Tailoring Drug Release Kinetics by the Design and Optimization of Substituents in Azobenzene Molecules in the Photosensitive Liposomal System.

A light-sensitive moiety, e.g., azobenzene, for the light-sensitive liposomal drug carrier has shown advantages as an advanced drug delivery system in site-specific smart therapy due to its reversible photoisomerization characteristics. In this work, a series of 4-position-cholesterol-functionalized azobenzene derivatives with 4'-position substituted pyridine, quinoline, isoquinoline, triethylamine, or ethylenediamine were synthesized, and the relationship between the molecular structure and drug release behaviors was clarified. We found that the charge and electrophilicity of substituents were two important factors (expressed as the characteristic time) that can precisely regulate the isomerization ratio in the liposomal system. There was an approximately linear correlation between the characteristic time of photoisomerization and the fitted first-order constant of photoinduced drug release rate. The photoinduced drug release could be achieved at the desired time and in an appropriate amount by tailoring the substituents at the 4'-position of azobenzene-cholesterol derivatives.

Safety of low-intensity extracorporeal shock wave therapy in prostate disorders: in vitro and in vivo evidence.

ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model (n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [γ-H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Advances in meniscus tissue engineering: Towards bridging the gaps from bench to bedside.

Meniscus is vital for maintaining the anatomical and functional integrity of knee. Injuries to meniscus, commonly caused by trauma or degenerative processes, can result in knee joint dysfunction and secondary osteoarthritis, while current conservative and surgical interventions for meniscus injuries bear suboptimal outcomes. In the past decade, there has been a significant focus on advancing meniscus tissue engineering, encompassing isolated scaffold strategies, biological augmentation, physical stimulus, and meniscus organoids, to improve the prognosis of meniscus injuries. Despite noteworthy promising preclinical results, translational gaps and inconsistencies in the therapeutic efficiency between preclinical and clinical studies exist. This review comprehensively outlines the developments in meniscus tissue engineering over the past decade (Scheme 1). Reasons for the discordant results between preclinical and clinical trials, as well as potential strategies to expedite the translation of bench-to-bedside approaches are analyzed and discussed.

Evaluating the significance of ECSCR in the diagnosis of ulcerative colitis and drug efficacy assessment.

Background: The main challenge in diagnosing and treating ulcerative colitis (UC) has prompted this study to discover useful biomarkers and understand the underlying molecular mechanisms. Methods: In this study, transcriptomic data from intestinal mucosal biopsies underwent Robust Rank Aggregation (RRA) analysis to identify differential genes. These genes intersected with UC key genes from Weighted Gene Co-expression Network Analysis (WGCNA). Machine learning identified UC signature genes, aiding predictive model development. Validation involved external data for diagnostic, progression, and drug efficacy assessment, along with ELISA testing of clinical serum samples. Results: RRA integrative analysis identified 251 up-regulated and 211 down-regulated DEGs intersecting with key UC genes in WGCNA, yielding 212 key DEGs. Subsequently, five UC signature biomarkers were identified by machine learning based on the key DEGs-THY1, SLC6A14, ECSCR, FAP, and GPR109B. A logistic regression model incorporating these five genes was constructed. The AUC values for the model set and internal validation data were 0.995 and 0.959, respectively. Mechanistically, activation of the IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway in UC was indicated by KEGG and GSVA analyses, which were positively correlated with the signature biomarkers. Additionally, the expression of the signature biomarkers was strongly correlated with various UC types and drug efficacy in different datasets. Notably, ECSCR was found to be upregulated in UC serum and exhibited a positive correlation with neutrophil levels in UC patients. Conclusions: THY1, SLC6A14, ECSCR, FAP, and GPR109B can serve as potential biomarkers of UC and are closely related to signaling pathways associated with UC progression. The discovery of these markers provides valuable information for understanding the molecular mechanisms of UC.

Dose-response relationship between physical activity and frailty: A systematic review and meta-analysis.

Objective: Frailty is a significant public health issue facing aging societies and can be reduced by physical activity (PA), but the dose-response relationship between PA and frailty is not clear. This systematic review and dose-response meta-analysis aimed to assess the effect of PA on frailty in adults by aggregating data from observational studies. Methods: PubMed, Embase, Web of Science, Cochrane Library, Scopus, SAGE Reference Online, SinoMed, CINAHL and CNKI were retrieved for articles published before May 2024. After quality evaluation, data on PA and the risk of frailty were extracted. Stata/MP 17.0 was used for dose-response meta-analysis. Results: A total of 15 articles were included, involving 34,754 participants, including 4250 subjects with frailty or pre-frailty. The consequence of the dose-response meta-analysis revealed that compared with those who were not active at all, a 22 % (95 % CI, 16 %-28 %) reduction in the risk of frailty in individuals with 11.25 MET h/week of cumulative activity and a 55 % (95 % CI, 44 %-63 %) reduction in the risk of frailty in those with 22.5 MET h/week of cumulative activity; for higher activity levels (36.75 MET h/week), the risk of frailty was reduced by 68 % (95 % CI, 58 %-76 %) and continued to be reduced as PA volum increased. Conclusions: There is a non-linear dose-response relationship between PA and frailty risk. Even small amounts of PA could reduce the risk of frailty. Meeting the minimum recommended PA target could reduce some risks, and doubling the recommended PA volumes could reduce most risks, which continue to increase as the volum of PA accumulates.

Facilitating giant panda crossings of national highway in Wolong area of Giant Panda National Park amid human activities.

As human activities continue to expand, wildlife persistence faces escalating threats from roads. In Wolong area of Giant Panda National Park, the local giant pandas (Ailuropoda melanoleuca) are divided into two population groups along the National Highway G350 (NHG). Therefore, selecting suitable areas to help those giant pandas communicate across the NHG is necessary. In this research, we evaluated the presence of human activities and simulated their absence to analyze how they affect the giant panda's habitat in Wolong. Subsequently, based on the kernel density estimation (KDE) for giant pandas and the main human distribution locations, we selected suitable areas for the population link between the two road sections on the NHG. We simulated the absence of human activities on the two road sections to compare changes in the habitat suitability index (HSI) and connectivity value (CV) relative to their presence. We aimed to carefully select the area for future giant panda corridor plans and simulate whether eliminating human activities will significantly improve the HSI and CV of the area. Our results show that: (1) Human activities presence has led to subtle changes in the landscape pattern of suitable habitats and a decrease in Wolong by 78.76 km2 compared to their absence. (2) Human activities presence significantly reduced HSI and CV in the 1000 m buffer along the NHG compared to their absence. (3) The HSI and CV of the 1000 m buffer in the simulated absence of human activities for the two road sections were significantly higher than their presence. This research identified the optimal road section for crossing the NHG to link giant panda population groups and habitats in Wolong. These insights are significant for formulating conservation decisions and corridor plans and for promoting wildlife conservation in reserves amid high levels of human activity.

Blocking Aδ- and C-fiber neural transmission by sub-kilohertz peripheral nerve stimulation.

Introduction: We recently showed that sub-kilohertz electrical stimulation of the afferent somata in the dorsal root ganglia (DRG) reversibly blocks afferent transmission. Here, we further investigated whether similar conduction block can be achieved by stimulating the nerve trunk with electrical peripheral nerve stimulation (ePNS). Methods: We explored the mechanisms and parameters of conduction block by ePNS via ex vivo single-fiber recordings from two somatic (sciatic and saphenous) and one autonomic (vagal) nerves harvested from mice. Action potentials were evoked on one end of the nerve and recorded on the other end from teased nerve filaments, i.e., single-fiber recordings. ePNS was delivered in the middle of the nerve trunk using a glass suction electrode at frequencies of 5, 10, 50, 100, 500, and 1000 Hz. Results: Suprathreshold ePNS reversibly blocks axonal neural transmission of both thinly myelinated Aδ-fiber axons and unmyelinated C-fiber axons. ePNS leads to a progressive decrease in conduction velocity (CV) until transmission blockage, suggesting activity-dependent conduction slowing. The blocking efficiency is dependent on the axonal conduction velocity, with Aδ-fibers efficiently blocked by 50-1000 Hz stimulation and C-fibers blocked by 10-50 Hz. The corresponding NEURON simulation of action potential transmission indicates that the disrupted transmembrane sodium and potassium concentration gradients underly the transmission block by the ePNS. Discussion: The current study provides direct evidence of reversible Aδ- and C-fiber transmission blockage by low-frequency (<100 Hz) electrical stimulation of the nerve trunk, a previously overlooked mechanism that can be harnessed to enhance the therapeutic effect of ePNS in treating neurological disorders.

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

Ptycho-endoscopy on a lensless ultrathin fiber bundle tip.

Synthetic aperture radar (SAR) utilizes an aircraft-carried antenna to emit electromagnetic pulses and detect the returning echoes. As the aircraft travels across a designated area, it synthesizes a large virtual aperture to improve image resolution. Inspired by SAR, we introduce synthetic aperture ptycho-endoscopy (SAPE) for micro-endoscopic imaging beyond the diffraction limit. SAPE operates by hand-holding a lensless fiber bundle tip to record coherent diffraction patterns from specimens. The fiber cores at the distal tip modulate the diffracted wavefield within a confined area, emulating the role of the 'airborne antenna' in SAR. The handheld operation introduces positional shifts to the tip, analogous to the aircraft's movement. These shifts facilitate the acquisition of a ptychogram and synthesize a large virtual aperture extending beyond the bundle's physical limit. We mitigate the influences of hand motion and fiber bending through a low-rank spatiotemporal decomposition of the bundle's modulation profile. Our tests demonstrate the ability to resolve a 548-nm linewidth on a resolution target. The achieved space-bandwidth product is ~1.1 million effective pixels, representing a 36-fold increase compared to that of the original fiber bundle. Furthermore, SAPE's refocusing capability enables imaging over an extended depth of field exceeding 2 cm. The aperture synthesizing process in SAPE surpasses the diffraction limit set by the probe's maximum collection angle, opening new opportunities for both fiber-based and distal-chip endoscopy in applications such as medical diagnostics and industrial inspection.

Synergistic effects of PARP inhibition and cholesterol biosynthesis pathway modulation.

An in-depth multi-omic molecular characterisation of poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase (PARP) inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula®) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signalling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of a LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing of cancer cells to levels comparable to Niraparib as single agent. In addition, the combination of PARP inhibitors and statins, inhibitors of HMGCR, an enzyme catalysing the rate-limiting step in the mevalonate pathway, had a synergistic effect on tumor cell killing in cell lines and patient-derived ovarian tumor organoids. These observations suggest that concomitant inhibition of cholesterol biosynthesis pathway and PARP activity might result in stronger efficacy of these inhibitors against tumor types highly dependent on cholesterol metabolism.

Cyrtomiumadenotrichum (Dryopteridaceae), a new species from Guangxi, China.

Cyrtomiumadenotrichum Y. Nong & R.H. Jiang (Dryopteridaceae), a new species from Guangxi, China, is described and illustrated. This new species is similar to C.nephrolepioides (Christ) Copel., C.obliquum Ching & K. H. Shing ex K. H. Shing, C.sinningense Ching & K. H. Shing ex K. H. Shing and C.calcis Liang Zhang, N.T.Lu & Li Bing Zhang in having erect rhizomes, dense, leathery lamina and rounded sori, but it can be easily distinguishable by its stipe sparsely glandular, base obvious oblique, basiscopic base truncate, acroscopic base auriculate or ovate.

Prognostic significance of LRPPRC and its association with immune infiltration in liver hepatocellular carcinoma.

BACKGROUND: Leucine rich pentatricopeptide repeat containing (LRPPRC) protein is a multifunctional protein involved in cell cycle progression and tumor development. However, its prognostic significance and association with immune infiltration in Liver hepatocellular carcinoma (LIHC) remain unclear. METHODS: We utilized transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases of LIHC patients to investigate the potential pro-cancer role of LRPPRC, including differential expression of LRPPRC in LIHC, prognostic value, clinicopathological features, immune cell infiltration relevance and function enrichment analysis. RESULTS: Our findings suggest that LRPPRC is upregulated in LIHC and exhibits correlations with survival, clinical stage, and tumor grade in LIHC patients. Additionally, immune infiltration analysis revealed significant negative correlations between LRPPRC expression and multiple tumor-infiltrating immune cells, including CTLs, DCs, pDCs, B cells, Th17 cells, neutrophils, T cells, Mast cells, Th1 cells, Tregs, and NK cells, whereas a significant positive correlation was observed with infiltration of Th2 cells, T helper cells and Tcms. Furthermore, functional enrichment analysis indicated that LRPPRC may be involved in G2m checkpoint, mitotic spindle, E2f targets, Wnt Beta catenin signaling, spermatogenesis and other processes.

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.

iProps: A comprehensive software tool for protein classification and analysis with automatic machine learning capabilities and model interpretation capabilities.

Protein classification is a crucial field in bioinformatics. The development of a comprehensive tool that can perform feature evaluation, visualization, automated machine learning, and model interpretation would significantly advance research in protein classification. However, there is a significant gap in the literature regarding tools that integrate all these essential functionalities. This paper presents iProps, a novel Python-based software package, meticulously crafted to fulfill these multifaceted requirements. iProps is distinguished by its proficiency in feature extraction, evaluation, automated machine learning, and interpretation of classification models. Firstly, iProps fully leverages evolutionary information and amino acid reduction information to propose or extend several numerical protein features that are independent of sequence length, including SC-PSSM, ORDip, TRC, CTDC-E, CKSAAGP-E, and so forth; at the same time, it also implements the calculation of 17 other numerical features within the software. iProps also provides feature combination operations for the aforementioned features to generate more hybrid features, and has added data balancing sampling processing as well as built-in classifier settings, among other functionalities. Thus, It can discern the most effective protein class recognition feature from a multitude of candidates, utilizing three automated machine learning algorithms to identify the most optimal classifiers and parameter settings. Furthermore, iProps generates a detailed explanatory report that includes 23 informative graphs derived from three interpretable models. To assess the performance of iProps, a series of numerical experiments were conducted using two well-established datasets. The results demonstrated that our software achieved superior recognition performance in every case. Beyond its contributions to bioinformatics, iProps broadens its applicability by offering robust data analysis tools that are beneficial across various disciplines, capitalizing on its automated machine learning and model interpretation capabilities. As an open-source platform, iProps is readily accessible and features an intuitive user interface, ensuring ease of use for individuals, even those without a background in programming. The source code of the software is available for download at the following website: https://github.com/LigosQ/iProps and https://gitee.com/LigosQ/iProps.

Maternal Vitamin D3 Supplementation in an Oxidized-Oil Diet Protects Fetus from Developmental Impairment and Ameliorates Oxidative Stress in Mouse Placenta and Fetus.

BACKGROUND: Fried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. OBJECTIVES: This study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. METHODS: Pregnant mice were randomly assigned into 3 groups: Control group (diet with fresh soybean oil), OSO group [diet with oxidized soybean oil (OSO)], and OSOV group (diet with OSO and 10,000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. RESULTS: Maternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase, and inducible nitric oxide synthase, whereas VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor in the placenta. CONCLUSIONS: Maternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VD receptor/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics.

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.

Incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated haemophilia A.

INTRODUCTION: Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by lack or deficiency of coagulation factor VIII. AIM: The aim of this study is to determine the incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated persons with HA. METHODS: A total of 151 HA who underwent 221 major orthopaedic surgical procedures after intensive FVIII treatment were reviewed. The results of inhibitor tests were collected. Potential clinical risk factors for inhibitor development were analyzed. RESULTS: 111 people were diagnosed with severe HA. Thirty-seven persons (24.5%) had history of previous intensive FVIII treatment for surgical procedure. They received a mean perioperative cumulative FVIII of 498 iu/kg within first week after surgery. Seven cases (4.6%) developed an inhibitor post-operatively in our study. Surgical procedure for pseudotumor and the group of persons who experienced postoperative complications had the higher incidence of inhibitor development (9.5%, 13.3% respectively). Only previous history for intensive FVIII exposure was considered as a significant predictor for postoperative inhibitor development after multivariate logistic regression analysis (OR: 29.5, P = 0.002). CONCLUSION: The incidence of inhibitor development in previously treated persons with HA undergoing major orthopaedic surgery was 4.6% and the history of previous intensive FVIII treatment for surgery was associated with higher risk of inhibitor development.

Improvement of insulin sensitivity by dietary fiber consumption during late pregnant sows is associated with gut microbiota regulation of tryptophan metabolism.

BACKGROUND: Dietary fiber (DF) consumption was reported to improve insulin sensitivity, change the tryptophan metabolism, and alter the gut microbiota. Herein, this study aimed to investigate the effects of DF consumption on insulin sensitivity, tryptophan metabolism, and gut microbiota composition in sows during late pregnancy, and explore the relationship between tryptophan metabolites and insulin sensitivity regulated by DF supplementation. RESULTS: Twelve sows were randomly assigned to two dietary treatment groups (six/group): the low-fiber (LF) group, which was fed a basal diet, and the high-fiber (HF) group, which was fed the basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose. During late pregnancy, meal test, glucose tolerance test, and insulin challenge test were used to investigate the insulin sensitivity of sows, using the percutaneous brachiocephalic vein catheterization technique. High DF consumption resulted in improved insulin sensitivity, especially during the second and third trimesters, and promoted serotonin production from tryptophan. Additionally, plasma serotonin concentration was positively correlated with the insulin sensitivity index during late pregnancy. Moreover, DF consumption elevated fecal short-chain fatty acid (SCFA) concentrations, altered fecal microbial diversity, and increased the abundances of Rikenellaceae_RC9_gut_group, Alloprevotella, Parabacteroides, Roseburia, and Sphaerochaeta, which were positively correlated to plasma serotonin concentration. CONCLUSIONS: DF consumption improved insulin sensitivity during late pregnancy in sows, which improved microbial diversity in fecal samples and increased fecal SCFA concentrations, resulting in a positive correlation with plasma serotonin level.

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.