Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Ginkgolide C attenuated Western diet-induced non-alcoholic fatty liver disease via increasing AMPK activation.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a metabolic dysregulation-related disorder that is generally characterized by lipid metabolism dysfunction and an excessive inflammatory response. Currently, there are no authorized pharmacological interventions specifically designed to manage NASH. It has been reported that Ginkgolide C exhibits anti-inflammatory effects and modulates lipid metabolism. However, the impact and function of Ginkgolide C in diet-induced NASH are unclear. METHODS: In this study, mice were induced by a Western Diet (WD) with different doses of Ginkgolide C with or without Compound C (adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor). The effects of Ginkgolide C were evaluated by assessing liver damage, steatosis, fibrosis, and AMPK expression. RESULTS: The results showed that Ginkgolide C significantly alleviated liver damage, steatosis, and fibrosis in the WD-induced mice. In addition, Ginkgolide C markedly improved insulin resistance and attenuated hepatic inflammation. Importantly, Ginkgolide C exerted protective effects by activating the AMPK signaling pathway, which was reversed by AMPK inhibition. CONCLUSION: Ginkgolide C alleviated NASH induced by WD in mice, potentially via activating the AMPK signaling pathway.

Probiotic Lactobacillus rhamnosus GG improves insulin sensitivity and offspring survival via modulation of gut microbiota and serum metabolite in a sow model.

BACKGROUND: Sows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG (n = 10) and control group (n = 10). RESULTS: In sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota. CONCLUSIONS: We provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

The role of cytolethal distending toxin in Glaesserella parasuis JS0135 strain infection: Cytotoxicity, phagocytic resistance and pathogenicity.

Glaesserella parasuis is an important porcine pathogen that commonly colonizes the upper respiratory tract of pigs and is prone to causing Glässer's disease under complex conditions. As yet, the disease has led to serious economic losses to the swine industry worldwide. Studies so far have found that several virulence factors are associated with the pathogenicity of G. parasuis, but the pathogenic mechanism is still not fully understood. Cytolethal distending toxin (CDT), a potential virulence factor in G. parasuis, is involved in cytotoxicity, serum resistance, adherence to and invasion of host cells in vitro. Here, to further investigate the pathogenic role of CDT during G. parasuis infection in vitro and in vivo, a double cdt1 and cdt2 deletion mutant (Δcdt1Δcdt2) without selectable marker was first generated in G. parasuis JS0135 strain by continuous natural transformations and replica plating. Morphological observation and lactate dehydrogenase assay showed that the Δcdt1Δcdt2 mutant was defective in cytotoxicity. Additionally, the Δcdt1Δcdt2 mutant was more susceptible to phagocytosis caused by 3D4/2 macrophages compared to the wild-type JS0135 strain. Moreover, by focusing on clinical signs, necropsy, bacterial recovery and pathological observation, we found that the deletion of cdt1 and cdt2 genes led to a significant attenuation of virulence in G. parasuis. Taken together, these findings suggest that as an important virulence factor, CDT can significantly affect the pathogenicity of G. parasuis.

Gubra Amylin-NASH Diet Induced Nonalcoholic Fatty Liver Disease Associated with Histological Damage, Oxidative Stress, Immune Disorders, Gut Microbiota, and Its Metabolic Dysbiosis in Colon.

SCOPE: The overall changes of colon under nonalcoholic fatty liver disease (NAFLD) remain to be further elucidated. METHODS AND RESULTS: This study establishes a mouse model of NAFLD through a long-term Gubra Amylin-nonalcoholic steatohepatitis (NASH) diet (GAN diet). The results show that GAN diet significantly induces weight gain, liver steatosis, colonic oxidative stress, and lipid accumulation in blood, liver, and adipose tissue in mice. GAN feeding reduces the diversity of the gut microbiota, alters the composition and abundance of the gut microbiota, and leads to an increase in microbial metabolites such as long-chain fatty acids (LCFAs) and secondary bile acids (BAs), as well as a decrease in short-chain fatty acids (SCFAs). The RNA-seq and immunofluorescence results reveal that the GAN diet alters the expression of proteins and their coding genes involved in oxidative stress, immune response, and barrier function in colon tissue, such as lipocalin-2 (Lcn2, p < 0.05), heme oxygenase-1 (HO-1/Hmox1, p < 0.05), interferon-gamma (IFN-γ), and claudin-3/7. In addition, correlation analysis indicates a strong correlation between the changes in gut microbiota and lipid biomarkers. Additionally, the expression of immune related genes in colon tissue is related to the LCFAs produced by microbial metabolism. CONCLUSION: GAN-induced NAFLD is related to microbiota and its metabolic imbalance, oxidative stress, immune disorders, and impaired barrier function in colon.

Optimization of extended Kozak elements enhances recombinant proteins expression in CHO cells.

In eukaryotes, the localization of small ribosomal subunits to mRNA transcripts requires the translation of Kozak elements at the starting site. The sequence of Kozak elements affects the translation efficiency of protein synthesis. However, whether the upstream nucleotide of Kozak sequence affects the expression of recombinant proteins in Chinese hamster ovary (CHO) cells remains unclear. In order to find the optimal sequence to enhance recombinant proteins expression in CHO cells, -10 to +4 sequences around ATG in 100 CHO genes were compared, and the extended Kozak elements with different translation intensities were constructed. Using the classic Kozak element as control, the effects of optimized extended Kozak elements on the secreted alkaline phosphatase (SEAP) and human serum albumin (HSA) gene were studied. The results showed that the optimized extended Kozak sequence can enhance the stable expression level of recombinant proteins in CHO cells. Furthermore, it was found that the increased expression level of the recombinant protein was not related with higher transcription level. In summary, optimizing extended Kozak elements can enhance the expression of recombinant proteins in CHO cells, which contributes to the construction of an efficient expression system for CHO cells.

Dynamic Structural Fluxionality in a Planar Tetracoordinate Carbon Cluster Stabilized by Boron Ligands.

The design of boron-based molecular rotors stems from boron-carbon binary clusters containing multiple planar hypercoordinate carbons (phCs, such as C2B8). However, the design of boron-coordinated phCs is challenging due to boron's tendency to occupy hypercoordinate centers more than carbon. Although this challenge has been addressed, the designed clusters of interest have not exhibited dynamic fluxionality similar to that of the initial C2B8. To address this issue, we report a σ/π doubly aromatic CB2H5+ cluster, the first global minimum containing a boron-coordinated planar tetracoordinate carbon atom with dynamic fluxionality. Dynamics simulations show that two ligand H atoms exhibit alternate rotation, resulting in an intriguing dynamic fluxionality in this cluster. Electronic structure analysis reveals the flexible bonding positions of the ligand H atoms because they do not participate in π delocalized bonding nor bond to any other non-carbon atom, highlighting this rotational fluxionality. Unprecedentedly, the fluxional process involves not only the usual conversion of the number of bonding atoms, but also the type of bonding (3c π bonds ↔ 4c σ bonds), which is an uncommon fluxional mechanism. The cluster represents an effort to apply phC species to molecular machines.

Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

Pedigree analysis exploring the inconsistency between diverse phenotypes and testing criteria for germline TP53 mutations in Chinese women with breast cancer.

PURPOSE: In the present study, we addressed the inconsistency between the testing criteria and diverse phenotypes for germline TP53 mutation in patients with breast cancer in the Chinese population. METHOD: We proposed a new added item (synchronous or metachronous bilateral breast cancer) as one of the testing criteria (aimed at high-penetrance breast cancer susceptibility genes) and applied it for determining TP53 germline mutation status in 420 female patients with breast cancer using multigene panel-based next-generation sequencing, Sanger sequencing, and mass spectrometry. RESULTS: We found that 1.4% of patients carried a pathogenic or likely pathogenic germline TP53 mutation. Compared with BRCA mutation carriers (8.0%) and non-carriers (7.1%), TP53 mutation carriers (33.3%) developed breast cancer earlier. The majority of TP53 mutation carriers (66.7%) developed breast cancer after age 30 and had bilateral breast cancer (33.3%). Pedigree investigation of four TP53 carriers and a patient with a TP53 variant of unknown significance revealed that neither of their parents harbored the same mutations as the probands, indicating that the mutations might occur de novo. CONCLUSION: Our study revealed distinguishing features of TP53 carriers among Chinese women with breast cancer, which is inconsistent with the currently used testing criteria; therefore, the newly proposed testing criteria may be more appropriate.

Tobacco Use Behaviors and Associated Factors among Newly Diagnosed Tuberculosis Patients in Benin and Burkina Faso.

The objective of this study was to assess tobacco use (TU) behaviors among newly diagnosed pulmonary TB (PTB) patients and identify associated factors in Benin and Burkina Faso. A cross-sectional study was conducted in 20 randomly selected TB clinics. To ensure a representative study cohort, clinics were stratified during the sampling process. PTB patients were consecutively sampled in 20 of the clinics between 1 December 2021 and 30 September 2022. The study population comprised individuals aged 15 years and above who were newly diagnosed with PTB. Among the 1399 registered PTB patients, 564 (40.3%) reported a history of TU, including 392 (28.0%) current tobacco users and 172 ex-tobacco users. Cigarettes emerged as the predominant form of TU (86.2%), followed by smokeless tobacco (6.4%), and chicha smoking (2.6%). Factors independently associated with tobacco use were male gender (p < 0.001), being in Burkina Faso (p < 0.001), and an age of 25-59 years (p = 0.002). Our multicentric study reveals a substantial prevalence of tobacco use among TB patients, with cigarette smoking emerging as the predominant form. These findings underscore the imperative for implementing targeted cessation interventions within TB control programs. Special emphasis is warranted for male patients aged 25-59 years.

Current research of Assisted Reproductive Technology for women with early endometrial cancer and atypical endometrial hyperplasia after conservative treatment.

As the incidence of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) has been increasing, and has shown young trend. It is crucial to study the fertility-preserving treatment of endometrial lesions and fertility-promoting protocols. Age, obesity, and irregular ovulation are not only high-risk factors for endometrial lesions but also key factors affecting female fertility. Assisted reproductive technology (ART) can significantly improve pregnancy outcomes in patients with AEH and EC after conservative treatment. Based on the existing studies, this article reviews the progress of research on pregnancy outcomes of ART and its influencing factors in such patients. It helps physicians in providing optimal fertility guidance.

Glycerophospholipid metabolism changes association with ozone exposure.

Exposure to ozone (O3) has been associated with cardiovascular outcomes in humans, yet the underlying mechanisms of the adverse effect remain poorly understood. We aimed to investigate the association between O3 exposure and glycerophospholipid metabolism in healthy young adults. We quantified plasma concentrations of phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) using a UPLC-MS/MS system. Time-weighted personal exposures were calculated to O3 and co-pollutants over 4 time windows, and we employed orthogonal partial least squares discriminant analysis to discern differences in lipids profiles between high and low O3 exposure. Linear mixed-effects models and mediation analysis were utilized to estimate the associations between O3 exposure, lipids, and cardiovascular physiology indicators. Forty-three healthy adults were included in this study, and the mean (SD) time-weighted personal exposures to O3 was 9.08 (4.06) ppb. With shorter exposure durations, O3 increases were associated with increasing PC and lysoPC levels; whereas at longer exposure times, the opposite relationship was shown. Furthermore, two specific lipids, namely lysoPC a C26:0 and lysoPC a C17:0, showed significantly positive mediating effects on associations of long-term O3 exposure with pulse wave velocity and systolic blood pressure, respectively. Alterations in specific lipids may underlie the cardiovascular effects of O3 exposure.

Uncovering the Aggregation-Induced Emission Mechanisms of Phenoxazine and Phenothiazine Groups.

Molecules with both aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) properties are potential organic light-emitting diode materials; however, the AIE and TADF mechanisms are still debatable. In this work, four molecules incorporating carbazole (Cz), phenoxazine (PXZ), and phenothiazine (PTZ) as donor groups to the diphenylsulfone acceptor were investigated. The experiment results indicate that a molecule containing Cz exhibits solely TADF properties, whereas molecules containing PXZ and PTZ demonstrate both TADF and AIE characteristics. As for DPS-PTZ, the result indicates that the thin-film environment restricts molecular twisting, consequently reducing nonradiative decay, thereby attributing to the AIE property by density functional theory and molecular dynamics simulation. As for DPS-PXZ, the result suggests that the restricted access to a conical intersection in a singlet excited via an expansion in the C-S-C angle is the pivotal factor for the AIE characteristic. The C-S-C angle twist of DPS-PXZ is impeded in the aggregate state and resulted in luminescence. Understanding the mechanisms serves as a valuable guide for the development of new AIE systems, enabling their application in various practical domains.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Recent advances in the characterization of essential genes and development of a database of essential genes.

Over the past few decades, there has been a significant interest in the study of essential genes, which are crucial for the survival of an organism under specific environmental conditions and thus have practical applications in the fields of synthetic biology and medicine. An increasing amount of experimental data on essential genes has been obtained with the continuous development of technological methods. Meanwhile, various computational prediction methods, related databases and web servers have emerged accordingly. To facilitate the study of essential genes, we have established a database of essential genes (DEG), which has become popular with continuous updates to facilitate essential gene feature analysis and prediction, drug and vaccine development, as well as artificial genome design and construction. In this article, we summarized the studies of essential genes, overviewed the relevant databases, and discussed their practical applications. Furthermore, we provided an overview of the main applications of DEG and conducted comprehensive analyses based on its latest version. However, it should be noted that the essential gene is a dynamic concept instead of a binary one, which presents both opportunities and challenges for their future development.

Impact of Hematoma on Capsular Contracture: A Comparative Study of Smooth and Textured Implants in a Miniature Pig Model.

BACKGROUND: Capsular contracture is a significant complication following mammaplasty, with varying incidence rates and symptoms. The etiology of capsular contracture is multifactorial, with postoperative hematoma being recognized as a potential contributing factor. OBJECTIVES: The study aimed to investigate the impact of postoperative hematoma on capsular contracture following mammaplasty, utilizing pig models and modified biomechanical testing. It sought to compare the severity of capsular contracture between smooth and textured implants in the presence of hematoma, assess the biomechanical properties of the capsules, and explore the histological and molecular changes associated with the condition. METHODS: The study involved five female miniature pigs, implanted with both smooth and textured implants. Hematoma models were established, and various methods were employed to evaluate the impact of the prosthesis surface and hematoma on capsular contracture, including ultrasound assessment, biomechanical tests, scanning electron microscopy, histological analysis, and transcriptome sequencing. RESULTS: Capsules in hematoma groups were classified as Baker III/IV, with significantly unfavorable thickness, elastic modulus, and relaxation/creep amounts compared to non-hematoma groups. Smooth implants under hematoma conditions exhibited increased muscle content and biomechanical strength of the capsule. Transcriptomic analysis highlighted differential gene expression related to muscle development and contraction in smooth implants with hematomas. CONCLUSIONS: Hematomas increase the risk of capsular contracture, with smooth implants exacerbating this effect by enhancing pathways related to muscle development and contraction. This underscores the importance of hematoma prevention and treatment strategies, particularly when using smooth implants, to minimize the occurrence of capsular contracture. The study provides insights into the mechanisms underlying capsular contracture and offers evidence to guide surgical and postoperative management strategies.

Benefits of maternal pectin supplementation in gestation diet on vaginal microbiota of sows and intestinal health of newborn piglets.

Pectin is a proven prebiotic and widely used in human health products. This study aims to assess the impact of dietary pectin supplementation during gestation on sow vaginal microbiota and the offspring's intestinal composition. Thirty sows were randomly allocated to two groups and fed a standard diet (CON) or a standard diet supplemented with 3 g/kg pectin (PEC). Blood, feces, and vaginal swab samples from the sows and blood, intestines issue, and colonic content samples from the offspring were collected and analyzed. The results indicate that the relative abundance of vaginal Lactobacillus was notably enhanced in the PEC group and fecal ß-glucuronidase (ß-G) activity and plasma 17ß-estradiol (E2) concentration were also significantly increased in the PEC group. Newborn piglets were found to host different microbial communities as well. At the phylum level, Proteobacteria dominated in the CON group, and Firmicutes was predominant in the PEC group. Newborn piglets in the PEC group had a lower interleukin-6 (IL-6) concentration in their plasma. The expression of intestinal cytokines of offspring was improved as well. Villus height and villus height/crypt depth (V/C) in the PEC group were extremely higher than those in the CON group. In conclusion, dietary pectin supplementation can be of benefit to both sows and newborn piglets.

Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer.

PURPOSE: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer. METHODS: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3-4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. RESULTS: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. CONCLUSION: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.

A Gestational Pectin Diet Could Improve the Health of Multiparous Sows by Modulating the Gut Microbiota and Cytokine Level during Late Pregnancy.

This study aimed to investigate the effects of the dietary fiber pectin on the gut microbiota and health of parturient sows. A total of 30 parity 5-7, multiparous gestation sows (Large White × Landrace) were randomly assigned to two treatment groups after mating: Con (control, basic diet) and Pec (pectin, 3%). The sows received the two diets during gestation, and all sows were fed the same standard basic diet during lactation. The results of ß-diversity showed that the composition of the gut microbiota was different in the Con and Pec groups. Compared with the sows in the Con group, the Pec sows showed a higher abundance of the gut bacteria Clostridium and Romboutsia and a lower abundance of harmful bacteria (Micrococcaceae, Coriobacteriaceae, Dorea, Actinomyces). On the other hand, the SCFA plasma concentration was increased in the Pec group, while pro-inflammatory cytokine (IL-6, IL-1ß, and TNF-α) concentrations were decreased. In conclusion, the soluble dietary fiber pectin could improve the reproductive performance and health of sows by increasing the abundance of some commensal bacteria enhancing the metabolite SCFA levels and reducing the pro-inflammatory cytokine plasma levels.