The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice.

This study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides, Blautia, Akkermansia, and Faecalibaculum, and significantly decreased the abundance of Proteus. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote ß-oxidation by increasing the levels of SCFAs. Faecalibaculum, Blautia, Bacteroides, and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum, Blautia, Bacteroides, and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.

Perivascular Spaces, Diffusivity Along Perivascular Spaces, and Free Water in Cerebral Small Vessel Disease.

BACKGROUND AND OBJECTIVES: Previous studies have linked the MRI measures of perivascular spaces (PVSs), diffusivity along the perivascular spaces (DTI-ALPS), and free water (FW) to cerebral small vessel disease (SVD) and SVD-related cognitive impairments. However, studies on the longitudinal associations between the three MRI measures, SVD progression, and cognitive decline are lacking. This study aimed to explore how PVS, DTI-ALPS, and FW contribute to SVD progression and cognitive decline. METHODS: This is a cohort study that included participants with SVD who underwent neuroimaging and cognitive assessment, specifically measuring Mini-Mental State Examination (MMSE), cognitive index, and processing speed, at 2 time points. Three MRI measures were quantified: PVS in basal ganglia (BG-PVS) volumes, FW fraction, and DTI-ALPS. We performed a latent change score model to test inter-relations between the 3 MRI measures and linear regression mixed models to test their longitudinal associations with the changes of other SVD MRI markers and cognitive performances. RESULTS: In baseline assessment, we included 289 participants with SVD, characterized by a median age of 67.0 years and 42.9% women. Of which, 220 participants underwent the follow-up assessment, with a median follow-up time of 3.4 years. Baseline DTI-ALPS was associated with changes in BG-PVS volumes (ß = -0.09, p = 0.030), but not vice versa (ß = -0.08, p = 0.110). Baseline BG-PVS volumes were associated with changes in white matter hyperintensity (WMH) volumes (ß = 0.33, p-corrected < 0.001) and lacune numbers (ß = 0.28, p-corrected < 0.001); FW fraction was associated with changes in WMH volumes (ß = 0.30, p-corrected < 0.001), lacune numbers (ß = 0.28, p-corrected < 0.001), and brain volumes (ß = -0.45, p-corrected < 0.001); DTI-ALPS was associated with changes in WMH volumes (ß = -0.20, p-corrected = 0.002) and brain volumes (ß = 0.23, p-corrected < 0.001). Furthermore, baseline FW fraction was associated with decline in MMSE score (ß = -0.17, p-corrected = 0.006); baseline FW fraction and DTI-ALPS were associated with changes in cognitive index (FW fraction: ß = -0.25, p-corrected < 0.001; DTI-ALPS: ß = 0.20, p-corrected = 0.001) and processing speed over time (FW fraction: ß = -0.29, p-corrected < 0.001; DTI-ALPS: ß = 0.21, p-corrected < 0.001). DISCUSSION: Our results showed that increased BG-PVS volumes, increased FW fraction, and decreased DTI-ALPS are related to progression of MRI markers of SVD, along with SVD-related cognitive decline over time. These findings may suggest that the glymphatic dysfunction is related to SVD progression, but further studies are needed.

Development of adenoviral vectors that transduce Purkinje cells and other cerebellar cell-types in the cerebellum of a humanized mouse model.

Viral vector gene therapy has immense promise for treating central nervous system (CNS) disorders. Although adeno-associated virus vectors (AAVs) have had success, their small packaging capacity limits their utility to treat the root cause of many CNS disorders. Adenoviral vectors (Ad) have tremendous potential for CNS gene therapy approaches. Currently, the most common vectors utilize the Group C Ad5 serotype capsid proteins, which rely on the Coxsackievirus-Adenovirus receptor (CAR) to infect cells. However, these Ad5 vectors are unable to transduce many neuronal cell types that are dysfunctional in many CNS disorders. The human CD46 (hCD46) receptor is widely expressed throughout the human CNS and is the primary attachment receptor for many Ad serotypes. Therefore, to overcome the current limitations of Ad vectors to treat CNS disorders, we created chimeric first generation Ad vectors that utilize the hCD46 receptor. Using a "humanized" hCD46 mouse model, we demonstrate these Ad vectors transduce cerebellar cell types, including Purkinje cells, that are refractory to Ad5 transduction. Since Ad vector transduction properties are dependent on their capsid proteins, these chimeric first generation Ad vectors open new avenues for high-capacity helper-dependent adenovirus (HdAd) gene therapy approaches for cerebellar disorders and multiple neurological disorders.

Dose-effect of exercise intervention on heart rate variability of acclimatized young male lowlanders at 3,680 m.

This study investigated whether exercise could improve the reduced HRV in an environment of high altitude. A total of 97 young, healthy male lowlanders living at 3,680 m for >1 year were recruited. They were randomized into four groups, of which three performed-low-, moderate-, and high-intensity (LI, MI, HI) aerobic exercise for 4 weeks, respectively. The remaining was the control group (CG) receiving no intervention. For HI, compared to other groups, heart rate (p = 0.002) was significantly decreased, while standard deviation of RR intervals (p < 0.001), SD2 of Poincaré plot (p = 0.046) and the number of successive RR interval pairs that differ by > 50 ms divided by total number of RR (p = 0.032), were significantly increased after intervention. For MI, significantly increase of trigonometric interpolation in NN interval (p = 0.016) was observed after exercise. Further, a decrease in systolic blood pressure (SBP) after high-intensity exercise was found significantly associated with an increase in SD2 (r = - 0.428, p = 0.042). These results indicated that there was a dose effect of different intensities of aerobic exercise on the HRV of acclimatized lowlanders. Moderate and high-intensity aerobic exercise would change the status of the autonomic nervous system (ANS) and decrease the blood pressure of acclimatized lowlanders exposed to high altitude.

Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling.

Auditory sensitivity and frequency resolution depend on the optimal transfer of sound-induced vibrations from the basilar membrane (BM) to the inner hair cells (IHCs), the principal auditory receptors. There remains a paucity of information on how this is accomplished along the frequency range in the human cochlea. Most of the current knowledge is derived either from animal experiments or human tissue processed after death, offering limited structural preservation and optical resolution. In our study, we analyzed the cytoarchitecture of the human cochlear partition at different frequency locations using high-resolution microscopy of uniquely preserved normal human tissue. The results may have clinical implications and increase our understanding of how frequency-dependent acoustic vibrations are carried to human IHCs. A 1-micron-thick plastic-embedded section (mid-modiolar) from a normal human cochlea uniquely preserved at lateral skull base surgery was analyzed using light and transmission electron microscopy (LM, TEM). Frequency locations were estimated using synchrotron radiation phase-contrast imaging (SR-PCI). Archival human tissue prepared for scanning electron microscopy (SEM) and super-resolution structured illumination microscopy (SR-SIM) were also used and compared in this study. Microscopy demonstrated great variations in the dimension and architecture of the human cochlear partition along the frequency range. Pillar cell geometry was closely regulated and depended on the reticular lamina slope and tympanic lip angle. A type II collagen-expressing lamina extended medially from the tympanic lip under the inner sulcus, here named "accessory basilar membrane." It was linked to the tympanic lip and inner pillar foot, and it may contribute to the overall compliance of the cochlear partition. Based on the findings, we speculate on the remarkable microanatomic inflections and geometric relationships which relay different sound-induced vibrations to the IHCs, including their relevance for the evolution of human speech reception and electric stimulation with auditory implants. The inner pillar transcellular microtubule/actin system's role of directly converting vibration energy to the IHC cuticular plate and ciliary bundle is highlighted.

Domain generalization for retinal vessel segmentation via Hessian-based vector field.

Blessed by vast amounts of data, learning-based methods have achieved remarkable performance in countless tasks in computer vision and medical image analysis. Although these deep models can simulate highly nonlinear mapping functions, they are not robust with regard to the domain shift of input data. This is a significant concern that impedes the large-scale deployment of deep models in medical images since they have inherent variation in data distribution due to the lack of imaging standardization. Therefore, researchers have explored many domain generalization (DG) methods to alleviate this problem. In this work, we introduce a Hessian-based vector field that can effectively model the tubular shape of vessels, which is an invariant feature for data across various distributions. The vector field serves as a good embedding feature to take advantage of the self-attention mechanism in a vision transformer. We design paralleled transformer blocks that stress the local features with different scales. Furthermore, we present a novel data augmentation method that introduces perturbations in image style while the vessel structure remains unchanged. In experiments conducted on public datasets of different modalities, we show that our model achieves superior generalizability compared with the existing algorithms. Our code and trained model are publicly available at https://github.com/MedICL-VU/Vector-Field-Transformer.

A comparison of endovascular therapy and medical management in patients with large vessel occlusion mild stroke treated between 2015 and 2023: a systematic review and meta-analysis.

OBJECTIVE: Endovascular therapy (EVT) is recommended for patients with acute large-vessel occlusion (LVO) However, its efficacy and safety compared to medical management (MM) in patients with a National Institutes of Health Stroke Scale (NIHSS) score of ≤6 remains unclear. This meta-analysis compared EVT with medical MM in patients with large vessel occlusion mild stroke treated between 2015 and 2023, following the publication of the first randomized controlled trial. MATERIALS AND METHODS: Biomedical database searches (inception to March 21, 2023) retrieved articles reporting favorable functional outcome(modified Rankin Scale [mRS] 0-1) and functional independence (mRS 0-2), 90-day mortality and symptomatic intracranial hemorrhage (sICH). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) to maintain methodological rigor and transparency in our meta-analysis. RESULTS: We conducted a meta-analysis of 22 studies (4,985 patients) to reveal no significant differences in favorable functional outcomes and independence across all groups. However, in patients treated between 2015 and 2023, EVT exhibited a higher risk of 90-day mortality (Odds Ratio [OR] = 1.84, 95% Confidence Interval [CI] [1.10, 3.07], p = 0.02) and sICH (OR = 3.36, 95% CI [1.96, 6.66], p < 0.01). EVT correlated with elevated sICH in the anterior circulation (OR=2.94, 95%CI [1.82, 4.74], p<0.01) regardless of the proximal (OR=2.20, 95%CI [1.04, 4.69], p=0.04) or distal (OR=3.44, 95%CI [1.43, 8.32], p<0.01) location of the occlusion. EVT correlated with elevated sICH rates in patients treated within 6 hours of symptom onset or those with NHISS≤5. CONCLUSION: In patients treated between 2015 and 2023, EVT and MM did not differ in efficacy in acute LVO mild stroke; MM associated with better safety outcomes. Rigorous randomized controlled trials are warranted.

Amorphous Cobalt Polyselenides with Hyperbranched Polymer Additive as High-Capacity Magnesium Storage Cathode Materials Through Cationic and Anionic Co-Redox Mechanism.

Rechargeable magnesium batteries (RMBs) are a promising energy-storage technology with low cost and high reliability, while the lack of high-performance cathodes is impeding the development. Herein, a series of amorphous cobalt polyselenides (CoSex, x>2) is synthesized with the assistance of organic amino-terminal hyperbranched polymer (AHP) additive and investigated as cathodes for RMBs. The coordination of cobalt cations with the amino groups of AHP leads to the formation of amorphous CoSex rather than crystalline CoSe2. The amorphous structure is favorable for magnesium-storage reaction kinetics, and the polyselenide anions provide extra capacities besides the redox of cobalt cations. Moreover, the organic AHP molecules retained in CoSex-AHP provide an elastic matrix to accommodate the volume change of conversion reaction. With a moderate x value (2.73) and appropriate AHP content (11.58%), CoSe2.7-AHP achieves a balance between capacity and cycling stability. Amorphous CoSe2.7-AHP provides high capacities of 246.6 and 94 mAh g‒1, respectively, at 50 and 2000 A g‒1, as well as a capacity retention rate of 68.5% after 300 cycles. The mechanism study demonstrates CoSex-AHP undergoes reversible redox of Co2+/3+↔Co0 and Sen 2‒↔Se2‒. The present study demonstrates amorphous polyselenides with cationic-anionic redox activities is as a feasible strategy to construct high-capacity cathode materials for RMBs.

Effect of Different Drying Methods on the Quality of Oudemansiella raphanipes.

In this study, we used fresh Oudemansiella raphanipes as raw materials and pre-treated through hot air drying (HD), infrared radiation drying (ID), and vacuum freeze drying (VD) to investigate the effects of different drying methods on the rehydration rate, appearance quality, microstructure, and volatile flavor components of the dried products, as well as to determine the physicochemical properties and bioactivities of the polysaccharides in the dried O. raphanipes. The results showed that the VD O. raphanipes had the highest rehydration rate and the least shrinkage in appearance, and it better maintained the original color of the gills, but their aroma was not as strong as that of the HD samples. The scanning electron microscopy results indicate that VD maintains a good porous structure in the tissue, while HD and ID exhibit varying degrees of shrinkage and collapse. Seventy-five common volatile substances were detected in the three dried samples, mainly alkanes, alcohols, and esters. The polysaccharides (PS-H, PS-I, and PS-V) extracted from the dried samples of these three species of O. raphanipes had similar infrared spectral features, indicating that their structures are basically consistent. The highest yield was obtained for PS-V, and the polysaccharide content and glucuronic acid content of PS-I were higher than those of the remaining two polysaccharides. In addition, PS-V also showed better antioxidant activity and inhibitory activity against α-glucosidase as well as α-amylase. In conclusion, among the above three drying methods, the quality of O. raphanipes obtained by vacuum freeze drying is the best, and this experiment provides a theoretical basis for the selection of drying methods for O. raphanipes.

Circulating immune cell landscape and T-cell abnormalities in patients with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. METHODS: In this study, we employed a combination of single-cell RNA sequencing (scRNA-seq), mass cytometry and RNA-sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age-matched healthy controls. RESULTS: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T-cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA-DR and p-STAT3. CONCLUSIONS: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T-cell populations, including a decrease in effector T-cells and an increase in regulatory T-cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.

High-Loading Smart Carrier Containing 2-Mercaptobenzimidazole-Zn2+-Polydopamine with pH-Responsive Function to Fabricate High-Performance Waterborne Epoxy Anticorrosion Coatings.

Corrosion inhibitor additives are considered to be one of the effective methods to slow down the corrosion of metals, but the corrosion inhibitors will decompose and lose their effect in a long-term corrosive environment. In this work, a smart corrosion inhibitor carrier 2-mercaptobenzimidazole-Zn2+-polydopamine@graphite (MZPG) with excellent pH response was designed and synthesized using a one-pot method. This corrosion inhibitor carrier not only has a very high 2-mercaptobenzimidazole (MBI) loading capacity (38.0%) but also maintains a very low MBI activity to inhibit the decomposition of MZPG in the environment as much as possible. The MZPG/epoxy (MZPG/EP) coatings prepared by the spraying method showed excellent mechanical properties. Electrochemical and salt spray tests showed that the MZPG/EP coatings (1.20 × 1010 Ω·cm2) have excellent corrosion resistance with Rp values up to 3 orders of magnitude higher than that of the EP coating (1.25 × 107 Ω·cm2). Notably, the MZPG/EP coatings maintained good corrosion resistance under acidic conditions due to the pH-responsive release of corrosion inhibitors. This is of great significance for the future development of coatings for highly corrosive environments.

A novel deep generative model for mRNA vaccine development: Designing 5' UTRs with N1-methyl-pseudouridine modification.

Efficient translation mediated by the 5' untranslated region (5' UTR) is essential for the robust efficacy of mRNA vaccines. However, the N1-methyl-pseudouridine (m1Ψ) modification of mRNA can impact the translation efficiency of the 5' UTR. We discovered that the optimal 5' UTR for m1Ψ-modified mRNA (m1Ψ-5' UTR) differs significantly from its unmodified counterpart, highlighting the need for a specialized tool for designing m1Ψ-5' UTRs rather than directly utilizing high-expression endogenous gene 5' UTRs. In response, we developed a novel machine learning-based tool, Smart5UTR, which employs a deep generative model to identify superior m1Ψ-5' UTRs in silico. The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models. As a result, Smart5UTR can successfully design superior 5' UTRs, greatly benefiting mRNA vaccine development. Notably, Smart5UTR-designed superior 5' UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2, surpassing the performance of vaccines using high-expression endogenous gene 5' UTRs.

SpectralGPT: Spectral Remote Sensing Foundation Model.

The foundation model has recently garnered significant attention due to its potential to revolutionize the field of visual representation learning in a self-supervised manner. While most foundation models are tailored to effectively process RGB images for various visual tasks, there is a noticeable gap in research focused on spectral data, which offers valuable information for scene understanding, especially in remote sensing (RS) applications. To fill this gap, we created for the first time a universal RS foundation model, named SpectralGPT, which is purpose-built to handle spectral RS images using a novel 3D generative pretrained transformer (GPT). Compared to existing foundation models, SpectralGPT 1) accommodates input images with varying sizes, resolutions, time series, and regions in a progressive training fashion, enabling full utilization of extensive RS Big Data; 2) leverages 3D token generation for spatial-spectral coupling; 3) captures spectrally sequential patterns via multi-target reconstruction; 4) trains on one million spectral RS images, yielding models with over 600 million parameters. Our evaluation highlights significant performance improvements with pretrained SpectralGPT models, signifying substantial potential in advancing spectral RS Big Data applications within the field of geoscience across four downstream tasks: single/multi-label scene classification, semantic segmentation, and change detection.

Synthesis of sinomenine derivatives with potential anti-leukemia activity.

In recent years, with sinomenine hydrochloride as the main ingredient, Qingfengteng had been formulated as various dosage forms for clinical treatment. Subsequent findings confirmed a variety of biological roles for sinomenine. Here, 15 H2S-donating sinomenine derivatives were synthesized. Target hybrids a11 displayed substantial cytotoxic effects on cancer cell lines, particularly against K562 cells, with an IC50 value of 1.36 µM. In-depth studies demonstrated that a11 arrested cell cycle at G1 phase, induced apoptosis via both morphological changes in nucleus and membrane potential collapse in mitochondria. These results indicated a11 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.

Introduction: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS. Aim: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS. Methods: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT. Results: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased. Conclusion: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.

Nanozymes with biomimetically designed properties for cancer treatment.

Nanozymes, as a type of nanomaterials with enzymatic catalytic activity, have demonstrated tremendous potential in cancer treatment owing to their unique biomedical properties. However, the heterogeneity of tumors and the complex tumor microenvironment pose significant challenges to the in vivo catalytic efficacy of traditional nanozymes. Drawing inspiration from natural enzymes, scientists are now using biomimetic design to build nanozymes from the ground up. This approach aims to replicate the key characteristics of natural enzymes, including active structures, catalytic processes, and the ability to adapt to the tumor environment. This achieves selective optimization of nanozyme catalytic performance and therapeutic effects. This review takes a deep dive into the use of these biomimetically designed nanozymes in cancer treatment. It explores a range of biomimetic design strategies, from structural and process mimicry to advanced functional biomimicry. A significant focus is on tweaking the nanozyme structures to boost their catalytic performance, integrating them into complex enzyme networks similar to those in biological systems, and adjusting functions like altering tumor metabolism, reshaping the tumor environment, and enhancing drug delivery. The review also covers the applications of specially designed nanozymes in pan-cancer treatment, from catalytic therapy to improved traditional methods like chemotherapy, radiotherapy, and sonodynamic therapy, specifically analyzing the anti-tumor mechanisms of different therapeutic combination systems. Through rational design, these biomimetically designed nanozymes not only deepen the understanding of the regulatory mechanisms of nanozyme structure and performance but also adapt profoundly to tumor physiology, optimizing therapeutic effects and paving new pathways for innovative cancer treatment.

A deep learning-based approach for fully automated segmentation and quantitative analysis of muscle fibers in pig skeletal muscle.

Muscle fiber properties exert a significant influence on pork quality, with cross-sectional area (CSA) being a crucial parameter closely associated with various meat quality indicators, such as shear force. Effectively identifying and segmenting muscle fibers in a robust manner constitutes a vital initial step in determining CSA. This step is highly intricate and time-consuming, necessitating an accurate and automated analytical approach. One limitation of existing methods is their tendency to perform well on high signal-to-noise ratio images of intact, healthy muscle fibers but their lack of validation on more complex image datasets featuring significant morphological changes, such as the presence of ice crystals. In this study, we undertake the fully automatic segmentation of muscle fiber microscopic images stained with myosin adenosine triphosphate (mATPase) activity using a deep learning architecture known as SOLOv2. Our objective is to efficiently derive accurate measurements of muscle fiber size and distribution. Tests conducted on actual images demonstrate that our method adeptly handles the intricate task of muscle fiber segmentation, yielding quantitative results amenable to statistical analysis and displaying reliability comparable to manual analysis.

Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1ß⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn's disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn's disease.

Association of cardiovascular disease prevalence with BMD and fracture in men with T2DM.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.

Wickerhamomyces corioli f.a., sp. nov., a novel yeast species discovered in two mushroom species.

Two yeast strains, designated as 19-39-3 and 19-40-2, obtained from the fruiting bodies of Trametes versicolor and Marasmius siccus collected in Yunwu Mountain Forest Park, PR China, have been identified as representing a novel asexual ascomycetous yeast species. From the results of phylogenetic analyses of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA, small subunit (SSU) rRNA and translation elongation factor 1-α (TEF1) genes, it was determined that these strains represent a member of the genus Wickerhamomyces, with Wickerhamomyces alni and Candida ulmi as the closest relatives. The novel species exhibited 6.6 and 6.7% differences in the D1/D2 domains compared with W. alni and C. ulmi, respectively. Additionally, distinct biochemical and physiological differences were observed between the novel species and its related counterparts. No sexual reproduction was observed in these strains, leading to the proposal of the name Wickerhamomyces corioli f.a., sp. nov. for this newly discovered species.