Factor Xa inhibitors versus low-molecular-weight heparin for preventing coagulopathy following COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: Hospitalized patients with COVID-19 have shown a significant occurrence of thromboembolism and a heightened risk of death. It remains unclear whether factor Xa inhibitors are superior to enoxaparin in this context. Hence, there is a need for a direct comparison to assess the preventive effects and safety of factor Xa inhibitors versus enoxaparin in hospitalized COVID-19 patients. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) or retrospective studies that compared the effectiveness or safety of factor Xa inhibitors and enoxaparin in preventing thromboembolism in hospitalized patients with COVID-19. Embolic incidence, incidence of bleeding, and all-cause mortality were among the outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 percent CIs. Results: The analysis included six RCTs and two retrospective studies containing 4048 patients. Meta-analysis showed a statistically significant reduction among patients on factor Xa inhibitors compared with low-molecular-weight heparin (LMWH) in the embolic incidence [risk ratio (RR) 0.64 (95%, CI 0.42, 0.98); P=0.04, I2=12%]. Upon subgroup analysis by type of study design, no significant reductions were noted in patients on factor Xa inhibitors in RCTs (RR: 0.62; 95% CI: 0.33-1.17; P=0.14) or observational studies (RR: 0.53; 95% CI: 0.23-1.26; P=0.15) when compared with enoxaparin Factor Xa inhibitors were not significantly associated with incidence of bleeding [RR 0.76 (95% CI 0.36, 1.61); P=0.47, I2=0%] or all-cause mortality (RR: 0.81; 95% CI: 0.48-1.36; P=0.43). Consistent results were obtained upon subgroup analysis by the type of study design. Conclusion: Factor Xa inhibitors are more effective than enoxaparin in preventing thromboembolism among patients with COVID-19 who are not acutely ill and are hospitalized. Additional rigorous RCTs comparing factor Xa inhibitors with enoxaparin are warranted.

New insights into membrane fouling in coagulation-ultrafiltration by cake characteristics analysis: A case study with PACl-Al13 and PACl.

Membrane fouling is a bottleneck issue that hindered the further application of ultrafiltration technology. To alleviate membrane fouling, coagulation-ultrafiltration (C-UF) process using polyaluminum chloride (PACl) and PACl-Al13 with high proportion of Al13O4(OH)247+ as coagulants, respectively, were investigated at various pH conditions. Results indicated that an increase in solution pH contributed to larger floc size and looser floc structure for both PACl and PACl-Al13. It was conducive to the formation of more porous cake, as evidenced by mean pore area and pore area distribution of cake, leading to lower reversible fouling. Furthermore, humic acid (HA) removal presented a trend of first increasing and then decreasing with the increase of pH. The optimal HA removal was achieved at pH 6 regardless of coagulant type, suggesting that the slightest irreversible fouling should be occurred at this point. Interestingly, the irreversible fouling with PACl coagulant achieved a minimum value at pH 9, while the minimal irreversible fouling with PACl-Al13 was observed at pH 6. We speculated that the cake formed by PACl could further intercept HA prior to UF process at alkaline pH. Furthermore, compared with PACl, PACl-Al13 had a stronger charge neutralization ability, thus contributing to more compact floc structure and higher HA removal at various pH conditions. By UF fractionation measurement, higher HA removal for PACl-Al13 was due to higher removal of HA with molecular weight less than 50 kDa.

A retrospective study of the management and outcomes of pregnancies with inherited antithrombin deficiency.

INTRODUCTION: Antithrombin (AT) deficiency is a rare but highly thrombogenic inherited thrombophilia. Its association with adverse pregnancy outcomes (APO) is undefined. There is limited guidance on managing AT deficiency in pregnancy. Some significant issues remain controversial, including risk assessment for prophylactic anticoagulation, anticoagulant therapy, and monitoring. Our goal was to examine if the antepartum management of patients with AT deficiency affected their pregnancy outcomes. MATERIALS AND METHODS: This retrospective, single-center observational study included pregnant women with inherited AT deficiency in Peking Union Medical College Hospital between 2013 and 2024. RESULTS: Seventeen pregnancies in 6 women with AT deficiency were identified. A total of 7 pregnancies received adjusted-dose low-molecular-weight heparin (LMWH) and were monitored by anti-Xa level, AT activity, and D-dimer. There were 5 live births (all received LMWH), 7 second-trimester abortions (1 received LMWH), and 5 early pregnancy losses (1 received LMWH). There were 5 abruptio placentae events (3 received LMWH) and 7 thrombotic events (2 received LMWH). CONCLUSIONS: AT deficiency is at least an important partial factor contributing to APO. It is suggested to make a full assessment of AT patients both for venous thrombus embolism and APO risk. We observed a high prevalence of heparin resistance and a positive correlation between adequate anticoagulation and pregnancy outcome based on tight monitoring with anti-Xa level and timely adjustment of the LMWH dosage.

Low-molecular-weight heparin ameliorates intestinal barrier dysfunction in aged male rats via protection of tight junction proteins.

The intestinal barrier weakens and chronic gut inflammation occurs in old age, causing age-related illnesses. Recent research shows that low-molecular-weight heparin (LMWH), besides anticoagulation, also has anti-inflammatory and anti-apoptotic effects, protecting the intestinal barrier. This study aims to analyze the effect of LMWH on the intestinal barrier of old male rodents. This study assigned Sprague-Dawley male rats to four groups: young (3 months), young + LMWH, old (20 months), and old + LMWH. The LMWH groups received 1 mg/kg LMWH via subcutaneous injection for 7 days. Optical and transmission electron microscopy (TEM) were used to examine morphological changes in intestinal mucosa due to aging. Intestinal permeability was measured using fluorescein isothiocyanate (FITC)-dextran. ELISA kits were used to measure serum levels of IL-6 and IL-1ß, while Quantitative RT-PCR detected their mRNA levels in intestinal tissues. Western blotting and immunohistochemistry (IHC) evaluated the tight junction (TJ) protein levels such as occludin, zonula occludens-1 (ZO-1), and claudin-2. Western blotting assessed the expression of the apoptosis marker cleaved caspase 3, while IHC was used to detect LGR5+ intestinal stem cells. The intestinal permeability of aged rats was significantly higher than that of young rats, indicating significant differences. With age, the protein levels of occludin and ZO-1 decreased significantly, while the level of claudin-2 increased significantly. Meanwhile, our study found that the levels of IL-1ß and IL-6 increased significantly with age. LMWH intervention effectively alleviated age-related intestinal barrier dysfunction. In aged rats treated with LMWH, the expression of occludin and ZO-1 proteins in the intestine increased, while the expression of claudin-2 decreased. Furthermore, LMWH administration in aged rats resulted in a decrease in IL-1ß and IL-6 levels. LMWH also reduced age-related cleaved caspase3 expression, but IHC showed no difference in LGR5+ intestinal stem cells between groups. Research suggests that LMWH could potentially be a favorable therapeutic choice for age-related diseases associated with intestinal barrier dysfunction, by protecting TJ proteins, reducing inflammation, and apoptosis.

Long-Term Prevention of Biofilm Formation by Polycatechol-Based Supramolecular Assemblies with Low Molecular Weight Polymers on Surfaces.

Achievement of a stable surface coating with long-term resistance to biofilm formation remains a challenge. Catechol-based polymerization chemistry and surface deposition are used as tools for surface modification of diverse materials. However, the control of surface deposition of the coating, surface coverage, coating properties, and long-term protection against biofilm formation remain to be solved. We report a new approach based on supramolecular assembly to generate long-acting antibiofilm coating. Here, we utilized catechol chemistry in combination with low molecular weight amphiphilic polymers for the generation of such coatings. Screening studies with diverse low molecular weight (LMW) polymers and different catechols are utilized to identify lead compositions, which resulted in a thick coating with high surface coverage, smoothness, and antibiofilm activity. We have identified that small supramolecular assemblies (∼10 nm) formed from a combination of polydopamine and LMW poly(N-vinyl caprolactam) (PVCL) resulted in relatively thick coating (∼300 nm) with excellent surface coverage in comparison to other polymers and catechol combinations. The coating properties, such as thickness (10-300 nm) and surface hydrophilicity (with water contact angle: 20-60°), are readily controlled. The optimal coating composition showed excellent antibiofilm properties with long-term (>28 days) antibiofilm activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. We further utilized the combination of optimal binary coating with silver to generate a coating with sustained release of silver ions, resulting in killing both adhered and planktonic bacteria and preventing long-term surface bacterial colonization. The new coating method utilizing LMW polymers opens a new avenue for the development of a novel class of thick, long-acting antibiofilm coatings.

Gut microbiota-mediated metabolism of green tea catechins and the biological consequences: An updated review.

Multiple beneficial effects have been attributed to green tea catechins (GTCs). However, the bioavailability of GTCs is generally low, with only a small portion directly absorbed in the small intestine. The majority of ingested GTCs reaches the large intestinal lumen, and are extensively degraded via biotransformation by gut microbiota, forming many low-molecular-weight metabolites such as phenyl-γ-valerolactones, phenolic acids, butyrate, and acetate. This process not only improves the overall bioavailability of GTC-derived metabolites but also enriches the biological activities of GTCs. Therefore, the intra- and inter-individual differences in human gut microbiota as well as the resulting biological contribution of microbial metabolites are crucial for the ultimate health benefits. In this review, the microbial degradation of major GTCs was characterized and an overview of the in vitro models used for GTC metabolism was summarized. The intra- and inter-individual differences of human gut microbiota composition and the resulting divergence in the metabolic patterns of GTCs were highlighted. Moreover, the potential beneficial effects of GTCs and their gut microbial metabolites were also discussed. Overall, the microbial metabolites of GTCs with higher bioavailability and bioactive potency are key factors for the observed beneficial effects of GTCs and green tea consumption.

Preferences of pregnant women for postpartum thromboprophylaxis: the bicentric PREFER-PP study.

BACKGROUND: Clinical guidelines for postpartum thromboprophylaxis differ due its uncertain effect and varying preferences of experts. Women's preferences for postpartum thromboprophylaxis are unknown, although they may inform practices and future research. Our aim was to elicit the pregnant women's preferences for postpartum thromboprophylaxis, according to different risks of venous thromboembolism (VTE) and bleeding. METHODS: In two Swiss and French maternity hospitals, we conducted structured interviews of pregnant or postpartum women. Participants were instructed on pulmonary embolism (PE), deep vein thrombosis (DVT), postpartum hemorrhage (PPH) and subcutaneous injections of low-molecular-weight heparin (LMWH). First, we randomized women to either standard gamble or time trade-off (two different validated methods) to estimate the utilities (quality-of-life, from 0-1) of these health states. Second, we elicited the preference for the use of short-term postpartum thromboprophylaxis with LMWH vs. none across different risks of postpartum VTE and bleeding, through direct-choice exercises. RESULTS: Among 122 participants, median (IQR) health states utilities were 0.725 (0.30-0.925) for PE, 0.75 (0.40-0.97) for PPH, 0.85 (0.60-0.97) for DVT and 0.96 (0.96-0.999) for LMWH injections. The median risk of postpartum VTE to prefer the use of postpartum thromboprophylaxis over no treatment was 0.1% (IQR 0.01-0.50%) without LMWH-associated bleeding risk and 0.2% (IQR 0.1-5%) with a 1% bleeding risk. CONCLUSIONS: European pregnant women appear to have a high willingness for 10-day postpartum thromboprophylaxis, preferred over no treatment even for low risks of postpartum VTE. This perspective from patients supports the urgent need for a randomized trial evaluating the efficacy and safety of postpartum thromboprophylaxis.

Risk of developing post thrombotic syndrome after deep vein thrombosis with different anticoagulant regimens: A systematic review and pooled analysis.

BACKGROUND: Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens. METHODS: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software. RESULTS: A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively. CONCLUSIONS: The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC.

Damage Resistance of Kevlar® Fabric, UHMWPE, PVB Multilayers Subjected to Concentrated Drop-Weight Impact.

The impact resistance of layered polymer structures using polyvinyl butyral (PVB) in combination with Kevlar® fabric and ultra-high molecular weight polyethylene (UHMWPE) were fabricated and tested. Methods of wet impregnation and hot-press impregnation and consolidation of fabric with PVB and UHMWPE were used to manufacture multilayer constructs. All sandwich constructs were fixed to the surface of ballistic clay and subject to a free drop-weight test with a conical impactor having a small contact area. All tests were made at the same impact energy of 9.3 J and velocity of 2.85 m/s. The change in the resistance force was recorded using a piezoelectric force sensor at the time intervals of 40 µs. Using experimental force-time history, the change in the impactor's velocity, the depth of impactor penetration, the energy transformation at various stages of impactor interaction with the sample, and other parameters were obtained. Three indicators were considered as the main criteria for the effectiveness of a sample's resistance to impact: (1) minimum deformation, bulging, of the panel backside at the moment of impact, (2) minimum absorption of impact energy per areal density, and (3) minimal or, better yet, no destruction of structural integrity. Under the tested conditions, the rigid Kevlar-PVB-Kevlar sandwich at the frontside and relatively soft but flexible UHMWPE-Kevlar-UHMWPE layers in the middle helped to localize and absorb impact energy, while the backside Kevlar-PVB-Kevlar sandwich minimized local bulging providing the best overall performance. The front layer damage area was very shallow and less than two impactor tip diameters. The backside bulging was also less than in any other tested configurations.

Molecular-level insights into dissolved organic matter and its variations of the full-scale processes in a typical petrochemical wastewater treatment plant.

Petrochemical wastewater (PCWW) treatment poses challenges due to its unique and complex dissolved organic matter (DOM) composition, originating from various industrial processes. Despite the addition of advanced treatment units in PCWW treatment plants to meet discharge standards, the mechanisms of molecular-level sights into DOM reactivity of the upgraded full-scale processes including multiple biological treatments and advanced treatment remain unclear. Herein, we employ water quality indexes, spectra, molecular weight (MW) distribution, and Fourier transform ion cyclotron resonance mass spectrometry to systematically characterize DOM in a typical PCWW treatment plant including influent, micro-oxygen hydrolysis acidification (MOHA), anaerobic/oxic (AO), and micro-flocculation sand filtration-catalytic ozonation (MFSF-CO). Influent DOM is dominated by tryptophan-like and soluble microbial products with MW fractions 〈 1 kDa and 〉 100 kDa, and CHO with lignin and aliphatic/protein structures. MOHA effectively degrades macromolecular CHO (10.86 %) and CHON (5.24 %) compounds via deamination and nitrogen reduction, while AO removes CHOS compounds with MW < 10 kDa by desulfurization, revealing distinct DOM conversion mechanisms. MFSF-CO transforms unsaturated components to less aromatic and more saturated DOM through oxygen addition reactions and shows high CHOS and CHONS reactivity via desulfurization and deamination reactions, respectively. Moreover, the correlation among multiple parameters suggests UV254 combined with AImod as a simple monitoring indicator of DOM to access the chemical composition. The study provides molecular-level insights into DOM for the contribution to the improvement and optimization of the upgraded processes in PCWW.

Effects of Hydrolyzed Collagen as a Dietary Supplement on Fibroblast Activation: A Systematic Review.

BACKGROUND: Our objective was to conduct a systematic review of the effects of hydrolyzed collagen supplementation on the proliferation and activation of fibroblasts. METHODS: The search was conducted for journals that published articles in the English language, peer-reviewed, meeting the following criteria: (a) randomized clinical trials, (b) randomized studies in animals or humans, (c) in vitro studies, (d) studies using hydrolyzed collagens or collagen peptides, and (e) studies assessing alterations on fibroblasts as the primary or secondary outcome. We utilized the main journal databases PubMed/Web of Science and ongoing reviews by PROSPERO. For bias risk and methodological quality, we used an adaptation of the Downs and Black checklist. Our review followed the PRISMA checklist, conducted from February 2024 to the first week of March 2024, by two independent researchers (P.A.Q.I. and R.P.V.). RESULTS: Eleven studies were included in this review, where our findings reinforce the notion that hydrolyzed collagens or collagen peptides at concentrations of 50-500 µg/mL are sufficient to stimulate fibroblasts in human and animal tissues without inducing toxicity. Different enzymatic processes may confer distinct biological properties to collagens, allowing for scenarios favoring fibroblast promotion or antioxidant effects. Lastly, collagens with lower molecular weights exhibit greater bioavailability to adjacent tissues. CONCLUSIONS: Hydrolyzed collagens or collagen peptides with molecular sizes ranging from <3 to 3000 KDa promote the stimulation of fibroblasts in human tissues.

Effectiveness of topical hyaluronic acid of different molecular weights in xerosis cutis treatment in elderly: a double-blind, randomized controlled trial.

Dry skin is a common dermatological condition that frequently affects the elderly. A contributing cause to dry skin is a reduced concentration of hyaluronic acid (HA) in both the epidermis and dermis. The effectiveness of moisturizer containing HA as a therapy for dry skin is impacted by its specific molecular weight. Low molecular weight HA (LMWHA) is believed to be more effective in replenishing skin hydration in aging skin compared to High Molecular Weight HA (HMWHA) due to its ability to penetrate the stratum corneum. However, there is a lack of clinical research supporting this claim. A double-blind, randomized controlled trial was conducted on 36 residents of a nursing home in Jakarta. The participants, aged between 60 and 80 years, had been diagnosed with dry skin. Each test subject was administered three distinct, randomized moisturizing lotions (LMWHA, HMWHA, or vehicle), to be topically applied to three separate sites on the leg. Skin capacitance (SCap), transepidermal water loss (TEWL), and specified symptom sum score (SRRC) were measured at weeks 0, 2, and 4. After four weeks of therapy, area that was treated with LMWHA showed greater SCap values compared to the area treated with HMWHA (56.37 AU vs. 52.37 AU, p = 0.004) and vehicle (56.37 AU vs. 49.01 AU, p < 0.001). All groups did not show any significant differences in TEWL and SRRC scores. No side effects were found in all groups. The application of a moisturizer containing LMWHA to the dry skin of elderly resulted in significant improvements in skin hydration compared to moisturizers containing HMWHA and vehicle. Furthermore, these moisturizers demonstrated similar safety in treating dry skin in the elderly. ClinicalTrials.gov Identifier NCT06178367, https://clinicaltrials.gov/study/NCT06178367 .

Mechanochemical Tailoring of Lignin Structure: Influence of Different Particle Sizes in the Organosolv Process.

The autocatalyzed ethanolic organosolv process is gaining increasing attention for the sulfur-free isolation of lignin, which is subsequently used as a renewable substitute for various fossil-based applications. For the first time, the mechanochemical influence of seven different particle sizes of two different biomasses on the respective organosolv lignin structure is examined. Wine pruning (Pinot Noir) and wine pomace (Accent) are used for organosolv process with particle sizes ranging from 2.0-1.6 mm to less than 0.25 mm. As particle size decreases, the weight-average molecular weight increases, while the total phenol content decreases significantly. Additionally, the distribution of the lignin-typical monolignols and relevant substructures, as determined by two-dimensional heteronuclear nuclear magnetic resonance spectra single quantum coherence (HSQC), is observed. The degree of grinding of the biomass has a clear chemical-structural influence on the isolated HG and HGS organosolv lignins. Therefore, it is crucial to understand this influence to apply organosolv lignins in a targeted manner. In the future, particle size specifications in the context of the organosolv process should be expressed in terms of distribution densities rather than in terms of a smaller than specification.

Molecular weight-dependent differences in spectral properties and metal-binding behaviors of dissolved organic matter from different lakes.

Dissolved organic matter (DOM) plays an important role in governing metal speciation and migration in aquatic systems. In this study, various DOM samples were collected from Lakes Erhai, Kokonor, and Chaka, and size-fractionated into high molecular weight (HMW, 1 kDa-0.7 µm) and low molecular weight (LMW, <1 kDa) fractions for measurements of dissolved organic carbon (DOC), spectral properties, and metal binding behaviors. Our results demonstrated that samples from Lake Chaka exhibited the highest DOC concentration and fluorescence indices but the lowest percentage of carbohydrates. Regardless of sampling locations, the HMW-DOM fractions contained higher abundances of aromatic DOM, carbohydrates and protein-like substances, but lower abundance of fulvic acid-like substances compared to those in the LMW fractions. Metal titration experiments coupled with the excitation-emission matrix (EEM)-parallel factor (PARAFAC) modeling revealed that the quenching of the PARAFAC-derived fluorescent components was more pronounced in the presence of Cu(II) compared to Pb(II). Humic-like components emerged as a superior model, exhibiting higher binding affinities for Cu(II) than protein-like substances, while the opposite trend was observed for Pb(II). In samples obtained from Lakes Erhai and Kokonor, the condition stability constants (Log KM) for the binding of both Cu(II) and Pb(II) with the HMW-DOM fraction were higher than those with the LMW-DOM fraction. Conversely, a contrasting trend was observed for Lake Chaka. This study highlighted the heterogeneity in spectral properties and metal-binding behaviors of natural DOMs, contributing to an improved understanding of the molecular interactions between DOM components and metal ions and their environmental fate in aquatic ecosystems.

Effect of different amphiphilic emulsifiers complexed with xanthan gum on the stability of walnut milk and structural characterization of their complexes.

The kind of compounding emulsifier used and the amount of compounding have a significant impact on the emulsion's stability. In this study, the average particle size, Zeta potential, emulsification index, laser confocal microstructure, and rheological properties shows that the ratio of monoglyceride-xanthan gum and sucrose ester-xanthan gum could maintain the good stability of the emulsion in a certain range, and the monoglyceride and sucrose ester compounding could effectively improve the stability of the emulsion in a specific ratio (7:3). The results of fluorescence spectroscopy, Fourier transform infrared spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the simultaneous complexation of three substances was more likely to produce hydrophobic interactions with walnut proteins than the simultaneous complexation of two substances. Also confirmed were the hydrogen bonding connections between the proteins and the monoglyceride, sucrose ester, and xanthan gum. Monoglyceride and xanthan gum complexes were also found to stabilize more proteins.

Impact of molecular weight and gastrointestinal digestion on the immunomodulatory effects of Lycium barbarum polysaccharides.

In traditional Chinese medicine, Lycium barbarum is of rich medicinal value, and its polysaccharides are particularly interesting due to their significant pharmacological effects and potential health benefits. This study investigated the immunomodulatory effects of Lycium barbarum polysaccharides (LBPs) by examining their interaction with the TLR4/MD-2 complex and the impacts of gastrointestinal digestion on these interactions. We discovered that the affinity binding of LBPs for TLR4/MD-2 and their cytokine induction capability are influenced by molecular weight, with medium-sized LBPs (100-300 kDa) exhibiting stronger binding affinity and induction capability. Conversely, LBPs smaller than 10 kDa showed reduced activity. Additionally, the content of arabinose and galactose within the LBPs fractions was found to correlate positively with both receptor affinity and cytokine secretion. Simulated gastrointestinal digestion resulted in the degradation of LBPs into smaller fragments that are rich in glucose. Although these fragments exhibited decreased binding affinity to the TLR4/MD-2 complex, they maintained their activity to promote cytokine production. Our findings highlight the significance of molecular weight and specific monosaccharide composition in the immunomodulatory function of LBPs and emphasize the influence of gastrointestinal digestion on the effects of LBPs. This research contributes to a better understanding of the mechanisms underlying the immunomodulatory effects of traditional Chinese medicine polysaccharides and their practical application.

The proteome of Nicotiana benthamiana is shaped by extensive protein processing.

Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant proteins in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana, which has emerged as the main transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5040 plant proteins within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. This analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed processing events in vivo. This large proteomic dataset implicates an elaborate proteolytic machinery shaping the proteome of N. benthamiana.

Guideline-based venous thromboprophylaxis in postpartum women: An in-depth evaluation of ACOG and RCOG recommendations and real-life implementation

OBJECTIVES: Venous thromboembolism is one of the most serious complications of the postpartum period, and international societies have various thromboprophylaxis guidelines for its prevention. This study compares postpartum venous thromboprophylaxis recommendations from the American College of Obstetrics and Gynecology (ACOG) and the Royal College of Obstetricians and Gynecologists (RCOG) with real-life clinical practices. STUDY DESIGN: Data analysis of 1000 postpartum women at a tertiary care center focused on patient demographics, venous thromboembolism risk factors, and clinical thromboprophylaxis practices. Patient-specific risk factors were compared between ACOG and RCOG guidelines, assessing Low-Molecular-Weight-Heparin dosages and durations. Guideline compliance, undertreatment/overtreatment rates, and the required number of prefilled Low-Molecular-Weight-Heparin syringes were evaluated. RESULTS: Significant discrepancies were observed between ACOG and RCOG guidelines, particularly in Low Molecular Weight Heparin dosages and durations. Consensus rates with clinical approaches were around 53%, with inconsistencies leaning towards undertreatment (RCOG) and overtreatment (ACOG). The number of required prefilled Low-Molecular-Weight-Heparin syringes was notably higher according to RCOG compared to ACOG guidelines. CONCLUSION: Postpartum Venous thromboembolism prophylaxis guidelines from American College of Obstetrics and Gynecology and Royal College of Obstetricians and Gynecologists exhibit substantial differences, leading to variations in clinical practice. Further research on the significance of Venous thromboembolism risk factors is essential for improving risk assessment tools and refining guideline recommendations for pregnancy-related Venous thromboembolism prevention.

Quality control, safety assessment and preparation approaches of low molecular weight heparin.

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.

Investigating the Feasibility and Performance of Hybrid Overmolded UHMWPE 3D-Printed PEEK Structural Composites for Orthopedic Implant Applications: A Pilot Study.

Ultra-high-molecular-weight polyethylene (UHMWPE) components for orthopedic implants have historically been integrated into metal backings by direct-compression molding (DCM). However, metal backings are costly, stiffer than cortical bone, and may be associated with medical imaging distortion and metal release. Hybrid-manufactured DCM UHMWPE overmolded additively manufactured polyetheretherketone (PEEK) structural components could offer an alternative solution, but are yet to be explored. In this study, five different porous topologies (grid, triangular, honeycomb, octahedral, and gyroid) and three surface feature sizes (low, medium, and high) were implemented into the top surface of digital cylindrical specimens prior to being 3D printed in PEEK and then overmolded with UHMWPE. Separation forces were recorded as 1.97-3.86 kN, therefore matching and bettering the historical industry values (2-3 kN) recorded for DCM UHMWPE metal components. Infill topology affected failure mechanism (Type 1 or 2) and obtained separation forces, with shapes having greater sidewall numbers (honeycomb-60%) and interconnectivity (gyroid-30%) through their builds, tolerating higher transmitted forces. Surface feature size also had an impact on applied load, whereby those with low infill-%s generally recorded lower levels of performance vs. medium and high infill strategies. These preliminary findings suggest that hybrid-manufactured structural composites could replace metal backings and produce orthopedic implants with high-performing polymer-polymer interfaces.