Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease.

The aggregation and prion-like propagation of α-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of α-synuclein fibrils remain poorly understood. Tau co-deposits with α-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with α-synuclein and accelerates its aggregation. Compared with pure α-synuclein fibrils, the tau-modified α-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified α-synuclein fibrils into the striatum of mice induces more severe α-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure α-synuclein fibrils. Knockout of tau attenuates the propagation of α-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with α-syn fibrils and α-syn A53T transgenic mice. In conclusion, tau facilitates α-synuclein aggregation and propagation in Parkinson's disease.

Comparative analysis of whey proteins in yak milk from different breeds in China using a data-independent acquisition proteomics method.

Yak milk is rich in essential milk proteins of nutritional and therapeutic value. In this study, whey proteins of milk from 3 yak breeds (Gannan, GN; Huanhu, HH; Maiwa, MW) in China were comprehensively identified and compared using a data-independent acquisition quantitative proteomics approach. A total of 632 proteins were identified in yak milk whey samples, in which immune-related proteins were abundant. Compared with other milks, more proteins were involved in oxidation-reduction process and with ATP binding. In addition, we identified 96, 155, and 164 differentially expressed proteins (DEP) for GN versus HH, GN versus MW, and HH versus MW, respectively. "Phagosome" and "complement and coagulation cascades" were the most significant pathways for DEP of GN versus HH and GN or HH versus MW yak milk based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein-protein interaction network analysis showed that DEP for the 3 comparisons had significant biological interactions but were associated with different functions. The results provide useful information on yak milk from different breeds in China, and elucidate the biological functions of yak milk proteins.

Enhancing lactose recognition of a key enzyme in 2'-fucosyllactose synthesis: α-1,2-fucosyltransferase.

BACKGROUND: 2'-Fucosyllactose, a representative oligosaccharide in human milk, is an emerging and promising food and pharmaceutical ingredient due to its powerful health benefits, such as participating in immune regulation, regulation of intestinal flora, etc. To enable economically viable production of 2'-fucosyllactose, different biosynthesis strategies using precursors and pathway enzymes have been developed. The α-1,2-fucosyltransferases are an essential part involved in these strategies, but their strict substrate selectivity and unsatisfactory substrate tolerance are one of the key roadblocks limiting biosynthesis. RESULTS: To tackle this issue, a semi-rational manipulation combining computer-aided designing and screening with biochemical experiments were adopted. The mutant had a 100-fold increase in catalytic efficiency compared to the wild-type. The highest 2'-fucosyllactose yield was up to 0.65 mol mol-1 lactose with a productivity of 2.56 g mL-1  h-1 performed by enzymatic catalysis in vitro. Further analysis revealed that the interactions between the mutant and substrates were reduced. The crucial contributions of wild-type and mutant to substrate recognition ability were closely related to their distinct phylotypes in terms of amino acid preference. CONCLUSION: It is envisioned that the engineered α-1,2-fucosyltransferase could be harnessed to relieve constraints imposed on the bioproduction of 2'-fucosyllactose and lay a theoretical foundation for elucidating the substrate recognition mechanisms of fucosyltransferases. © 2022 Society of Chemical Industry.

7,8-Dihydroxyflavone ameliorates mitochondrial impairment and motor dysfunction in the α-synuclein 1-103 transgenic mice.

Parkinson's disease (PD) is the most common motor-associated neurodegenerative disease. Although the pathogenesis of PD is still wrapped in the mist, accumulating evidence indicates that mitochondrial dysfunction contributes to the onset and progression of PD. We previously reported that the lysosomal protease asparagine endopeptidase (AEP) cleaves α-synuclein in the brains of PD patients. The major product, α-synuclein 1-103, significantly promotes PD-like histological changes and motor dysfunction. However, the underlying molecular mechanisms remain unknown. Here we show that α-synuclein 1-103 fragment interacts with mitochondria and induces morphological and functional abnormalities of mitochondria. Furthermore, we investigated the protective effects of 7,8-dihydroxyflavone (7,8-DHF) on mitochondrial dysfunction induced by α-synuclein 1-103 fragment. We found that 7,8-DHF ameliorated α-synuclein 1-103-induced mitochondrial impairment and motor dysfunction. These results indicate that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating PD.

Fine Particulate Matter Triggers α-Synuclein Fibrillization and Parkinson-like Neurodegeneration.

BACKGROUND: The deposition of α-synuclein (α-Syn) in the brain is the pathological hallmark of Parkinson's disease (PD). Epidemiological data indicate that exposure to fine particulate matter (≤2.5 µm in aerodynamic diameter [PM2.5]) is associated with an increased risk for PD. OBJECTIVE: The aim of this study is to investigate whether PM2.5 has a direct effect on α-Syn pathology and how it drives the risk for PD. METHODS: PM2.5 was added into α-Syn monomers and different cell models to test whether PM2.5 can promote the fibrillization and aggregation of α-Syn. α-Syn A53T transgenic mice and α-Syn knockout mice were used to investigate the effects of PM2.5 on PD-like pathology. RESULTS: PM2.5 triggers the fibrillization of α-Syn and promotes the formation of α-Syn fibrils with enhanced seeding activity and neurotoxicity. PM2.5 also induces mitochondrial dysfunction and oxidative stress. Intrastriatal injection or intranasal administration of PM2.5 exacerbates α-Syn pathology and dopaminergic neuronal degeneration in α-Syn A53T transgenic mice. The detrimental effect of PM2.5 was attenuated in α-Syn knockout mice. CONCLUSIONS: Our results identify that PM2.5 exposure could promote the α-Syn pathology, providing mechanistic insights into how PM2.5 increases the risk for PD. © 2022 International Parkinson and Movement Disorder Society.

Enhancing heterologous expression of a key enzyme for the biosynthesis of 2'-fucosyllactose.

BACKGROUND: 2'-Fucosyllactose (2'-FL) is the most abundant human milk oligosaccharide (HMO) in human milk and has important physiological functions. The market demand of 2'-FL is continuing to grow, but high production cost has limited its availability. To solve the dilemma, biosynthesis of 2'-FL has been proposed and is considered the most promising pathway for massive production. α-1,2-Fucosyltransferase is one of the key elements involved in its biosynthesis, but the limited intracellular accumulation and unstable properties of α-1,2-fucosyltransferases when expressed in host strains have become a major hurdle for the effective biosynthesis of 2'-FL. RESULTS: A combinatorial engineering strategy of synergic modification of ribosome binding site, fusion peptide and enzyme gene was leveraged to enhance the soluble expression of α-1,2-fucosyltransferases and promote enzyme activity. The preferable combination was to employ an optimized ribosome binding site region to drive 3 × FLAG as a fusion partner along with the α-1,2-fucosyltransferase for expression in Escherichia coli (DE3) PlySs, and protein yield and enzyme activity were remarkably improved by 11.51-fold and 13.72-fold, respectively. CONCLUSION: After finely tuning the synergy among different elements, the abundant protein yield and high enzyme activity confirmed that the drawbacks of heterologous expression in α-1,2-fucosyltransferase had been properly addressed. A suitable external environment further drives the efficient synthesis of α-1,2-fucosyltransferases. To our knowledge, this is the first report of a systematic and effective modification of α-1,2-fucosyltransferase expression, which could potentially serve as a guideline for industrial application. © 2022 Society of Chemical Industry.

Asparagine endopeptidase cleaves synaptojanin 1 and triggers synaptic dysfunction in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway. Synaptic dysfunction impairs dopamine turnover and contributes to the degeneration of dopaminergic neurons. However, the molecular mechanisms underlying synaptic dysfunction and dopaminergic neuronal vulnerability in PD are not clear. Here, we report that synaptojanin 1 (SYNJ1), a polyphosphoinositide phosphatase concentrated at nerve terminals, is a substrate of a cysteine proteinase, asparagine endopeptidase (AEP). SYNJ1 is cleaved by the cysteine proteinase AEP at N599 in the brains of PD patients. AEP-mediated cleavage of SYNJ1 disrupts neuronal phosphoinositide homeostasis and causes synaptic dysfunction. Overexpression of the AEP-generated fragments of SYNJ1 triggers synaptic dysfunction and the degeneration of dopaminergic neurons, inducing motor defects in the α-synuclein transgenic mice. Blockage of AEP-mediated cleavage of SYJN1 alleviates the pathological and behavioral defects in a mouse model of PD. Our results demonstrate that the fragmentation of SYNJ1 by AEP mediates synaptic dysfunction and dopaminergic neuronal degeneration in PD.

KRAS G12V mutation upregulates PD-L1 expression via TGF-ß/EMT signaling pathway in human non-small-cell lung cancer.

Although clinical data suggest remarkable promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small-cell lung cancer (NSCLC), it is still largely undetermined which subtype of patients will be responsive to checkpoint blockade. In the present study, we explored whether PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog (KRAS), which is frequently mutated in NSCLC and results in poor prognosis and low survival rates. We verified that PD-L1 levels were dramatically increased in KRAS mutant cell lines, particularly in NCI-H441 cells with KRAS G12V mutation. Overexpression of KRAS G12V remarkably elevated PD-L1 messenger RNA and protein levels, while suppression of KRAS G12V led to decreased PD-L1 levels in NCI-H441 cells. Consistently, higher levels of PD-L1 were observed in KRAS-mutated tissues as well as tumor tissues-derived CD4+ and CD8+ T cells using a tumor xenograft in B-NDG mice. Mechanically, both in vitro and in vivo assays found that KRAS G12V upregulated PD-L1 via regulating the progression of epithelial-to-mesenchymal transition (EMT). Moreover, pembrolizumab activated the antitumor activity and decreased tumor growth with KRAS G12V mutated NSCLC. This study demonstrates that KRAS G12V mutation could induce PD-L1 expression and promote immune escape via transforming growth factor-ß/EMT signaling pathway in KRAS-mutant NSCLC, providing a potential therapeutic approach for NSCLC harboring KRAS mutations.

Dietary patterns of Chinese puerperal women and their association with postpartum weight retention: Results from the mother-infant cohort study.

Dietary intake may affect maternal health, but it remains unclear about puerperal dietary intake and its association with maternal health. This study investigated the dietary patterns and their related factors and association with postpartum weight retention (PPWR) in Chinese puerperal women. Participants were from the mother-infant cohort study, in which both mothers and infants were followed up from childbirth to the next 2 years, in seven cities around China. Maternal puerperal dietary patterns were derived by a food frequency questionnaire and principal component analysis (PCA) within 1 month postpartum. PPWR was assessed by the difference of weight at 42 days and 6 months postpartum minus the pre-pregnancy weight. Of 503 postpartum women, four dietary patterns were identified, including 'plant food' pattern (rice and vegetables as dominant foods), 'diverse' pattern (starchy roots, fruit, livestock meat and aquatic products), 'traditional northern' pattern (poultry, eggs and soup) and 'marine-flour' pattern (flour, coarse food grains and marine fish). The diverse pattern was associated with professional puerperal family care and counselling service (p < .05). PPWRs at 42 days and 6 months postpartum were 6.37 and 4.70 kg averagely. The plant food dietary pattern tended to be associated with higher 42-day PPWR (ß = .105, p < .05), and diverse pattern was associated with lower 6-months PPWR (ß = -.137, p < .05). Conclusively, this study presented four dominant dietary patterns in Chinese postpartum women and showed a lower PPWR in adherence to diverse dietary pattern. The results would provide evidence to furtherly guide dietary practice and improve maternal health.

Maternal postpartum feeding anxiety was associated with infant feeding practices: results from the mother-infant cohort study of China.

BACKGROUND: Maternal feeding anxiety (FA) was prevalent during puerperium and might affect infant feeding practices. This study was aimed to investigate the FA status in Chinese postpartum women and its relationship with infant feeding practices (FPs). METHODS: Participants were from the Mother-Infant Cohort Study of China, in which the dietary and feeding practices, physical and psychiatric health for both mothers and infants were followed up from childbirth to next 2 years. In this study the maternal feeding anxiety (FA) status at 0-3 months postpartum was assessed by Li's Self-rating Feeding Anxiety Scale (SFAS). Infant feeding practices (FPs) at 0-3 months, including breastfeeding-related behaviors, responsive feeding and infant food refusal were investigated by self-designed questionnaire. RESULTS: In total 456 mothers the average feeding anxiety scores (FAS) was 41.02 ± 8.02 (mean ± SD), and maternal FA prevalence were 61.4% (FAS>38) with severe FA being 8.6% (FAS>52) at 0-3 months postpartum. The FAS was related with infant FPs, and lower maternal FAS was significantly related with infant colostrum feeding (40.86 ± 8.02 vs 44.74 ± 11.33, P < 0.05), but higher FAS was related with bottle feeding (41.95 ± 8.28 vs 39.69 ± 7.92, P < 0.05). The mothers with severe feeding anxiety (FAS > 53) were more likely to feed infants with bottle (ORs, 95%CI: 2.41, 1.11 ~ 5.19). There were not significant association between FAS and exclusive breastfeeding and responsive feeding practices (P > 0.05). The higher FAS was associated with infant food refusal behaviors, the maternal scores whose infant "never", "rarely", "sometimes" and "often" spat out food when feeding were 39.86 ± 8.02, 41.47 ± 8.18, 41.36 ± 7.44 and 42.14 ± 12.03 increasingly (P > 0.05), and the FA prevalence was significantly different among groups (P < 0.05). The infants whose mother was identified as feeding anxiety were more likely to refuse opening the mouth when feeding (P < 0.05). Multivariate analysis indicated maternal FAS was positively related to infant bottle feeding (ßi = 2.487, P < 0.05) and outdoor sunshine exposure practice (ßi = 1.787, P < 0.05), and negatively related to household income level (ßi = - 0.118, P < 0.05). CONCLUSIONS: Maternal postpartum feeding anxiety was associated with some infant feeding practices, including bottle feeding and infant food refusal behaviors.

Isolation and characterization of lactic acid bacteria from human milk.

Human milk is the main source of nutrition for infants and the transmission of various microorganisms. The lactic acid bacteria (LAB) in breast milk allow for the establishment of the gut microflora of infants. In this study, we aimed to assess the probiotic potential of LAB strains isolated from breast milk of healthy Chinese women. Two strains, Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus) LHL6 and LHL7, were selected and identified through morphology observation, Gram staining, and 16S rDNA phylogenetic analysis. Using Limosilactobacillus fermentum (formerly Lactobacillus fermentum) CECT5716 as the standard reference strain, the screened strains were characterized for aspects of growth, production of lactic acid and H2O2, antibiotic susceptibility, survival under simulated gastrointestinal conditions, and tolerance to cadmium (Cd). In de Man, Rogosa, and Sharpe (MRS) broth, LHL6 and LHL7 showed longer lag phases than CECT5716 but higher specific growth rates. For the production of lactic acid and H2O2, LHL7 performed better than LHL6 and CECT5716, indicating better antimicrobial ability. Strain LHL7 generated 9.99 mg/L H2O2, considerably higher than 1.25 mg/L for LHL6 and 2.33 mg/L for CECT5716. According to European Food Safety Authority minimum inhibitory concentrations, all of the investigated strains were resistant to chloramphenicol, streptomycin, and kanamycin. However, unlike LHL6 and CECT5716, LHL7 was susceptible to ampicillin and resistant to tetracycline. Resistance to azithromycin, cephalexin, and penicillin G were similar for all 3 strains, whereas CECT5716 was resistant to a higher concentration of roxithromycin. All 3 strains were able to survive in a simulated gastric-like solution, but a low percentage survived in the presence of 0.4% bile salt and 7% pancreatin. Encapsulation with protectants may enhance the survival rate. All 3 strains were tolerant to 500 mg/L Cd in MRS broth and to 1,000 mg/L Cd on MRS agar medium. In summary, 2 novel strains of LAB were obtained that have similar characteristics to the reference strain CECT5716. This work identified potential probiotic candidates for application in the food and pharmaceutical industries and facilitated identification of further probiotics.

Activation of the STAT3/microRNA-21 pathway participates in angiotensin II-induced angiogenesis.

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII-induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA-21 (miR-21) in the AngII-mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR-21 was found to be upregulated in AngII-treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII-mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR-21 expression, which was verified by ChIP-PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR-21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR-21, and STAT3 inhibition restored AngII-induced reduction in PTEN. Similarly, the STAT3/miR-21 axis was shown to mediate AngII-provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR-21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII-induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.

MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF.

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3'-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3'-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K-AKT and epilthelial-mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers.

miR-100 promotes the proliferation of spermatogonial stem cells via regulating Stat3.

Micro RNAs play important roles during mammalian spermatogenesis, but the function(s) of specific miRNAs remain largely unknown. Here, we report that miR-100 is predominantly expressed in undifferentiated murine spermatogonia, including spermatogonial stem cells (SSCs). We utilized a miRNA mimic and inhibitor to knock down and overexpress miR-100 in cultured SSCs, respectively, finding that the miR-100 promotes the proliferation of SSCs in vitro. Furthermore, signals promoting SSC maintenance induced, whereas retinoic acid repressed, expression of miR-100. Stat3 expression was modulated by miR-100, with increased transcript and protein abundance in the presence of the miR-100 inhibitor versus reduced protein levels following miR-100 overexpression. Stat3 silencing also mimicked the reduced SSC proliferation phenotype associated with elevated miR-100 levels. Importantly, Stat3 silencing rescued the anti-proliferation capacity of miR-100 inhibitor on cultured SSCs. Given that the Stat3 3' untranslated region was not repressed by pre-miR-100 in a standard luciferase reporter assay, we suggest that miR-100 promotes SSC proliferation by indirect regulation of Stat3.

Identification of the E3 deubiquitinase ubiquitin-specific peptidase 21 (USP21) as a positive regulator of the transcription factor GATA3.

The expression of the transcription factor GATA3 in FOXP3(+) regulatory T (Treg) cells is crucial for their physiological function in limiting inflammatory responses. Although other studies have shown how T cell receptor (TcR) signals induce the up-regulation of GATA3 expression in Treg cells, the underlying mechanism that maintains GATA3 expression in Treg cells remains unclear. Here, we show how USP21 interacts with and stabilizes GATA3 by mediating its deubiquitination. In a T cell line model, we found that TcR stimulation promoted USP21 expression, which was further up-regulated in the presence of FOXP3. The USP21 mutant C221A reduced its capacity to stabilize GATA3 expression, and its knockdown led to the down-regulation of GATA3 protein expression in Treg cells. Furthermore, we found that FOXP3 could directly bind to the USP21 gene promoter and activated its transcription upon TcR stimulation. Finally, USP21, GATA3, and FOXP3 were found up-regulated in Treg cells that were isolated from asthmatic subjects. In summary, we have identified a USP21-mediated pathway that promotes GATA3 stabilization and expression at the post-translational level. We propose that this pathway forms an important signaling loop that stabilizes the expression of GATA3 in Treg cells.

Deubiquitination and stabilization of T-bet by USP10.

The T-box transcriptional factor T-bet is crucial in the development, differentiation and function of Th1 cells. It drives Th1 immune response primarily through promoting expression of Th1 hallmark cytokine IFN-γ. Although T-bet was found associated with many immune-mediated diseases such as asthma and systemic sclerosis, little is known about the regulation of T-bet stability and function. Here we identified USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus. Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet. We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10. Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way. Moreover, we found USP10 expression was upregulated in asthmatic patient PBMC, suggesting USP10 may maintain high level of T-bet and IFN-γ to fight against Th2-dominated inflammation.

Conversion of yellow wine lees into high-protein yeast culture by solid-state fermentation.

This study is focussed on the possibility of producing a yeast culture with yellow wine lees as a substrate by solid-state fermentation (SSF). Results showed that a yeast count of 1.58 × 109 CFU/g was achieved by signal factor and orthogonal experiments. After fermentation, the starch content in the yeast culture reduced from 32.2% ± 0.5% to 7.5% ± 0.2%, and the contents of crude protein and peptide increased from 36.1% ± 0.8% to 48.0% ± 1.0% and 3.9% ± 0.2% to 7.2% ± 0.4%, respectively. Additionally, large amounts of short peptides and free amino acids were detected by fast protein liquid chromatography (FPLC). These results suggest that yellow wine lees are a suitable substrate for the production of yeast cultures. It can serve as a growth-promoting factor and help reduce the shortage of protein feed in the animal industry. This research provides a potential way for the utilization of agro-industrial residues.

Retraction of: "Risk factors for poor ovarian response in patients receiving in-vitro fertilization and embryo transfer".

The paper entitled "Risk factors for poor ovarian response in patients receiving in-vitro fertilization and embryo transfer" by Chen et al., which was published in Minerva Surgery 2023 June;78(3):303-4, has been retracted by the Publisher upon the authors' request; they asked for a retraction because the paper contains faulty data.

Effect of NH4+ and NO3- cooperatively regulated carbon to nitrogen ratio on organic nitrogen fractions during rice straw composting.

The purpose of this study was to examine the effects of replacing urea with inorganic nitrogen on the organic nitrogen sequestration process and the mitigation of nitrogen loss during rice straw composting. These groups include a control group with urea addition (CK), a group with (NH4)2SO4 addition (NH), a group with KNO3 addition (NO), and a group with (NH4)2SO4 + KNO3 addition (NN). The results demonstrated that adding NH, NO, and NN significantly increased the content of bioavailable organic nitrogen in the composting. Furthermore, compared to the CK, the NH treatment reduced nitrogen loss by 8.41 %. Structural equation modeling revealed the correlation between bacterial communities and organic nitrogen fractions in different treatment groups. Comparisons of nitrogen efficacy and nitrogen loss indicated that adding (NH4)2SO4 was more effective during composting, which provided a meaningful research basis for rice straw composting.