose administered for PS-MP was 0.1 mg/d and for DBP was 30 mg/kg/d, with a 5-week oral administration period. The pathological changes of airway tissue and the increase of oxidative stress and inflammatory response confirmed that PPD aggravated eosinophilic allergic asthma in mice. The mitochondrial morphological changes and metabolomics of mice confirmed that ferrotosis and oxidative stress played key roles in this process. Treatment with 100 mg/Kg deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological. Our findings suggest that the increased levels of reactive oxygen species (ROS) in the lungs lead to Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-5, and eosinophils, and reduced INF-γ levels. This inflammatory response is mediated by the NFκB pathway and exacerbates type I hypersensitivity through increased IL-4 production. In this study, the molecular mechanism by which PPD aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PPD and lays a theoretical foundation for addressing the health risks posed by PPD.

High-intensity interval training improves hypothalamic inflammation by suppressing HIF-1α signaling in microglia of male C57BL/6J mice.

Repeated bouts of high-intensity interval training (HIIT) induce an improvement in metabolism via plasticity of melanocortin circuits and attenuated hypothalamic inflammation. HIF-1α, which plays a vital role in hypothalamus-mediated regulation of peripheral metabolism, is enhanced in the hypothalamus by HIIT. This study aimed to investigate the effects of HIIT on hypothalamic HIF-1α expression and peripheral metabolism in obese mice and the underlying molecular mechanisms. By using a high-fat diet (HFD)-induced obesity mouse model, we determined the effect of HIIT on energy balance and the expression of the hypothalamic appetite-regulating neuropeptides, POMC and NPY. Moreover, hypothalamic HIF-1α signaling and its downstream glycolytic enzymes were explored after HIIT intervention. The state of microglia and microglial NF-κB signaling in the hypothalamus were also examined in vivo. In vitro by using an adenovirus carrying shRNA-HIF1ß, we explored the impact of HIF-1 signaling on glycolysis and NF-κB inflammatory signaling in BV2 cells. Food intake was suppressed and whole-body metabolism was improved in exercised DIO mice, accompanied by changes in the expression of POMC and NPY. Moreover, total and microglial HIF-1α signaling were obviously attenuated in the hypothalamus, consistent with the decreased levels of glycolytic enzymes. Both HFD-induced microglial activation and hypothalamic NF-κB signaling were significantly suppressed following HIIT in vivo. In BV2 cells, after HIF-1 complex knockdown, glycolysis and NF-κB inflammatory signaling were significantly attenuated. The data indicate that HIIT improves peripheral metabolism probably via attenuated HFD-induced microglial activation and microglial NF-κB signaling in the hypothalamus, which could be mediated by suppressed microglial HIF-1α signaling.

Association of alkylphenols exposure with serum liver function markers in pregnant women in Guangxi, China.

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Integrating network pharmacology and experimental models to investigate the mechanisms of XCHD and YCSLS in preventing HUA progression via TLR4/MYD88/NF-κB signaling.

With the alterations in dietary structure and the augmentation of the human living standard, hyperuricemia (HUA) has emerged as a significant factor impacting contemporary human health. It has also been scientifically validated as an independent risk determinant for the progression of renal disease. Existing literature indicates that XCHD (Xiao Chai Hu Decoction) and YCSLS (Yinchen Siling San) possess a capability to ameliorate UA levels and fortify renal function, yet a comprehensive understanding of their mechanisms of action remains elusive. This investigation is designed to elucidate the therapeutic efficacy and mechanistic underpinnings of XCHD/YCSLS on the renal tissues of HUA-afflicted rats, with the objective of fortifying the evidence base to advocate its clinical application. Our preliminary findings substantiated that XCHD and YCSLS impede HUA progression through the inhibition of inflammatory and oxidative stress pathways. Further, we synthesized data from publicly accessible repositories to forecast interactions between XCHD, YCSLS, and their prospective targets in HUA, including the associated signaling pathways. This approach facilitated the identification of shared targets of XCHD/YCSLS, and HUA, and the subsequent correlation analysis of these targets employing KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) methodologies. The findings indicate that the TLR4/MYD88/NF-κB signaling constitutes one of the potential crucial conduits engaged in XCHD and YCSLS-induced HUA mitigation. In conclusion, the analysis of WB and IHC from HUA rat models corroborated that XCHD and YCSLS do indeed attenuate the expression of TLR4/MYD88/NF-κB, reinforcing the hypothesized pivotal role of the its signaling cascade in HUA. This warrants subsequent scholarly exploration.

HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

microRNA-3037 targeting CYP6CY2 confers imidacloprid resistance to Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

Controllable Construction of a Mo2C/MoO2 Interface with an Ideal Mo2C/MoO2 Ratio for Efficient Electrocatalytic Nitrogen Reduction to Ammonia.

Electrocatalytic nitrogen reduction reaction (NRR) is considered to be a viable contender for the production of NH3. However, due to the sluggish adsorption and activation of the electrocatalyst toward inert N2 molecules, there is an urgent need for developing effective catalysts to facilitate the reaction. Inspired by natural nitrogenase, in which Mo atoms are the active centers, Mo-based electrocatalysts have received considerable attention, but further exploration is still necessary. Interface-engineered electrocatalysts can effectively optimize the absorption and activation of the catalytic active center for N2 and thus improve the electrocatalytic activity of NRR. However, the lack of studies for controllably constructing an optimal ratio of two phases at the interface hinders the development of NRR electrocatalysts. Herein, a series of Mo2C/MoO2 interface-engineered electrocatalysts with various Mo2C/MoO2 ratios were constructed by controlling the Y dosages. The controlled experimental results verified that the catalytic activity of NRR, the dosage of Y, and the ratio of Mo2C/MoO2 were strongly correlated. Density functional theory calculations show that the C-Mo-O coordination at the Mo2C/MoO2 interface can optimize the reaction path and reduce the energy barrier of the reaction intermediates, thereby enhancing the reaction kinetics of NRR.

Dual Starvations Induce Pyroptosis for Orthotopic Pancreatic Cancer Therapy through Simultaneous Deprivation of Glucose and Glutamine.

Pancreatic cancer is a highly fatal disease, and existing treatment methods are ineffective, so it is urgent to develop new effective treatment strategies. The high dependence of pancreatic cancer cells on glucose and glutamine suggests that disrupting this dependency could serve as an alternative strategy for pancreatic cancer therapy. We identified the vital genes glucose transporter 1 (GLUT1) and alanine-serine-cysteine transporter 2 (ASCT2) through bioinformatics analysis, which regulate glucose and glutamine metabolism in pancreatic cancer, respectively. Human serum albumin nanoparticles (HSA NPs) for delivery of GLUT1 and ASCT2 inhibitors, BAY-876/V-9302@HSA NPs, were prepared by a self-assembly process. This nanodrug inhibits glucose and glutamine uptake of pancreatic cancer cells through the released BAY-876 and V-9302, leading to nutrition deprivation and oxidative stress. The inhibition of glutamine leads to the inhibition of the synthesis of the glutathione, which further aggravates oxidative stress. Both of them lead to a significant increase in reactive oxygen species, activating caspase 1 and GSDMD and finally inducing pyroptosis. This study provides a new effective strategy for orthotopic pancreatic cancer treatment by dual starvation-induced pyroptosis. The study for screening metabolic targets using bioinformatics analysis followed by constructing nanodrugs loaded with inhibitors will inspire future targeted metabolic therapy for pancreatic cancer.

Photothermal modulation of gingival fibroblasts via polydopamine-coated zirconia: A novel approach for promoting peri-implant soft tissue integration.

Achieving robust soft tissue integration around dental implants is crucial for long-term clinical success, as it forms a protective biological seal against bacterial invasion. However, the soft tissue attachment to implants is relatively deficient compared to natural teeth, particularly in the connective tissue region lacking sufficient gingival fibroblasts and collagen fiber alignment. This study proposed an innovative strategy to enhance peri­implant soft tissue integration by modulating gingival fibroblast behavior via photothermal conversion. Zirconia surfaces were coated with polydopamine (PDA), a melanin-like polymer exhibiting near-infrared (NIR) absorption for photothermal conversion. Under NIR irradiation, the PDA coating enabled mild hyperthermia (42-43 °C) on the zirconia surface. Remarkably, this mild photothermal stimulation significantly promoted human gingival fibroblast proliferation, adhesion, and collagen production compared to unmodified zirconia in vitro. By utilizing the photothermal properties of PDA coatings to modulate cellular behaviors beneficial for connective tissue formation, this approach provides a promising avenue to achieve improved soft tissue integration and long-term stability of dental implants. The findings highlight the innovative potential of combining biomaterial surface engineering with photothermal therapy for applications in implant dentistry.

NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/ß-catenin pathway.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet the underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) is a widely expressed protein in OSCC, but its role in tumor development is unclear. This study aimed to explore NCAPD2 expression and its biological function in OSCC. NCAPD2 expression in OSCC cell lines and tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cancer cell growth was evaluated using cell proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and colony formation assays. Cell migration was evaluated using wound healing and Transwell assays. Apoptosis was detected using flow cytometry. The influence of NCAPD2 on tumor growth in vivo was evaluated in a mouse xenograft model. NCAPD2 expression was significantly higher in OSCC than that in normal oral tissue. In vitro, the knockdown of NCAPD2 inhibited OSCC cell proliferation and promoted apoptosis. NCAPD2 depletion also significantly inhibited the migration of OSCC cells. Moreover, NCAPD2 overexpression induced inverse effects on OSCC cell phenotypes. In vivo, we demonstrated that downregulating NCAPD2 could inhibit the tumorigenicity of OSCC cells. Mechanically, OSCC regulation by NCAPD2 involved the Wnt/ß-catenin signaling pathway. These results suggest NCAPD2 as a novel oncogene with an important role in OSCC development and a candidate therapeutic target for OSCC.

Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018.

AIMS: The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS: The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (ß = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (ß = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (ß = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05). CONCLUSION: These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.

Terpinen-4-ol from tea tree oil prevents Aspergillus flavus growth in postharvest wheat grain.

Plant volatile organic compounds (PVOCs) have gained increasing attention for their role in preventing fungal spoilage and insect contamination in postharvest agro-products owing to their effectiveness and sustainability. In this study, the essential oil was extracted from fresh M. alternifolia (tea tree) leaves, and the fumigation vapor of tea tree oil (TTO) completely inhibited the growth of Aspergillus flavus on agar plates at a concentration of 1.714 µL/mL. Terpinen-4-ol was identified as the major component (40.76 %) of TTO volatiles analyzed using headspace gas chromatography-mass spectrometry. Terpinen-4-ol vapor completely inhibited the A. flavus growth on agar plates and 20 % moisture wheat grain at 0.556 and 1.579 µL/mL, respectively, indicating that terpinen-4-ol serves as the main antifungal constituent in TTO volatiles. The minimum inhibitory concentration of terpinen-4-ol in liquid-contact culture was 1.6 µL/mL. Terpinen-4-ol treatment caused depressed, wrinkled, and punctured mycelial morphology and destroyed the plasma membrane integrity of A. flavus. Metabolomics analysis identified significant alterations in 93 metabolites, with 79 upregulated and 14 downregulated in A. flavus mycelia exposed to 1.6 µL/mL terpinen-4-ol for 6 h, involved in multiple cellular processes including cell membrane permeability and integrity, the ABC transport system, pentose phosphate pathway, and the tricarboxylic acid cycle. Biochemical analysis and 2,7-dichlorofluorescein diacetate staining showed that terpinen-4-ol induced oxidative stress and mitochondrial dysfunction in A. flavus mycelia. This study provides new insights into the antifungal effects of the main TTO volatile compounds terpinen-4-ol on the growth of A. flavus.

Rapid Initiation of Antiretroviral Therapy Under the Treat-All Policy Reduces Loss to Follow-Up and Virological Failure in Routine Human Immunodeficiency Virus Care Settings in China: A Retrospective Cohort Study (2016-2022).

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

Synergistic rosemary extract with TBHQ and citric acid improves oxidative stability and shelf life of peanut.

Lipid oxidation often accompanies the processing and storage of peanuts, which causes a serious waste of peanut resources. To solve the problem of being prone to oxidation in peanut processing, a ternary complex antioxidant based on rosemary extract (RE) was constructed to investigate its effect on the oxidative and thermal stability of peanuts, and the inhibition of peanut oxidation by compound antioxidants was revealed by dynamic Arrhenius formula and complexation theory. The results showed that there was a synergistic effect between RE and Tert-butyl hydroquinone (TBHQ), and the antioxidant effects of RE and TBHQ were 4.86 and 1.45 times higher when used in combination than when used alone, respectively. In addition, RE-TBHQ-CA (citric acid) effectively inhibited primary and secondary oxidation of peanuts with a shelf life 8.7 times longer than that of control peanuts. This study provides a novel antioxidant compounding idea, which has a positive effect on improving the quality of peanut and other nut products, prolonging the shelf life and reducing the waste of resources. PRACTICAL APPLICATION: Compounding a complex antioxidant that permits its use in peanuts. It was found that rosemary and TBHQ might have synergistic antioxidant effects. Meanwhile, this combination of RE-TBHQ-CA effectively inhibited the oxidation of peanut oils and prolonged the shelf life of peanuts. RE-TBHQ-CA is a highly efficient complex antioxidant that can reduce the amounts of antioxidants added while maintaining high antioxidant efficiency, which may be useful for the future preservation and storage of nut products as it positively affects the quality and shelf life of the product.

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition.

Hydroxytyrosol (HT), a phenolic extra-virgin olive oil compound used as a food supplement, has been recognized to protect liver function and alleviate stress-induced depressive-like behaviors. However, its protective effects against stress-induced liver injury (SLI) remain unknown. Here, the anti-SLI effect of HT was evaluated in mice with chronic unpredictable mild stress-induced SLI. Network pharmacology combined with molecular docking was used to clarify the underlying mechanism of action of HT against SLI, followed by experimental verification. The results showed that accompanying with the alleviation of HT on stress-induced depressive-like behaviors, HT was confirmed to exert the protective effects against SLI, as represented by reduced serum corticosterone (CORT), aspartate aminotransferase and alanine aminotransferase activities, as well as repair of liver structure, inhibition of oxidative homeostasis collapse, and inflammation reaction in the liver. Furthermore, core genes including histone deacetylase 1 and 2 (HDAC1/2), were identified as potential targets of HT in SLI based on bioinformatic screening and simulation. Consistently, HT significantly inhibited HDAC1/2 expression to maintain mitochondrial dysfunction in an autophagy-dependent manner, which was confirmed in a CORT-induced AML-12 cell injury and SLI mice models combined with small molecule inhibitors. We provide the first evidence that HT inhibits HDAC1/2 to induce autophagy in hepatocytes for maintaining mitochondrial dysfunction, thus preventing inflammation and oxidative stress for exerting an anti-SLI effect. This constitutes a novel therapeutic modality to synchronously prevent stress-induced depression-like behaviors and liver injury, supporting the advantaged therapeutic potential of HT.

Prenatal co-exposure to diisodecyl phthalate and ozone contribute to depressive behavior in offspring mice through oxidative stress and TWIST1 participation.

Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.