Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials.

Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

Prediction of lymph node metastasis in patients with papillary thyroid cancer based on radiomics analysis and intraoperative frozen section analysis: A retrospective study.

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Distribution, migration patterns, and food chain human health risks of endocrine-disrupting chemicals in water, sediments, and fish in the Xiangjiang River.

Exposure to endocrine-disrupting chemicals (EDCs) in freshwater systems has garnered increasing attention. A comprehensive analysis of the migration patterns, bioaccumulation, and consumer health risks of EDCs along the Xiangjiang River due to fish consumption from the river ecosystem was provided. Twenty natural and synthetic target EDCs were detected and analyzed from the water, sediments, and fish samples collected along the Xiangjiang River. There were significant correlations between the EDC concentrations in fish and the sediments. This revealed that EDCs in sediments play a dominant role in the uptake of EDCs by fish. The bioaccumulation factor and biota-sediment accumulation factor were calculated, with the highest values observed for nonylphenol. Pearson's correlation analysis showed that bisphenol A is the most reliable biological indicator of EDC contamination in fish. Furthermore, based on the threshold of toxicological concerns and the health risk with dietary intake, crucian carp and catfish from the Xiangjiang River pose a certain risk for children and pregnant women compared to grass carp. The Monte Carlo simulation results indicated a certain risk of cumulative ∑EDC exposure for local residents due to fish consumption.

Preventive effects of lactoferrin on acute alcohol-induced liver injury via iron chelation and regulation of iron metabolism.

Lactoferrin is widely found in milk and has the ability to bind iron. Previous studies have reported that lactoferrin was effective in the prevention and treatment of acute alcohol-induced liver injury (AALI). Ferroptosis is a recently discovered cell death and is involved in the development of AALI. However, the potential role of lactoferrin in acute alcohol-induced ferroptosis is still unclear. In this study, we observed that lactoferrin (10, 20 and 40 µg/mL) significantly mitigated alcohol (300 mM)-induced injury in vitro. Additionally, lactoferrin (100 and 200 mg/kg bw) significantly alleviated alcohol (4.8 g/kg bw)-induced injury in vivo. Our results showed that lactoferrin inhibited alcohol-induced upregulation of the ferroptosis marker protein ACSL4 and downregulation of GPX4. Meanwhile, lactoferrin treatment successfully reversed the elevated Malondialdehyde (MDA) levels and the reduced Glutathione (GSH) levels caused by alcohol treatment. These results can indicate that lactoferrin significantly decreased ferroptosis in vivo and in vitro. Lactoferrin has the potential to chelate iron, and our results showed that lactoferrin (20 µg/mL) significantly reduced iron ions and the expression of Ferritin Heavy Chain (FTH) under FeCl3 (100 µM) treatment. It was demonstrated that lactoferrin had a significant iron-chelating effect and reduced iron overload caused by FeCl3 in AML12 cells. Next, we examined iron content and the expression of iron metabolism marker proteins Transferrin Receptor (TFR), Divalent metal transporter 1 (DMT1), FTH, and Ferroportin (FPN). Our results showed that lactoferrin alleviated iron overload induced by acute alcohol. The expression of TFR and DMT1 was downregulated and FPN and FTH were upregulated after lactoferrin treatment in vivo and in vitro. Above all, the study suggested that lactoferrin can alleviate AALI by mitigating acute alcohol-induced ferroptosis. Lactoferrin may offer new strategies for the prevention or treatment of AALI.

Ubiquitinome Analysis Uncovers Alterations in Synaptic Proteins and Glucose Metabolism Enzymes in the Hippocampi of Adolescent Mice Following Cold Exposure.

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.

Comparison of initial percutaneous balloon compression versus radiofrequency thermocoagulation followed by percutaneous balloon compression in the treatment of trigeminal neuralgia. / 首次经皮球囊压迫术与射频热凝术后再行经皮球囊压迫术治疗三叉神经痛的比较.

OBJECTIVES: There are a variety of minimally invasive interventional treatments for trigeminal neuralgia, and the efficacy evaluation is different. The preferred treatment scheme is still controversial. This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia (PTN) treated with percutaneous balloon compression (PBC) for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation (RT) who then received PBC for PTN, and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. METHODS: We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021, including 49 patients who received PBC for the first time (PBC group) and 54 patients who received PBC for pain recurrence after RT (RT+PBC group). General information, preoperative pain score, intraoperative oval foramen morphology, oval foramen area, balloon volume, duration of compression, and postoperative pain scores and pain recurrence at each time point on day 1 (T1), day 7 (T2), day 14 (T3), 1 month (T4), 3 months (T5), and 1 year (T6) were collected and recorded for both groups. The differences in treatment effect, complications and recurrence between the 2 groups were compared, and the related influencing factors were analyzed. RESULTS: The differences of general information, preoperative pain scores, foramen ovale morphology, foramen ovale area, T1 to T3 pain scores between the 2 groups were not statistically different (all P>0.05). The balloon filling volume in the PBC group was smaller than that in the RT+PBC group, the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group (all P<0.05). Pain recurrence was positively correlated with pain scores of T2 to T6 (r=0.306, 0.482, 0.831, 0.876, 0.887, respectively; all P<0.01). CONCLUSIONS: The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Technique for enhancing the accuracy of the Rayleigh-Sommerfeld convolutional diffraction through the utilization of independent spatial sampling: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 1385 (2024)10.1364/OL.509688.

PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer.

Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer.

Genome-wide identification, subcellular localization, and expression analysis of the phosphatidyl ethanolamine-binding protein family reveals the candidates involved in flowering and yield regulation of Tartary buckwheat (Fagopyrum tataricum).

Background: PEBP (phosphatidyl ethanolamine-binding protein) is widely found in eukaryotes including plants, animals and microorganisms. In plants, the PEBP family plays vital roles in regulating flowering time and morphogenesis and is highly associated to agronomic traits and yields of crops, which has been identified and characterized in many plant species but not well studied in Tartary buckwheat (Fagopyrum tataricum Gaertn.), an important coarse food grain with medicinal value. Methods: Genome-wide analysis of FtPEBP gene family members in Tartary buckwheat was performed using bioinformatic tools. Subcellular localization analysis was performed by confocal microscopy. The expression levels of these genes in leaf and inflorescence samples were analyzed using qRT-PCR. Results: Fourteen Fagopyrum tataricum PEBP (FtPEBP) genes were identified and divided into three sub-clades according to their phylogenetic relationships. Subcellular localization analysis of the FtPEBP proteins in tobacco leaves indicated that FT- and TFL-GFP fusion proteins were localized in both the nucleus and cytoplasm. Gene structure analysis showed that most FtPEBP genes contain four exons and three introns. FtPEBP genes are unevenly distributed in Tartary buckwheat chromosomes. Three tandem repeats were found among FtFT5/FtFT6, FtMFT1/FtMFT2 and FtTFL4/FtTFL5. Five orthologous gene pairs were detected between F. tataricum and F. esculentum. Seven light-responsive, nine hormone-related and four stress-responsive elements were detected in FtPEBPs promoters. We used real-time PCR to investigate the expression levels of FtPEBPs among two flowering-type cultivars at floral transition time. We found FtFT1/FtFT3 were highly expressed in leaf and young inflorescence of early-flowering type, whereas they were expressed at very low levels in late-flowering type cultivars. Thus, we deduced that FtFT1/FtFT3 may be positive regulators for flowering and yield of Tartary buckwheat. These results lay an important foundation for further studies on the functions of FtPEBP genes which may be utilized for yield improvement.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Inhalable FN-binding liposomes or liposome-exosome hybrid bionic vesicles encapsulated microparticles for enhanced pulmonary fibrosis therapy.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease that seriously threatens human life and health. Our previous study demonstrated the unique superiority of traditional Chinese medicine cryptotanshinone (CTS) combined with sustained pulmonary drug delivery for treating PF. In this study, we aimed to enhance the selectivity, targeting efficiency and sustained-release capability based on this delivery system. To this end, we developed and evaluated CTS-loaded modified liposomes-chitosan (CS) microspheres SM(CT-lipo) and liposome-exosome hybrid bionic vesicles-CS microspheres SM(LE). The prepared nano-in-micro particles system integrates the advantages of the carriers and complements each other. SM(CT-lipo) and SM(LE) achieved lung myofibroblast-specific targeting through CREKA peptide binding specifically to fibronectin (FN) and the homing effect of exosomes on parent cells, respectively, facilitating efficient delivery of anti-fibrosis drugs to lung lesions. Furthermore, compared with daily administration of conventional microspheres SM(NC) and positive control drug pirfenidone (PFD), inhaled administration of SM(CT-lipo) and SM(LE) every two days still attained similar efficacy, exhibiting excellent sustained drug release ability. In summary, our findings suggest that the developed SM(CT-lipo) and SM(LE) delivery strategies could achieve more accurate, efficient and safe therapy, providing novel insights into the treatment of chronic PF.

Redundancy effect of initial enactment encoding and subsequent testing on memory enhancement: Insights from an electrophysiological study.

Testing is more beneficial for memory retention than restudying the same content. However, the effect of the initial encoding method on the testing effect remains unclear. In this study, a classical testing effect paradigm was employed, along with event-related potentials (ERP), to investigate the electrophysiological processes underlying the effect of enactment encoding on the testing effect. Participants were randomly assigned to the Self-Performed Test (SPT) or Verbalized Test (VT) groups. Both groups underwent three stages: an initial encoding phase, an initial test phase (comprising a source memory task and a restudy task), and a final test phase. During the initial encoding phase, the SPT group encoded action phrases through enactment, while the VT group encoded information through reading. During the initial test phase, the SPT group exhibited superior recognition performance in item memory compared with the VT group. Both groups exhibited significant parietal old/new effects in the source memory task, with only the SPT group displaying parietal positivity during the restudy task. During the final test phase, the behavioral testing effect was exclusively observed in the VT group. Furthermore, the VT group displayed a more pronounced parietal positivity in the test condition compared to the restudy condition, while the parietal positivity between the two conditions was comparable in the SPT group. In summary, the absence of a final behavioral testing effect in the SPT group may be attributed to both enactment and testing primarily enhancing memory performance through recollection-based retrieval, as indicated by the parietal positivity. Consequently, the initial enactment encoding method leaves limited scope for further improvements through subsequent testing. These findings suggest that initial enactment encoding, and subsequent testing may be redundant in improving episodic memory performance.

Reduced-dose chemotherapy followed by blinatumomab in induction therapy for newly diagnosed B-cell acute lymphoblastic leukemia.

BACKGROUND: Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes. METHODS: We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy. RESULTS: At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10-4 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported. CONCLUSIONS: Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.

Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences. ASD is more commonly diagnosed in males at a ratio of 4:1, indicating a potential oversight in female-specific ASD research and a risk of underdiagnosis in females. We consider how ASD manifests differently across sexes by exploring differential gene expression in female and male brains and consider how variations in steroid hormones influence ASD characteristics. Synaptic function, including excitation/inhibition ratio imbalance, is influenced by gene mutations and this is explored as a key factor in the cognitive and behavioural manifestations of ASD. We also discuss the role of micro RNAs (miRNAs) and highlight a novel mutation in miRNA-873, which affects a suite of key synaptic genes, neurexin, neuroligin, SHANK and post-synaptic density proteins, implicated in the pathology of ASD. Our review suggests that genetic predisposition, sex differences in brain gene expression, and hormonal factors significantly contribute to the presentation, identification and severity of ASD, necessitating sex-specific considerations in diagnosis and treatments. These findings advocate for personalized interventions to improve the outcomes for individuals with ASD.

Intestinal microbiota modulates neuroinflammatory response and brain injury after neonatal hypoxia-ischemia.

Premature infants lack a normal intestinal microbial community and also at risk of perinatal hypoxic-ischemic (HI) brain injury, which is considered to be one of the major factors for motor, sensory, and cognitive deficits. We hypothesized that neonatal gut microbiota composition modulated the immune reaction and severity of neonatal H-I brain injury. Neonatal C57BL/6J mouse pups were exposed to H-I protocol consisting of permanent left carotid artery ligation, followed by 8% hypoxia for 60 min. Microbial manipulation groups included 1) antibiotic treatment, E18 (maternal) to P5; 2) antibiotic treatment E18 to P5 + E. coli gavage; 3) antibiotic treatment E18 to P5 + B. infantis gavage; and 4) saline to pups with dams getting fresh water. The extent of brain injury and recovery was measured on MRI. Edematous injury volume was significantly higher in E. coli group than that in B. infantis group and in fresh water group. Gene expression in brains of pro-inflammatory cytokines (IL1ß, IL6, IL2, TNF-α and toll-like receptors 2-6) were elevated to a greater extent in the E. coli group at P10, no injury, and at P13, 72 hours after H-I relative to sham control and B. infantis groups. Significant effects of microbiome and brain injury and interaction of these factors were found in abundance of major phyla. The neuroinflammatory response and brain injury after neonatal hypoxia-ischemia are affected by intestinal microbiota, providing opportunities for therapeutic intervention through targeting the early colonization and development of the gut microbiota.

Phage resistance in Klebsiella pneumoniae and bidirectional effects impacting antibiotic susceptibility.

OBJECTIVES: Bacteriophage (phage) therapy is a promising anti-infective option to combat antimicrobial resistance. However, the clinical utilization of phage therapy has been severely compromised by the potential emergence of phage resistance. Although certain phage resistance mechanisms can restore bacterial susceptibility to certain antibiotics, a lack of knowledge of phage resistance mechanisms hinders optimal use of phages and their combination with antibiotics. METHODS: Genome-wide transposon screening was performed with a mutant library of Klebsiella pneumoniae MKP103 to identify phage pKMKP103_1-resistant mutants. Phage-resistant phenotypes were evaluated by time-kill kinetics and efficiency of plating assays. Phage resistance mechanisms were investigated with adsorption, one-step growth, and mutation frequency assays. Antibiotic susceptibility was determined with broth microdilution and population analysis profiles. RESULTS: We observed a repertoire of phage resistance mechanisms in K pneumoniae, such as disruption of phage binding (fhuA::Tn and tonB::Tn), extension of the phage latent period (mnmE::Tn and rpoN::Tn), and increased mutation frequency (mutS::Tn and mutL::Tn). Notably, in contrast to the prevailing view that phage resistance re-sensitizes antibiotic-resistant bacteria, we observed a bidirectional steering effect on bacterial antibiotic susceptibility. Specifically, rpoN::Tn increased susceptibility to colistin while mutS::Tn and mutL::Tn increased resistance to rifampicin and colistin. DISCUSSION: Our findings demonstrate that K pneumoniae employs multiple strategies to overcome phage infection, which may result in enhanced or reduced antibiotic susceptibility. Mechanism-guided phage steering should be incorporated into phage therapy to better inform clinical decisions on phage-antibiotic combinations.

Enhancing the stability of mung bean-based milk: Insights from protein characteristics and raw material selection.

Plant-based milk (PBM) alternatives are gaining popularity worldwide as the change of consumers' nutritional habits and health attitudes. Mung beans, recognized for their nutritional value, have gained attention as potential ingredients for PBM. Nevertheless, mung bean-based milk (MBM) faces instability issues common to other plant-based milks. This study investigated the factors influencing MBM stability focusing on raw materials. We selected 6 out of 20 varieties based on their MBM centrifugation sedimentation rates, representing both stable and unstable MBM. Stable MBM exhibited distinct advantages, including reduced separation rate, smaller particle size, lower viscosity, fewer protein aggregates, higher soluble protein content, and increased consumer acceptance. Major nutritional components such as protein, starch, and lipids were not significant different between stable and unstable MBM varieties. The pivotal distinction may lay in the protein properties and composition. Stable MBM varieties exhibited significantly improved protein solubility and emulsion stability, along with elevated concentrations of legume-like acidic subunits, basic 7S proteins, and 28 kDa and 26 kDa vicilin-like subunits. The increasement of these proteins likely contributed to the improvement in protein characteristics that affect MBM stability. These findings offer valuable insights for raw material selection and guidance for future mung bean breeding to enhance mung bean milk production.

Structural characterization of a novel polysaccharide from Tremella fuciformis and its interaction with gut microbiota.

BACKGROUND: Because of their diverse biological activities, polysaccharides derived from Tremella fuciformis have received growing attention. This study aimed to investigate the structural characterization of a purified polysaccharide (designated as PTP-3a) derived from T. fuciformis and explore its interaction with gut microbiota in vitro. RESULTS: The findings revealed that PTP-3a had a molecular weight of 1.22 × 103 kDa and consisted of fucose, glucose, xylose, mannose and glucuronic acid in a molar ratio of 0.271:0.016:0.275:0.400:0.038. The primary linkage types identified in PTP-3a were 1,3-linked-manp, 1,4-linked-xylp and 1,2,3-linked-fucp, with corresponding ratios of 0.215:0.161:0.15. In addition, PTP-3a demonstrated notable thermal stability and exhibited a triple-helical structure. Moreover, following in vitro fermentation for 48 h, PTP-3a was efficiently utilized, resulting in a reduction in carbohydrate levels, the production of short-chain fatty acids (SCFAs) and pH adjustment. Furthermore, during in vitro fecal microbial fermentation, PTP-3a decreased the relative abundance of Firmicutes while increasing the proportions of Bacteroidetes and Proteobacteria, resulting in a significantly reduced Firmicutes/Bacteroidetes ratio. Additionally, PTP-3a stimulated the growth of beneficial bacteria such as Parabacteroides merdae, Gordonibacter pamelaeae, Bifidobacterium pseudolongum and Parabacteroides distasonis. Importantly, a strong correlation was observed between the production of SCFAs and specific microorganisms. CONCLUSION: These findings suggested that PTP-3a has potential as a prebiotic for modulating the gut microbiota. © 2024 Society of Chemical Industry.