Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

Accelerating PROTACs Discovery Through a Direct-to-Biology Platform Enabled by Modular Photoclick Chemistry.

Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design-synthesis-evaluation process involving numerous cycles of labor-intensive synthesis-purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct-to-biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell-based bioassays without the need for additional purification. By integrating amide coupling and light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) photoclick chemistry into a plate-based synthetic process, this strategy produces PROTAC libraries with high efficiency and structural diversity. Moreover, by employing this platform for PROTACs screening, we smoothly found potent PROTACs effectively inhibit triple-negative breast cancer (TNBC) cell growth and induce rapid, selective targeted degradation of cyclin-dependent kinase 9 (CDK9). The study introduces a versatile platform for assembling PROTACs on plates, followed by direct biological evaluation. This approach provides a promising opportunity for high-throughput synthesis of PROTAC libraries, thereby enhancing the efficiency of exploring chemical space and accelerating the discovery of PROTACs.

Relationship Between Two Years of Muscle Strength Decrease and Volume Loss of Menisci and Cartilage According to Knee Pain in Mild and Moderate Knee Osteoarthritis.

OBJECTIVE: To explore the relationship between two-year changes in muscle strength and cartilage according to knee pain in mild and moderate knee Osteoarthritis (OA). DESIGN: 279 participants were retrospectively obtained from the Osteoarthritis Initiative. Western Ontario McMaster University (WOMAC) and Knee Injury and Osteoarthritis Outcome Score were used to assess pain and function. Five muscles strength (maximum extensor and flexor, normalized maximum extensor and flexor, and extensor/flexor ratio) were measured from isometric strength test. Menisci and cartilage volumes were measured from MRI to assess two-year of OA progression. RESULTS: Mild and moderate knee OA progression was characterized by patellofemoral cartilage loss and meniscal degeneration. For WOMAC pain >2 participants, decrease in extensor strength and normalized extensor strength were positively correlated with medial meniscus volume loss (r = 0.261, P = 0.021; r = 0.232, P = 0.041, respectively). The extensor/flexor ratio changes were positively associated with WOMAC function changes (r = 0.291, P = 0.013) over two-year. CONCLUSION: The study observed a positive correlation between quadriceps strength decrease and medial meniscus degeneration in mild and moderate knee OA patients with WOMAC pain >2. These findings suggested quadriceps-hamstrings balance possibly plays a protective role in knee function for participants with weaker quadriceps and severe pain.

Full-length radiograph based automatic musculoskeletal modeling using convolutional neural network.

Full-length radiographs contain information from which many anatomical parameters of the pelvis, femur, and tibia may be derived, but only a few anatomical parameters are used for musculoskeletal modeling. This study aimed to develop a fully automatic algorithm to extract anatomical parameters from full-length radiograph to generate a musculoskeletal model that is more accurate than linear scaled one. A U-Net convolutional neural network was trained to segment the pelvis, femur, and tibia from the full-length radiograph. Eight anatomic parameters (six for length and width, two for angles) were automatically extracted from the bone segmentation masks and used to generate the musculoskeletal model. Sørensen-Dice coefficient was used to quantify the consistency of automatic bone segmentation masks with manually segmented labels. Maximum distance error, root mean square (RMS) distance error and Jaccard index (JI) were used to evaluate the geometric accuracy of the automatically generated pelvis, femur and tibia models versus CT bone models. Mean Sørensen-Dice coefficients for the pelvis, femur and tibia 2D segmentation masks were 0.9898, 0.9822 and 0.9786, respectively. The algorithm-driven bone models were closer to the 3D CT bone models than the scaled generic models in geometry, with significantly lower maximum distance error (28.3 % average decrease from 24.35 mm) and RMS distance error (28.9 % average decrease from 9.55 mm) and higher JI (17.2 % average increase from 0.46) (P < 0.001). The algorithm-driven musculoskeletal modeling (107.15 ± 10.24 s) was faster than the manual process (870.07 ± 44.79 s) for the same full-length radiograph. This algorithm provides a fully automatic way to generate a musculoskeletal model from full-length radiograph that achieves an approximately 30 % reduction in distance errors, which could enable personalized musculoskeletal simulation based on full-length radiograph for large scale OA populations.

The second complete mitochondrial genome of Capillidium rhysosporum within the family Capillidiaceae, Entomophthorales.

The complete mitochondrial genome of the entomophthoroid fungus Capillidium rhysosporum (strain no.: ATCC 12588) was sequenced using next-generation sequencing technology. The assembled circular genome has a length of 46,756 base pairs with a GC content of 27.06%. Gene prediction identified 15 core protein-coding genes (PCGs), two rRNA genes, and 27 tRNA genes. Phylogenetic analysis confirmed that C. rhysosporum belongs to the Zoopagomycota clade and is closely related to C. heterosporum. This study presents the second complete mitochondrial genome within the family Capillidiaceae, contributing to the mitochondrial DNA database of entomophthoroid fungi.

High immigration rates critical for establishing emigration-driven diversity in microbial communities.

Unraveling the mechanisms governing the diversity of ecological communities is a central goal in ecology. Although microbial dispersal constitutes an important ecological process, the effect of dispersal on microbial diversity is poorly understood. Here, we sought to fill this gap by combining a generalized Lotka-Volterra model with experimental investigations. Our model showed that emigration increases the diversity of the community when the immigration rate crosses a defined threshold, which we identified as Ineutral. We also found that at high immigration rates, emigration weakens the relative abundance of fast-growing species and thus enhances the mass effect and increases the diversity. We experimentally confirmed this finding using co-cultures of 20 bacterial strains isolated from the soil. Our model further showed that Ineutral decreases with the increase of species pool size, growth rate, and interspecies interaction. Our work deepens the understanding of the effects of dispersal on the diversity of natural communities.

Coagulation performance and mechanism analysis of humic acid by using covalently bonded coagulants: effect of pH and matching mechanism of humic acid functional groups.

Conventional inorganic coagulants (Al, Fe) and Al/Fe-based covalently bonded flocculants (CAFMs) had different hydrolysis species at different pHs, which subsequently led to differences in their binding sites and complexation ability with humic acid (HA). Studying the binding sites and interactions between CAFMs, AlCl3 (Al), and FeCl3 (Fe) hydrolysates and HA molecules is critical to understanding the coagulation mechanism. The results found that CAFM 0.6, Al, and AlCl3 combined FeCl3 (Al/Fe) removed more than 90% of HA at pH 6, and CAFMs showed higher HA removal rate than that of Al, Fe, and Al/Fe under the same reaction conditions. The flocs of CAFMs contained abundant -NH2/OH as well as the large particle size, compact structure, and excellent settling performance. The hydrolyzed species of Al and Fe were predominantly Alb and Feb at pH 6, but the hydrolyzed species of CAFMs were primarily (Al + Fe)c. Moreover, the hydrolyzed species of Al and Al/Fe were found to complex with HA functional groups such as -COOH, C = O, C-H/C-C, C = C, and C-OH to form ligand bonds, while the hydrolyzed species (Al + Fe)c of CAFMs could deeply interact with HA functional groups including C-O, -COOH, C = O, C-H/C-C, C = C, and C-OH by the adsorption and sweeping.

Analysis of Nonhomologous End Joining and Homologous Recombination Efficiency in HEK-293T Cells using GFP Based Reporter Systems.

DNA double-strand breaks (DSBs) represent the most perilous DNA lesions, capable of inducing substantial genetic information loss and cellular demise. In response, cells employ two primary mechanisms for DSB repair: nonhomologous end joining (NHEJ) and homologous recombination (HR). Quantifying the efficiency of NHEJ and HR separately is crucial for exploring the relevant mechanisms and factors associated with each. The NHEJ assay and HR assay are established methods used to measure the efficiency of their respective repair pathways. These methods rely on meticulously designed plasmids containing a disrupted green fluorescent protein (GFP) gene with recognition sites for endonuclease I-SceI, which induces DSBs. Here, we describe the extrachromosomal NHEJ assay and HR assay, which involve co-transfecting HEK-293T cells with EJ5-GFP/DR-GFP plasmids, an I-SceI expressing plasmid, and an mCherry expressing plasmid. Quantitative results of NHEJ and HR efficiency are obtained by calculating the ratio of GFP-positive cells to mCherry-positive cells, as counted by flow cytometry. In contrast to chromosomally integrated assays, these extrachromosomal assays are more suitable for conducting comparative investigations involving multiple established stable cell lines.

Sprayable Zwitterionic Antibacterial Hydrogel With High Mechanical Resilience and Robust Adhesion for Joint Wound Treatment.

Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate-co-dopamine methacrylamide)-modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB-PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15-38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH-responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing.

The Effects of Long-Term Walking Exercise on Structural Progression, Symptoms, and Extensor Muscle Strength in Patients with Mild or at High Risk of Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

OBJECTIVE: To assess the relationship between walking exercise and medial joint space narrowing (JSN) progression, symptoms, and knee extensor muscle strength (EMS) in early knee osteoarthritis (OA) patients. METHODS: This nested cohort study within the Osteoarthritis Initiative included participants aged 50 and above with knee OA (Kellgren-Lawrence grades 0-2). Walking exercisers were identified using a modified Historical Physical Activity Survey Instrument. Differences in medial JSN, Knee Injury and Osteoarthritis Outcome Score (KOOS), and knee EMS were evaluated through the three-way ANOVA. RESULTS: Among 896 participants, 83.4% reported walking exercise. Female walkers showed significant improvements in symptoms (KOOS-Pain: P < 0.001; KOOS-Symptom: P < 0.001; KOOS-Quality of Life (QOL): P < 0.001; KOOS-Function, Sports, and Recreational Activities (FSR): P = 0.007). Similar results were observed in male walkers (KOOS-Pain: P < 0.001; KOOS-Symptom: P < 0.001; KOOS- QOL: P = 0.001; KOOS- FSR: P = 0.009). Walkers showed significantly increased knee EMS at 24 months (Female: P < 0.001; Male: P = 0.003). Female non-walkers had significantly decreased knee EMS at 24 months (P < 0.001). Walkers showed significant improvement in medial JSN (OR = 1.1, 95% CI: 1.0 to 1.2) and KL grade (OR = 1.0, 95% CI: 1.0 to 1.1) compared to non-walkers. CONCLUSION: Walking exercise prevents structural progression and improves symptoms. Meanwhile, the increased knee EMS in all walkers further supports the validity of recommending walking exercises for early-stage knee OA patients.

AlmA involved in the long-chain n-alkane degradation pathway in Acinetobacter baylyi ADP1 is a Baeyer-Villiger monooxygenase.

Many Acinetobacter species can grow on n-alkanes of varying lengths (≤C40). AlmA, a unique flavoprotein in these Acinetobacter strains, is the only enzyme proven to be required for the degradation of long-chain (LC) n-alkanes, including C32 and C36 alkanes. Although it is commonly presumed to be a terminal hydroxylase, its role in n-alkane degradation remains elusive. In this study, we conducted physiological, biochemical, and bioinformatics analyses of AlmA to determine its role in n-alkane degradation by Acinetobacter baylyi ADP1. Consistent with previous reports, gene deletion analysis showed that almA was vital for the degradation of LC n-alkanes (C26-C36). Additionally, enzymatic analysis revealed that AlmA catalyzed the conversion of aliphatic 2-ketones (C10-C16) to their corresponding esters, but it did not conduct n-alkane hydroxylation under the same conditions, thus suggesting that AlmA in strain ADP1 possesses Baeyer-Villiger monooxygenase (BVMO) activity. These results were further confirmed by bioinformatics analysis, which revealed that AlmA was closer to functionally identified BVMOs than to hydroxylases. Altogether, the results of our study suggest that LC n-alkane degradation by strain ADP1 possibly follows a novel subterminal oxidation pathway that is distinct from the terminal oxidation pathway followed for short-chain n-alkane degradation. Furthermore, our findings suggest that AlmA catalyzes the third reaction in the LC n-alkane degradation pathway.IMPORTANCEMany microbial studies on n-alkane degradation are focused on the genes involved in short-chain n-alkane (≤C16) degradation; however, reports on the genes involved in long-chain (LC) n-alkane (>C20) degradation are limited. Thus far, only AlmA has been reported to be involved in LC n-alkane degradation by Acinetobacter spp.; however, its role in the n-alkane degradation pathway remains elusive. In this study, we conducted a detailed characterization of AlmA in A. baylyi ADP1 and found that AlmA exhibits Baeyer-Villiger monooxygenase activity, thus indicating the presence of a novel LC n-alkane biodegradation mechanism in strain ADP1.

Potential for Use of Species in the Subfamily Erynioideae for Biological Control and Biotechnology.

The fungal order Entomophthorales in the Zoopagomycota includes many fungal pathogens of arthropods. This review explores six genera in the subfamily Erynioideae within the family Entomophthoraceae, namely, Erynia, Furia, Orthomyces, Pandora, Strongwellsea, and Zoophthora. This is the largest subfamily in the Entomophthorales, including 126 described species. The species diversity, global distribution, and host range of this subfamily are summarized. Relatively few taxa are geographically widespread, and few have broad host ranges, which contrasts with many species with single reports from one location and one host species. The insect orders infected by the greatest numbers of species are the Diptera and Hemiptera. Across the subfamily, relatively few species have been cultivated in vitro, and those that have require more specialized media than many other fungi. Given their potential to attack arthropods and their position in the fungal evolutionary tree, we discuss which species might be adopted for biological control purposes or biotechnological innovations. Current challenges in the implementation of these species in biotechnology include the limited ability or difficulty in culturing many in vitro, a correlated paucity of genomic resources, and considerations regarding the host ranges of different species.

The trade-off between individual metabolic specialization and versatility determines the metabolic efficiency of microbial communities.

In microbial systems, a metabolic pathway can be either completed by one autonomous population or distributed among a consortium performing metabolic division of labor (MDOL). MDOL facilitates the system's function by reducing the metabolic burden; however, it may hinder the function by reducing the exchange efficiency of metabolic intermediates among individuals. As a result, the function of a community is influenced by the trade-offs between the metabolic specialization and versatility of individuals. To experimentally test this hypothesis, we deconstructed the naphthalene degradation pathway into four steps and introduced them individually or combinatorically into different strains with varying levels of metabolic specialization. Using these strains, we engineered 1,456 synthetic consortia and found that 74 consortia exhibited higher degradation function than both the autonomous population and rigorous MDOL consortium. Quantitative modeling provides general strategies for identifying the most effective MDOL configuration. Our study provides critical insights into the engineering of high-performance microbial systems.

A high risk of postoperative periprosthetic femoral fracture in Dorr type C femurs: a retrospective cohort study with 10-year follow-up data and a preliminary monochromatic image analysis.

BACKGROUND: The authors applied Anatomique Benoist Girard II (ABG II) stems for total hip arthroplasty in some Dorr type C femurs as early attempts. Here, the authors compared the long-term follow-up results between ABG II stems and the 'well-performing' Corail stems and their monochromatic images. METHODS: Among 3214 primary total hip arthroplasty records, 43 short ABG II stems and 67 standard-length Corail stems implanted in Dorr type C femurs were eligible and enrolled in this retrospective cohort study, with a mean follow-up of 10.3 years. Revision rates, Harris hip scores, and radiologic signs were compared. Spectral CT scans from a representative sample were obtained, and monochromatic images were reconstructed. A quantitative method was developed to measure the volume of the gap around stems. Patient-specific finite element analysis was conducted to investigate the strains. RESULTS: The revision rate of ABG II stems was significantly higher than that of Corail stems (21 vs. 3%, P <0.05). In the monochromatic images, fewer spot-weld signs (2.2 vs. 3.4, P <0.05) and wider gaps around stems (1.64 cm 3 vs. 0.13 cm 3 , P <0.05) were observed on average in the ABG II group. The mean maximum principal strains of the proximal femurs in the ABG II group were close to the yield strains and significantly larger than those in the Corail group (0.0052 vs. 0.0011, P <0.05). CONCLUSIONS: There was a high risk of postoperative periprosthetic femoral fracture for ABG II stems in Dorr type C femurs. Monochromatic images provided some insight into the failure mechanism. LEVEL OF EVIDENCE: III.

Dietary supplementation with Acremonium terricola culture alters the gut microbial structure and improves the growth performance, antioxidant status, and immune function of weaning piglets.

BACKGROUND: Acremonium terricola is used in the feed of dairy animals to promote growth and control diseases. However, the effects of dietary supplementation with A. terricola on the gut microbial structure of weaning piglets remain poorly understood. Therefore, in this study, we investigated the effects of dietary supplementation with A. terricola culture (ATC) on the growth performance, antioxidant status, immunity, and gut environment of weaning piglets. Sixty piglets were fed a basal diet supplemented with 1 g ATC/kg of basal diet (experimental group). Another 60 piglets did not receive ATC (control group). The intervention lasted for 20 days. RESULTS: The experimental group had higher daily weight gain and feed efficiency than did the control group. Significant increases were noted in the levels of serum insulin (P = 0.0018), insulin-like growth factor (P = 0.0018), triiodothyronine (P = 0.0031), immunoglobulin A (P < 0.0001), immunoglobulin M (P = 0.001), immunoglobulin G (P = 0.0001), and interferon γ (P < 0.0001) in the experimental group compared with the levels in the control group. Furthermore, ATC supplementation significantly reduced (P < 0.05) the relative abundance of Shuttleworthia, Succinivibrio, Roseburia, Ruminococcus, and Paludibacter but increased that of Phascolarctobacterium, Megasphaera, Faecalibacterium, and Prevotella in the experimental group compared with that in the control group. Notably, ATC supplementation significantly increased the relative abundance of Faecalibacterium prausnitzii (P < 0.05), which is involved in anti-inflammatory activities, gut barrier enhancement, and butyrate production. CONCLUSIONS: Dietary supplementation with ATC may improve the growth performance, antioxidant status, immunity, and fecal microflora of weaning pigs.

Nonreciprocal Antisymmetric Magnetoresistance and Unconventional Hall Effect in a Two-Dimensional Ferromagnet.

Two-dimensional (2D) ferromagnets with high Curie temperatures provide a rich platform for exploring the exotic phenomena of 2D magnetism and the potential of spintronic devices. As a prototypical 2D ferromagnet, Fe5-xGeTe2 has recently been reported to possess a high Curie temperature with Tc ∼ 310 K, making it a promising candidate for advancing 2D nanoelectromechanical systems. However, due to its intricate magnetic ground state and magnetic domains, a thorough study of the transport behavior related to its lattice and domain structures is still lacking. Here, we report a nonreciprocal antisymmetric magnetoresistance in Fe5-xGeTe2 nanoflakes observed under an external magnetic field between 85-120 K. Through a detailed examination of its temperature, field orientation, and sample thickness dependence, we trace its origin to an additional electric field induced by the domain structure. This differs from the previously reported antisymmetric magnetoresistance due to thickness inhomogeneity. Notably, at lower temperatures, we observed an unconventional Hall effect (UHE), which can be attributed to the Dzyaloshinskii-Moriya interaction (DMI) resulting from the non-coplanar magnetic moment structure. The pronounced influence of sample thickness on magneto-transport properties underscores the competition between magnetic anisotropy and DMI in Fe5-xGeTe2 flakes with varying thicknesses. Our findings provide a deeper understanding of the magneto-transport behavior of the exotic magnetic structure in 2D ferromagnetic materials, which may benefit future spintronic device applications.

Home-based tele-rehabilitation versus hospital-based outpatient rehabilitation for pain and function after initial total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to compare the effectiveness of home-based tele-rehabilitation programs with hospital-based rehabilitation programs in improving pain and function at various time points (≤6 weeks, ≤14 weeks, and ≤ 52 weeks) following the initial total knee arthroplasty. METHODS: This study used PRISMA and AMSTAR reporting guidelines. We systematically searched 5 databases (PubMed, Embase, Web of Science, Cochrane Library, and Medline) to identify randomized controlled trials published from January 1, 2019, to January 1, 2023. The primary outcomes were pain, knee injury and osteoarthritis outcome score, and mobility (knee range of motion). RESULTS: We included 9 studies involving 1944 patients. Low-quality evidence showed hospital-based rehabilitation was better than home-based tele-rehabilitation in knee injury and osteoarthritis outcome score (mean difference [MD], -2.62; 95% confidence interval [CI], -4.65 to -0.58; P = .01) at ≤ 14 weeks after total knee arthroplasty. Based on low-quality evidence, home-based tele-rehabilitation was better than hospital-based rehabilitation in knee range of motion (MD, 2.00; 95% CI, 0.60 to 3.40; P = .005). There was no significant difference between hospital-based rehabilitation and home-based tele-rehabilitation in knee pain at ≤ 6 weeks (MD, 0.18; 95% CI, -0.07 to 0.42; P = .16), 14 weeks (MD, 0.12; 95% CI, -0.26 to 0.49; P = .54), and ≤ 52 weeks (MD, 0.16; 95% CI, -0.11 to 0.43; P = .24). CONCLUSION: Home-based tele-rehabilitation and hospital-based rehabilitation programs showed comparable long-term outcomes in pain, mobility, physical function, and patient-reported health status after primary total knee arthroplasty. Considering the economic costs, home-based tele-rehabilitation programs are recommended as a viable alternative to hospital-based rehabilitation programs.

Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology.

Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.

Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study.

OBJECTIVES: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS: This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).

Roles of sulfate-reducing bacteria in sustaining the diversity and stability of marine bacterial community.

Microbes play central roles in ocean food webs and global biogeochemical processes. Yet, the information available regarding the highly diverse bacterial communities in these systems is not comprehensive. Here we investigated the diversity, assembly process, and species coexistence frequency of bacterial communities in seawater and sediment across ∼600 km of the eastern Chinese marginal seas using 16S rRNA gene amplicon sequencing. Our analyses showed that compared with seawater, bacterial communities in sediment possessed higher diversity and experienced tight phylogenetic distribution. Neutral model analysis showed that the relative contribution of stochastic processes to the assembly process of bacterial communities in sediment was lower than that in seawater. Functional prediction results showed that sulfate-reducing bacteria (SRB) were enriched in the core bacterial sub-communities. The bacterial diversities of both sediment and seawater were positively associated with the relative abundance of SRB. Co-occurrence analysis showed that bacteria in seawater exhibited a more complex interaction network and closer co-occurrence relationships than those in sediment. The SRB of seawater were centrally located in the network and played an essential role in sustaining the complex network. In addition, further analysis indicated that the SRB of seawater helped maintain the high stability of the bacterial network. Overall, this study provided further comprehensive information regarding the characteristics of bacterial communities in the ocean, and provides new insights into keystone taxa and their roles in sustaining microbial diversity and stability in ocean.