Melatonin-loaded bioactive microspheres accelerate aged bone regeneration by formation of tunneling nanotubes to enhance mitochondrial transfer.

The repair of bone defects in the elderly individuals is significantly delayed due to cellular senescence and dysfunction, which presents a challenge in clinical settings. Furthermore, there are limited effective methods available to promote bone repair in older individuals. Herein, melatonin-loaded mesoporous bioactive glasses microspheres (MTBG) were successfully prepared based on their mesoporous properties. The repair of bone defects in aged rats was significantly accelerated by enhancing mitochondrial function through the sustained release of melatonin and bioactive ions. MTBG effectively rejuvenated senescent bone marrow mesenchymal stem cells (BMSCs) by scavenging excessive reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential (ΔΨm), and increasing ATP synthesis. Analysis of the underlying mechanism revealed that the formation of tunneling nanotubes (TNTs) facilitated the intercellular transfer of mitochondria, thereby resulting in the recovery of mitochondrial function. This study provides critical insights into the design of new biomaterials for the elderly individuals and the biological mechanism involved in aged bone regeneration.

The global burden and trend of Clostridioides difficile and its association with world antibiotic consumption, 1990-2019.

Background: To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption. Methods: Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated to explore the relationship between CDI and antibiotics. Results: Globally, CDI is the most significant one with a high-rocketing burden increase rate among 13 pathogens causing diarrheal deaths and disability-adjusted life years (DALYs). The age-standardised death rate (ASDR) increased from 0.19 in 1990 to 0.43 in 2019, in which the elderly and females are at higher risk. A rapid increase in ASDR in high to middle sociodemographic index (SDI) regions such as North America (average annual percentage change (AAPC) = 7.71%), Andean (AAPC = 7.82%), and Southern Latin America (AAPC = 11.08%) was identified. Antibiotic consumption has a significant positive correlation with CDI with different risk stratifications. Conclusions: The global burden of CDI has continuously increased for the past 30 years, especially in high to middle-SDI regions. World antibiotic consumption showed a strong positive correlation with CDI with different risk stratification. More effective prevention and control measures should be implemented in these critical regions, with a specific emphasis on vulnerable populations, to mitigate the spread of epidemics.

Impact of COVID-19 pandemic on adolescents undergoing metabolic bariatric surgery.

BACKGROUND: While the lasting effect of the COVID-19 pandemic continues to unfold, the impact on adolescents undergoing bariatric surgery remains unseen. OBJECTIVE: We examined the impact of the pandemic on adolescents undergoing metabolic bariatric surgery. SETTING: Academic hospital, New York, NY. METHODS: A single-institution review of prospectively collected data evaluated adolescents who underwent laparoscopic sleeve gastrectomy between 2010 and 2023, forming two cohorts: pre-COVID (before March 1, 2019) and COVID (after March 1, 2020). Absolute and percent weight loss and body mass index (BMI) change at 6 and 12 months postsurgery were compared between cohorts. Multivariable linear regression models were constructed to estimate the association between weight loss, adjusting for age, gender, ethnicity, and BMI. RESULTS: A total of 358 patients were included: 245 in the pre-COVID cohort and 113 in the COVID cohort. There were no significant differences in baseline characteristics. There were no significant differences between cohorts at 6 months in weight loss (21.6 kg vs. 22.5 kg, P = .43), percent weight loss (18% vs. 18%, P = .63), and BMI change (8.0 vs. 8.4, P = .39) which was maintained at 12 months. In multivariate models, after adjusting for age, gender, ethnicity, and baseline BMI, undergoing surgery during the pandemic was not associated with a difference in weight loss or BMI change at 6 and 12 months postoperatively. CONCLUSION: Despite the severe societal impact of the COVID-19 pandemic, laparoscopic sleeve gastrectomy remained a durable intervention for adolescent obesity, with no observed differences in weight loss in patients undergoing surgery during the pandemic compared to prepandemic.

Efficient Fabrication of Disordered Graphene with Improved Ion Accessibility, Ion Conductivity, and Density for High-Performance Compact Capacitive Energy Storage.

High-performance compact capacitive energy storage is vital for many modern application fields, including grid power buffers, electric vehicles, and portable electronics. However, achieving exceptional volumetric performance in supercapacitors is still challenging and requires effective fabrication of electrode films with high ion-accessible surface area and fast ion diffusion capability while simultaneously maintaining high density. Herein, a facile, efficient, and scalable method is developed for the fabrication of dense, porous, and disordered graphene through spark-induced disorderly opening of graphene stacks combined with mechanical compression. The obtained disordered graphene achieves a high density of 1.18 g cm-3, sixfold enhanced ion conductivity compared to common laminar graphene, and an ultrahigh volumetric capacitance of 297 F cm-3 in ionic liquid electrolyte. The fabricated stack cells deliver a volumetric energy density of 94.2 Wh L-1 and a power density of 13.7 kW L-1, representing a critical breakthrough in capacitive energy storage. Moreover, the proposed disordered graphene electrodes are assembled into ionogel-based all-solid-state pouch cells with high mechanical stability and multiple optional outputs, demonstrating great potential for flexible energy storage in practical applications.

Prevalence and genotypes of Chlamydia psittaci in birds and related workers in three cities of China.

Chlamydia psittaci-a zoonotic pathogen in birds-may be transmitted to humans, causing severe respiratory disease. Individuals working in or living near poultry farms are highly susceptible to C. psittaci infection. In this study, we assessed the prevalence and genotypes of C. psittaci in poultries and humans in three cities of China by collecting fecal samples from different poultry species and throat swab samples and serum samples from workers in poultry farms and zoos. These samples were screened by real-time fluorescence quantitative PCR (qPCR) targeting C. psittaci ompA. The positive samples were subjected to PCR amplification and sequencing of ompA. The strains detected in the samples were genotyped on the basis of the phylogenetic analysis of ompA sequences. In total, 3.13% (40/1278) poultry fecal samples were positive in the qPCR assay, whereas 3.82% (6/157) of throat swab samples and 42.59% (46/108) of serum samples from the workers were positive in the qPCR and indirect fluorescent antibody assays, respectively. The strains detected in the 32 poultry samples and 6 human samples were genotyped as type A, indicating that the workers were infected with C. psittaci that originated in poultry birds in farms. Additionally, eight peacocks showed strains with the genotype CPX0308, which was identified in China for the first time. Elucidating the distribution of C. psittaci in animals and poultry-related workers may provide valuable insights for reducing the risk of C. psittaci infection within a population.

ZnMn2(PO4)2·nH2O: An H2O-Imbedding-Activated Cathode for Robust Aqueous Zinc-Ion Batteries.

Component modulation endows Mn-based electrodes with prominent energy storage properties due to their adjustable crystal structure characteristics. Herein, ZnMn2(PO4)2·nH2O (ZMP·nH2O) was obtained by a hydration reaction from ZnMn2(PO4)2 (ZMP) during an electrode-aging evolution. Benefiting from the introduction of lattice H2O molecules into the ZMP structure, the ion transmission path has been expanded along with the extended d-spacing, which will further facilitate the ZMP → ZMP·nH2O phase evolution and electrochemical reaction kinetics. Meanwhile, the hydrogen bond can be generated between H2O and O in PO43-, which strengthens the structure stability of ZMP·nH2O and lowers the conversion barrier from ZMP to ZMP·4H2O during the Zn2+ uptake/removal process. Thereof, ZMP·nH2O delivers enhanced electrochemical reaction kinetics with robust structure tolerance (106.52 mA h g-1 at 100 mA g-1 over 620 cycles). This high-energy aqueous Zn||ZMP·nH2O battery provides a facile strategy for engineering and exploration of high-performance ZIBs to realize the practical application of Mn-based cathodes.

Vitamin D/vitamin D receptor protects intestinal barrier against colitis by positively regulating Notch pathway.

Objective: Vitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection. Methods: Genetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids. Results: VD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription. Conclusion: VD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.

Global microplastic fiber pollution from domestic laundry.

The rapid expansion of fast fashion has significantly increased microplastic fiber (MPF) release during laundry practices, accounting for approximately one-third of primary microplastics entering the ocean. Currently, a significant gap exists in global-scale research on the release of MPFs from washing textiles. This study introduces an innovative empirical model to assess the spatial distribution of MPF emissions. The model estimates an annual global emission of 5.69 million tons of MPFs from laundry. Of this total, machine washing accounts for the majority (93.7 %), with hand washing contributing the remaining 6.3 %. As the primary source of MPF pollution, Asia's emissions reach 3.71 million tons, far exceeding those of North America (1.18 million tons) and Europe (0.45 million tons). The primary issue is that wastewater management efficiency varies significantly worldwide. In Asia, there is persistently high discharge of MPFs into natural waters, and the removal efficiency of wastewater treatment plants is still comparatively low. In contrast, the United States and many European countries exhibit better MPF retention. The global nature of this challenge mandates international collaboration for comprehensive environmental conservation. Our study provides the first high-resolution global distribution map of MPF emissions and discharge into natural waters, establishing a data foundation for global and regional management of microplastics originating from household laundry sources.

Three Birds with One Stone: Copper Ions Assisted Synergistic Cuproptosis/Chemodynamic/Photothermal Therapy by a Three-Pronged Approach.

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

Enhanced Thermoelectric Performance of N-Type PbSe Through Semi-Coherent Nanostructure by AgCuTe Alloying.

N-type PbSe thermoelectric materials encounter challenges in improving the power factor due to the single-band structure near the Fermi level, which obstructs typical band convergence. The primary strategy for enhancing the thermoelectric figure of merit (ZT) for n-type PbSe involves reducing lattice thermal conductivity (κlat) by introducing various defect structures. However, lattice mismatches resulting from internal defects within the matrix can diminish carrier mobility, thereby affecting electrical transport properties. In this study, n-type AgCuTe-alloyed PbSe systems achieve a peak ZT value of ≈1.5 at 773 K. Transmission electron microscopy reveals nanoprecipitates of Ag2Te, the room temperature second phase of AgCuTe, within the PbSe matrix. Meanwhile, a unique semi-coherent phase boundary is observed between the PbSe matrix and the Ag2Te nanoprecipitates. This semi-coherent phase interface effectively scatters low-frequency phonons while minimizing damage to carrier mobility. Additionally, the dynamic doping effect of Cu atoms from the decomposition of AgCuTe within the matrix further optimize the high-temperature thermoelectric performance. Overall, these factors significantly enhance the ZT across the whole temperature range. The ZT value of ≈1.5 indicates high competitiveness compared to the latest reported n-type PbSe materials, suggesting that these findings hold promise for advancing the development of efficient thermoelectric systems.

Source localization comparison and combination of OPM-MEG and fMRI to detect sensorimotor cortex responses.

BACKGROUND AND OBJECTIVES: The exploration of various neuroimaging techniques have become focal points within the field of neuroscience research. Magnetoencephalography based on optically pumped magnetometers (OPM-MEG) has shown significant potential to be the next generation of functional neuroimaging with the advantages of high signal intensity and flexible sensor arrangement. In this study, we constructed a 31-channel OPM-MEG system and performed a preliminary comparison of the temporal and spatial relationship between magnetic responses measured by OPM-MEG and blood-oxygen-level-dependent signals detected by functional magnetic resonance imaging (fMRI) during a grasping task. METHODS: For OPM-MEG, the ß-band (15-30 Hz) oscillatory activities can be reliably detected across multiple subjects and multiple session runs. To effectively localize the inhibitory oscillatory activities, a source power-spectrum ratio-based imaging method was proposed. This approach was compared with conventional source imaging methods, such as minimum norm-type and beamformer methods, and was applied in OPM-MEG source analysis. Subsequently, the spatial and temporal responses at the source-level between OPM-MEG and fMRI were analyzed. RESULTS: The effectiveness of the proposed method was confirmed through simulations compared to benchmark methods. Our demonstration revealed an average spatial separation of 10.57 ± 4.41 mm between the localization results of OPM-MEG and fMRI across four subjects. Furthermore, the fMRI-constrained OPM-MEG localization results indicated a more focused imaging extent. CONCLUSIONS: Taken together, the performance exhibited by OPM-MEG positions it as a potential instrument for functional surgery assessment.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-ß-catenin signalling pathway in serous ovarian cancer.

BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

Adverse Technical Events During Aortic Root Replacement.

BACKGROUND: Although adverse technical events during aortic root replacement (ARR) are not uncommon and are extremely challenging, there is scant literature to help surgeons prepare for such situations. We describe our experience of outstanding technical events during ARR. METHODS: This is a retrospective study of 830 consecutive ARRs at a single center from 2012 to 2022. Technical events were defined as intraoperative events that led to an unplanned cardiac procedure, need for mechanical circulatory support, or additional aortic cross-clamping. Logistic regression identified factors associated with operative mortality and technical events. RESULTS: Technical events occurred in 90 patients (10.8%) and were attributed to bleeding (n = 26), nonischemic ventricular dysfunction (n = 23), residual valve disease (n = 20), myocardial ischemia (n = 19), and iatrogenic dissection (n = 2). Prior sternotomy (odds ratio [OR], 2.38; 95% CI, 1.36-4.19; P = .002) and complex aortic valve disease (OR, 3.09; 95% CI, 1.09-8.75; P = .03) were associated with technical events. Patients with technical events had higher rates of operative mortality (6.7% vs 2.3%, P = .03) and all major postoperative complications. Surgical indications of dissection (OR, 13.57; 95% CI, 4.95-37.23; P < .001) and complex aortic valve disease (OR, 14.09; 95% CI, 3.67-54.02; P < .001) but not adverse technical events (OR, 2.42; 95% CI, 0.81-7.26; P = .11) were associated with operative mortality. CONCLUSIONS: Adverse technical events occurred in 10.8% of ARRs and were associated with reoperative sternotomies. Technical events are associated with increased postoperative complications.

Impact of diurnal temperature variations on sputum bacterial detection in hospitalized patients with acute COPD exacerbation: a retrospective study from Fuzhou, China.

OBJECTIVE: To investigate the association between meteorological data three days before admission and the status of sputum pathogens culture in hospitalized patients with Acute exacerbation of Chronic obstructive pulmonary disease (AECOPD) and respiratory infections. METHODS: Data from 1,370 AECOPD patients (80.66% males, approximately 80% age > 70) with respiratory infections hospitalized in Fujian Provincial Hospital between December 2013 and December 2019 were collected. This cohort comprised, along with concurrent meteorological data from Fuzhou. Group differences were analyzed to compare the meteorological data three days prior to admission between patients with positive sputum pathogen cultures and those without. Logistic regression models were employed to investigate the association between meteorological parameters and the status of sputum pathogen cultures in patients with AECOPD and respiratory infections. Sensitivity analyses was conducted among the hospitalized patients from 2013 to 2016 and 2017-2019. Stratified analysis was performed to explore the factors affecting the effect of temperature differences and their interactions. RESULTS: 578(42.19%) cases had a positive sputum culture report indicating pathogen growth. 323 cases were found with Gram-negative bacteria, 160 with Gram-positive bacteria, and 114 with fungi. Uni-variate analysis revealed statistical differences in DTD three days prior to admission (DTD-3d) between the positive and negative sputum culture groups (p = 0.019). Multivariate analysis indicated that an increase in the risk of positive sputum pathogen cultures was associated with greater DTD three days before admission (DTD-3d), with OR1.657 (95%CI [ 1.328-1.981]). The risk of positive sputum pathogen cultures was higher in groups with greater DTD-3d. The findings were consistent across different admission periods. Stratified analysis showed that patients without respiratory failure were more affected by DTD-3d, and an interaction effect was observed (p < 0.001). CONCLUSION: In coastal areas, the diurnal temperature difference three days prior to admission affects the sputum pathogen status in AECOPD patients with respiratory infections.

Causal association between 25-hydroxyvitamin D status and cataract development: A two-sample Mendelian randomization study.

BACKGROUND: Vitamin deficiencies are linked to various eye diseases, and the influence of vitamin D on cataract formation has been noted in prior research. However, detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce. AIM: To explore a possible causal link between cataracts and vitamin D. METHODS: In this study, we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization. Our analytical approach included inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. The primary analyses utilized IVW with random effects, supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger. MR-Egger was also applied for pleiotropy testing. Additionally, a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms. RESULTS: The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts (OR = 1.11, 95%CI: 1.00-1.22; P = 0.032). The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity (P > 0.05), and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis (P > 0.05). Furthermore, a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms. CONCLUSION: There is a potential causal link between 25-(OH)D levels and the development of cataracts, suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation. Further experimental research is required to confirm these findings.

Prickly ash seeds can promote healthy production of sheep by regulating the rumen microbial community.

This study aimed to investigate the effect of prickly ash seeds (PAS) on the microbial community found in rumen microbes of Hu sheep by adding different percentages of prickly ash seeds and to carry out research on the relation between rumen flora and production performance. Twenty-seven male lambs of Hu sheep were classified into three groups based on the content of prickly ash seeds (PAS) fed for 90 days, i.e., 0%, 3%, and 6%. At the end of the feeding trial, rumen fluid samples were collected from six sheep in each group for 16S amplicon sequencing. The results showed that the addition of prickly ash seeds significantly increased both Chao1 and ACE indices (P < 0.05), and the differences between groups were greater than those within groups. The relative content of Bacteriodota decreased, and the relative content of Fusobacteriota, Proteobacteria, Acidobacteriota, and Euryarchaeota increased. The relative content of Papillibacter and Saccharofermentans was increased at the genus level, and the relative content of Bacteroides and Ruminococcus was decreased. The test group given 3% of prickly ash seeds was superior to the test group given 6% of prickly ash seeds. In addition, the addition of 3% of prickly ash seeds improved the metabolism or immunity of sheep. Fusobacteriota and Acidobacteriota were positively correlated with total weight, dressing percentage, and average daily gain (ADG) and negatively correlated with average daily feed intake (ADFI), feed-to-gain ratio (F/G), and lightness (L*). Methanobrevibacter and Saccharofermentans were positively correlated with ADG and negatively correlated with ADFI and L*. In conclusion, under the present experimental conditions, the addition of prickly ash seeds increased the abundance and diversity of rumen microorganisms in Hu sheep and changed the relative abundance of some genera. However, the addition of 6% prickly ash seeds may negatively affect the digestive and immune functions in sheep rumen.

Rumen Development of Tianhua Mutton Sheep Was Better than That of Gansu Alpine Fine Wool Sheep under Grazing Conditions.

The purpose of this experiment was to investigate the differences in rumen tissue morphology, volatile fatty acid content, and rumen microflora between Tianhua mutton sheep and Gansu alpine fine wool sheep under the same grazing conditions. Twelve 30-day-old lambs were randomly selected from two different flocks in Duolong Village and grazed together for a period of 150 days. The rumen tissue was fixed with 4% paraformaldehyde and brought back to the laboratory for H&E staining, the volatile fatty acid content of the rumen contents was detected by gas chromatography, and the rumen flora structure was sequenced by full-length sequencing of the bacterial 16S rRNA gene using the PacBio sequencing platform. The acetic acid and total acid contents of the rumen contents of Tianhua mutton sheep were significantly higher than those of Gansu alpine fine wool sheep (p < 0.05). The rumen papillae height of Tianhua mutton sheep was significantly higher than that of Gansu alpine fine wool sheep (p < 0.05). The diversity and richness of the rumen flora of Tianhua mutton sheep were higher than those of Gansu alpine fine wool sheep, and Beta analysis showed that the microflora structure of the two fine wool sheep was significantly different. At the phylum level, Firmicutes and Bacteroidetes dominated the rumen flora of Tianhua mutton sheep and Gansu alpine fine wool sheep. At the genus level, the dominant strains were Christensenellaceae_R_7_group and Rikenellaceae_RC9_gut_group. LEfSe analysis showed that Prevotella was a highly abundant differential species in Tianhua mutton sheep and lachnospiraccac was a highly abundant differential species in Gansu alpine fine wool sheep. Finally, both the KEGG and COG databases showed that the enrichment of biometabolic pathways, such as replication and repair and translation, were significantly higher in Tianhua mutton sheep than in Gansu alpine fine wool sheep (p < 0.05). In general, there were some similarities between Tianhua mutton sheep and Gansu alpine fine wool sheep in the rumen tissue morphology, rumen fermentation ability, and rumen flora structure. However, Tianhua mutton sheep had a better performance in the rumen acetic acid content, rumen papillae height, and beneficial bacteria content. These differences may be one of the reasons why Tianhua mutton sheep are more suitable for growing in alpine pastoral areas than Gansu alpine fine wool sheep.

Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway.

The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.

Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24 dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

The prevention effect of Limosilactobacillus reuteri on acute kidney injury by regulating gut microbiota.

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.