Diagnostic Value of Superb Microvascular Imaging of the Rotator Cuff Interval for the Early Diagnosis of Frozen Shoulder.

Purpose: To explore the early diagnostic value of superb microvascular imaging (SMI) features within the rotator cuff gap for frozen shoulder. Patients and Methods: This prospective study enrolled patients with acute early-stage frozen shoulder seeking treatment at Zhabei Central Hospital in Jing'an District, Shanghai, between July 2021 and December 2022 were enrolled in this study. Healthy controls were collected in a 1:1 ratio from the same hospital's physical examination center. All participants underwent SMI and power Doppler ultrasound (PDUS) of the rotator cuff gap. Results: The study included 79 patients with frozen shoulder and 77 healthy controls. Compared with the healthy control group, the patient group had a higher proportion of hypoechoic rotator cuff gap (81.0% vs 48.1%, P<0.001), a thicker coracohumeral ligament (2.60±1.01 vs 2.03±0.97, P<0.001), a thicker glenohumeral joint capsule (3.10±0.99 vs 2.46±1.17, P<0.001), and elevated blood grading using SMI (P<0.001) and PDUS (P=0.014). The highest area under the curve (AUC) was observed for SMI blood flow grading (AUC=0.824, 95% CI: 0.755-0.880, P<0.001), resulting in 82% sensitivity and 77% specificity when using a cutoff of 1. SMI blood flow grading was associated with external rotation <30° (P=0.007) and abduction <30° (P=0.013) but not with internal rotation <30° (P=0.630) or flexion <30° (P=0.562). Conclusion: The grading of SMI blood flow may emerge as a valuable predictive indicator for the early stages of frozen shoulder. This simple ultrasound technique holds the potential to enhance the diagnostic process, enabling early initiation of treatment and potentially improving patient outcomes.

NFMPAtt-Unet: Neighborhood Fuzzy C-means Multi-scale Pyramid Hybrid Attention Unet for medical image segmentation.

Medical image segmentation is crucial for understanding anatomical or pathological changes, playing a key role in computer-aided diagnosis and advancing intelligent healthcare. Currently, important issues in medical image segmentation need to be addressed, particularly the problem of segmenting blurry edge regions and the generalizability of segmentation models. Therefore, this study focuses on different medical image segmentation tasks and the issue of blurriness. By addressing these tasks, the study significantly improves diagnostic efficiency and accuracy, contributing to the overall enhancement of healthcare outcomes. To optimize segmentation performance and leverage feature information, we propose a Neighborhood Fuzzy c-Means Multiscale Pyramid Hybrid Attention Unet (NFMPAtt-Unet) model. NFMPAtt-Unet comprises three core components: the Multiscale Dynamic Weight Feature Pyramid module (MDWFP), the Hybrid Weighted Attention mechanism (HWA), and the Neighborhood Rough Set-based Fuzzy c-Means Feature Extraction module (NFCMFE). The MDWFP dynamically adjusts weights across multiple scales, improving feature information capture. The HWA enhances the network's ability to capture and utilize crucial features, while the NFCMFE, grounded in neighborhood rough set concepts, aids in fuzzy C-means feature extraction, addressing complex structures and uncertainties in medical images, thereby enhancing adaptability. Experimental results demonstrate that NFMPAtt-Unet outperforms state-of-the-art models, highlighting its efficacy in medical image segmentation.

[Expression and clinical significance of serum squamous cell carcinoma antigen（SCCAg） in sinonasal inverted papilloma].

Objective:To compare the expression levels of SCCAg in inverted papilloma of the nasal sinuses and other sinuses and sinus masses. To investigate the correlation between the expression of SCCAg in sinonasal inverted papilloma and outcome. Methods:Sixty-eight patients with unilateral nasal and sinus masses admitted to the Otorhinolaryngology Center of the Affiliated Hospital of Guangdong Medical University from September 2020 to February 2023 were randomly selected, including 31 patients with inverted papilloma （experimental group） and 37 patients with unilateral nasal and sinus masses excluding inverted papilloma （control group）. The application of automatic chemiluminescence immunoassay to test the serum SCCAg of the experimental group before surgery and 1 week after surgery, and the control group to measure the serum SCCAg before surgery. Clinical data were also collected. Results:There was no significant difference between the experimental group and the control group in gender and preoperative peripheral blood inflammatory indicators. However, there was significant difference in age and preoperative serum SCCAg level（P<0.001）. The serum SCCAg levels of the experimental group before and 1 week after surgery were significantly different（P<0.001）. The positive predictive value, negative predictive value, sensitivity and specificity of serum SCCAg in the diagnosis of varus papilloma were 92.6%, 85.4%, 77.4%, 94.6% and 0.72, respectively. The effect of serum SCCAg in the diagnosis of varus papilloma was analyzed by drawing the subject's working characteristic curve, and the area under the curve was 0.968（P<0.001）. When serum SCCAg greater than 2.7 ng/mL, the sensitivity and specificity were 67.7% and 94.6%, respectively. There was statistical significance in serum SCCAg levels between patients with and without recurrence（P<0.05）. Conclusion:The level of SCCAg in unilateral nasal and sinuses tumors, excluding squamous cell carcinoma, was significantly increased in inverted papilloma. The detection of serum SCCAg can be used as a simple and cost-effective auxiliary diagnostic tool for patients with nasal inverted papilloma before operation. Significant differences in preoperative and postoperative levels can be used for preliminary evaluation of surgical efficacy. Monitoring the serum SCCAg level in patients with inverted papilloma after surgery can predict recurrence and provide a simple and feasible method for postoperative follow-up.

Effects of climate warming on soil nitrogen cycles and bamboo growth in core giant panda habitat.

Climate change can pose a significant threat to terrestrial ecosystems by disrupting the circulation of soil nitrogen. However, experimental analyses on the effect of climate change on soil nitrogen cycles and the implications for the conservation of key wildlife species (i.e., the giant panda, Ailuropoda melanoleuca) remain understudied. We investigated the effects of a 1.5 °C, 3 °C, and 4.5 °C temperature increase on nitrogen distribution in different soil layers of bamboo forest via an in-situ experiment and assessed the implications for the growth and survival of arrow bamboo (Bashania faberi), a critical food resource for giant pandas. Our results showed that warming treatments generally increased soil N content, while effects differed between surface soil and subsurface soil and at different warming treatments. Particularly an increase of 1.5 °C raised the subsurface soil NO3-N content, as well as the content of N in bamboo leaves. We found a significant positive correlation between the subsurface soil NO3-N content and the N content of arrow bamboo. An increase of 3-4.5 °C raised the content of total N and NO3-N in the surface soil and led to a reduction in the total aboveground biomass and survival rate of arrow bamboo. Limited warming (e.g., the increase of 0-1.5 °C) may promote the soil N cycle, raise the N-acetylglucosaminidase (NAG) enzyme activity, increase NO3-N in subsurface soil, increase the N content of bamboo, and boost the biomass of bamboo - all of which could be beneficial to giant panda survival. However, higher warming (e.g., an increase of 3-4.5 °C) resulted in mass death of bamboo and a large reduction in aboveground biomass. Our findings provide a cautiously optimistic scenario for bamboo forest ecosystems under low levels of warming over a short period of time, but risks from higher levels of warming may be serious, especially considering the unpredictability of global climatic change.

miR-155 promotes Th17 differentiation by targeting FOXP3 to aggravate inflammation in MRSA pneumonia.

BACKGROUND: Previous researches have clarified that miR-155 is increased in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and modulates Th9 differentiation. Like Th9 cells, Th17 cells were also a subset of CD4+ T cells and involved in MRSA pneumonia progression. This work aimed to investigate the role and mechanism of miR-155 in Th17 differentiation. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from children with MRSA pneumonia and bronchial foreign bodies. MRSA-infected murine model was established followed by collecting BALF and lung tissues. qRT-PCR, ELISA and flow cytometry were performed to examine the mRNA expression and concentration of IL-17 and the number of Th17 cells in above samples. HE and ELISA were used to evaluate inflammatory responses in lung. Furthermore, CD4+ T cells were isolated from BALF of children for in vitro experiments. After treatments with miR-155 mimic/inhibitor, the roles of miR-155 in Th17/IL-17 regulation were determined. The downstream of miR-155 was explored by qRT-PCR, western blotting, dual luciferase reporter analysis and RIP assay. RESULTS: The levels of IL-17 and the proportion of Th17 cells were increased in children with MRSA pneumonia. A similar pattern was observed in MRSA-infected mice. On the contrary, IL-17 neutralization abolished the activation of Th17/IL-17 induced by MRSA infection. Furthermore, IL-17 blockade diminished the inflammation caused by MRSA. In vitro experiments demonstrated miR-155 positively regulated IL-17 expression and Th17 differentiation. Mechanistically, FOXP3 was a direct target of miR-155. miR-155 inhibited FOXP3 level via binding between FOXP3 and Argonaute 2 (AGO2), the key component of RNA-induced silencing complex (RISC). FOXP3 overexpression reversed elevated IL-17 levels and Th17 differentiation induced by miR-155. CONCLUSIONS: miR-155 facilitates Th17 differentiation by reducing FOXP3 through interaction of AGO2 and FOXP3 to promote the pathogenesis of MRSA pneumonia. IL-17 blockade weakens the inflammation due to MRSA, which provides a nonantibiotic treatment strategy for MRSA pneumonia.

Removal of ciprofloxacin by biosulfurized nano zero-valent iron (BP-S-nZVI) activated peroxomonosulfate: Influencing factors and degradation mechanism.

Agglomeration and passivation restrict the using zero-valent iron nanoparticles (nZVI). Enhancing the reactivity of nZVI is often accomplished by sulfurization. In this work, nZVI was sulfurized using SRB to produce biosulfurized nano zero-valent iron (BP-S-nZVI), which was then utilized as a catalyst to investigating its performance in an advanced oxidation process based on activated peroxomonosulfate (PMS). When the S/Fe was 0.05, 0.4 g/L of catalyst and 0.5 mM PMS were added to a 20 mg/L ciprofloxacin solution. In 120 min, a 90.4% clearance rate was reached. When the initial pH of the solution was within the range of 3-11, all exhibited acceptable degradation performance and were minimally affected by co-existing anions. In this activation system, hydroxyl, superoxide and sulfate radicals (•OH, O2•- and SO4•-, respectively) have been proven to be the main active species. Seven intermediates in the degradation process of CIP were identified by LC-MS analysis and two possible degradation pathways were proposed. In addition, the degradation rate of CIP was still able to reach 87.0% after five cycles, and the removal rate remained unchanged in the CIP solution with actual water samples as background. This study demonstrated that BP-S-nZVI as a catalyst for the activation of PMS for CIP degradation can still show good reactivity, which provides more possibilities for the practical application of BP-S-nZVI in the degradation of pollutants.

A Spatially Stable Crystal-Particle Gel to Trap Patchouli Oil for Efficient Colonic Drug Delivery.

Patchouli oil has exhibited remarkable efficacy in the treatment of colitis. However, its volatility and potential irritancy are often drawbacks when extensively used in clinical applications. Oil gel is a semisolid and thermoreversible system that has received extensive interest for its solubility enhancement, inhibition of bioactive component recrystallization, and the facilitation of controlled bioactive release. Therefore, we present a strategy to develop an oil gel formulation that addresses this multifaceted problem. Notably, a patchouli oil gel formulation was designed to solidify and trap patchouli oil into a spatially stable crystal-particle structure and colonic released delivery, which has an advantage of the stable structure and viscosity. The patchouli oil gel treatment of zebrafish with colitis improved goblet cells and decreased macrophages. Additionally, patchouli oil gel showed superior advantages for restoring the tissue barrier. Furthermore, our investigative efforts unveiled patchouli oil's influence on TRP channels, providing evidence for its potential role in mechanisms of anti-inflammatory action. While the journey continues, these preliminary revelations provide a robust foundation for considering the adoption of patchouli oil gel as a pragmatic intervention for managing colitis.

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid.

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

A Comprehensive Analysis of the Peanut SQUAMOSA Promoter Binding Protein-like Gene Family and How AhSPL5 Enhances Salt Tolerance in Transgenic Arabidopsis.

SPL (SQUAMOSA promoter binding protein-like), as one family of plant transcription factors, plays an important function in plant growth and development and in response to environmental stresses. Despite SPL gene families having been identified in various plant species, the understanding of this gene family in peanuts remains insufficient. In this study, thirty-eight genes (AhSPL1-AhSPL38) were identified and classified into seven groups based on a phylogenetic analysis. In addition, a thorough analysis indicated that the AhSPL genes experienced segmental duplications. The analysis of the gene structure and protein motif patterns revealed similarities in the structure of exons and introns, as well as the organization of the motifs within the same group, thereby providing additional support to the conclusions drawn from the phylogenetic analysis. The analysis of the regulatory elements and RNA-seq data suggested that the AhSPL genes might be widely involved in peanut growth and development, as well as in response to environmental stresses. Furthermore, the expression of some AhSPL genes, including AhSPL5, AhSPL16, AhSPL25, and AhSPL36, were induced by drought and salt stresses. Notably, the expression of the AhSPL genes might potentially be regulated by regulatory factors with distinct functionalities, such as transcription factors ERF, WRKY, MYB, and Dof, and microRNAs, like ahy-miR156. Notably, the overexpression of AhSPL5 can enhance salt tolerance in transgenic Arabidopsis by enhancing its ROS-scavenging capability and positively regulating the expression of stress-responsive genes. These results provide insight into the evolutionary origin of plant SPL genes and how they enhance plant tolerance to salt stress.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Efficient Cr(VI) removal by pyrite/porous biochar: Critical role of potassium salt and sulphur.

The excessive accumulation of hexavalent chromium (Cr(VI)) in the environment poses a risk to environment and human health. In the present study, a potassium bicarbonate-modified pyrite/porous biochar composite (PKBC) was prepared in a one-step process and applied for the efficient removal of Cr(VI) in wastewater. The results showed that PKBC can significantly remove Cr(VI) within 4 h over a wide range of pH (2-11). Meanwhile, the PKBC demonstrated remarkable resistance towards interference from complex ions. The addition of potassium bicarbonate increased the pore structure of the material and promoted the release of Fe2+. The reduction of Cr(VI) in aqueous solution was primarily attributed to the Fe(II)/Fe(III) redox cycle. The sulphur species achieved Fe(II)/Fe(III) cycle through electron transfer with iron, thus ensuring the continuous reduction capacity of PKBC. Besides, the removal rate was also maintained at more than 85% in the actual water samples treatment process. This work provides a new way to remove hexavalent chromium from wastewater and demonstrates the potential critical role of potassium bicarbonate and sulphur.

The complete mitochondrial genome of the Baishanzu horned toad Boulenophrys baishanzuensis (Anura: Megophryidae).

The mitochondrial genome (mitogenome) of Boulenophrys baishanzuensis (Anura: Megophryidae) was sequenced by the Illumina platform. The assembled circular mitogenome of B. baishanzuensis had a total length of 17,040 bp, with a GC content of 41.25%. It consisted of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and a D-loop region. The majority of the PCGs were encoded by the H-strand, while one PCG (nad6) and eight tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser2, tRNA-Glu, and tRNA-Pro) were encoded in the L-strand. Phylogenetic analysis revealed that the newly sequenced species formed a clade with other Boulenophrys species, while the genus Boulenophrys itself formed a sister group with the genus Atympanophrys.

A novel approach involving reversed placement of endobronchial valves combined with retrograde methylene blue instillation for the localization of multifocal bronchopleural fistula.

The bronchopleural fistula (BPF) is a pathological communication between the bronchus and the pleural space. Diagnosing BPF poses a significant challenge for physicians, particularly when identifying multifocal BPFs. Traditionally, retrograde instillation of methylene blue (MB) into the pleural cavity with simultaneous observation with a bronchoscope has been used to locate a BPF. However, MB instillation is not effective in identifying multifocal BPFs. In this article, we report a new method for locating multifocal BPFs which involves placing the endobronchial valve (EBV) in reverse combined with retrograde MB instillation. First, the thoracic cavity is filled with MB solution. Then, using bronchoscopy, the location of a BPF can be identified as the MB solution flows into the bronchus. Secondly, an EBV is deployed in reverse in the bronchus where the identified BPF is located. Retrograde MB instillation is then repeated to locate any additional BPFs until no new ones are found. Two cases were reported using this novel method to identify multifocal BPFs, and each case was ultimately diagnosed with 2 BPFs. After precisely locating all the BPFs, the EBVs are then removed and placed forward in the target bronchi for treating the BPFs. During the follow-up period, no recurrence of BPFs was observed. We conclude that reversed placement of EBVs combined with retrograde MB instillation appears to be an effective approach for locating multifocal BPFs.

Stereodivergent Protein Engineering of Fatty Acid Photodecarboxylase for Light-Driven Kinetic Resolution of Sec-Alcohol Oxalates.

Stereodivergent engineering of one enzyme to create stereocomplementary variants for synthesizing optically pure molecules with tailor-made (R) or (S) configurations on an optional basis is highly desirable and challenging. This study aimed to engineer fatty acid photodecarboxylase from Chlorella variabilis (CvFAP) using the focused rational iterative site-specific mutagenesis (FRISM) strategy to obtain two highly stereocomplementary variants with excellent selectivity (both giving products with up to 99 % e.e.). These variants were used for the CvFAP-catalyzed light-driven kinetic resolution of oxalates or oxamic acids prepared from the corresponding sec-alcohols or amines, providing a new biotransformation process for preparing chiral sec-alcohols and amines. Molecular dynamics simulation, kinetic data and transient spectra revealed the source of selectivity. This study represents the first example of the kinetic resolution of sec-alcohols or amines catalyzed by a pair of stereocomplementary CvFAPs.

Global hidden spillover effects among concurrent green initiatives.

Concurrently implemented green initiatives to combat global environmental crises may be curtailed or even sacrificed given the ongoing global economic contraction. We collected empirical data and information about green initiatives from 15 sites or countries worldwide. We systematically explored how specific policy, intended behaviors, and gains of given green initiative may interact with those of other green initiatives concurrently implemented in the same geographic area or involving the same recipients. Surprisingly, we found that spillover effects were very divergent: one initiative could reduce the gain of another by 22 % âˆ¼ 100 %, representing alarming losses, while in other instances, substantial co-benefits could arise as one initiative can increase the gain of another by 9 % âˆ¼ 310 %. Leveraging these effects will help countries keep green initiatives with significant co-benefits but stop initiatives with substantial spillover losses in the face of widespread budget cuts, better meeting the United Nations' sustainable development goals.

The protease Lon prolongs insect lifespan by responding to reactive oxygen species and degrading mitochondrial transcription factor A.

Diapause is a widespread adaptation of insects that enables them to survive during unfavorable seasons and is characterized by suppressed metabolism and increased lifespan. Previous works have demonstrated that high levels of reactive oxygen species (ROS) and hypoxia-inducible factor-1α (HIF-1α) in the pupal brain of the moth Helicoverpa armigera induce diapause and extend lifespan by downregulating mitochondrial transcription factor A (TFAM). However, the molecular mechanisms of ROS-HIF-1α regulating metabolic activity to extend lifespan are still poorly understood. Here, we show that the mitochondrial abundance in diapause-type pupal brains is markedly lower than that in their nondiapause-type pupae, suggesting that ROS-HIF-1α signaling negatively regulates the number of mitochondria. The protease Lon, a major mitochondrial matrix protease, can respond to ROS signals. It is activated by transcription factor HIF-1α, which specifically binds the LON promoter to promote its expression. A high level of LON mediates the degradation of TFAM, which is a crucial factor in regulating mitochondrial abundance and metabolic activity. We believe this is the first report that a previously unrecognized regulatory pathway, ROS-HIF-1α-LON-TFAM, reduces mitochondrial activity to induce diapause, extending insect lifespan.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy.

Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO2 (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O2) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.

Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells.

BACKGROUND: Liver fibrosis is the common pathological process associated with the occurrence and development of various chronic liver diseases. At present, there is still a lack of effective prevention and treatment methods in clinical practice. Hepatic stellate cell (HSC) plays a key role in liver fibrogenesis. In recent years, the study of liver fibrosis targeting HSC autophagy has become a hot spot in this research field. Angiotensin-converting enzyme 2 (ACE2) is a key negative regulator of renin-angiotensin system, and its specific molecular mechanism on autophagy and liver fibrosis needs to be further explored. AIM: To investigate the effect of ACE2 on hepatic fibrosis in mice by regulating HSC autophagy through the Adenosine monophosphate activates protein kinases (AMPK)/mammalian target of rapamycin (mTOR) pathway. METHODS: Overexpression of ACE2 in a mouse liver fibrosis model was induced by injection of liver-specific recombinant adeno-associated virus ACE2 vector (rAAV2/8-ACE2). The degree of liver fibrosis was assessed by histopathological staining and the biomarkers in mouse serum were measured by Luminex multifactor analysis. The number of apoptotic HSCs was assessed by terminal deoxynucleoitidyl transferase-mediated dUTP nick-end labeling (TUNEL) and immunofluorescence staining. Transmission electron microscopy was used to identify the changes in the number of HSC autophagosomes. The effect of ACE2 overexpression on autophagy-related proteins was evaluated by multicolor immunofluorescence staining. The expression of autophagy-related indicators and AMPK pathway-related proteins was measured by western blotting. RESULTS: A mouse model of liver fibrosis was successfully established after 8 wk of intraperitoneal injection of carbon tetrachloride (CCl4). rAAV2/8-ACE2 administration reduced collagen deposition and alleviated the degree of liver fibrosis in mice. The serum levels of platelet-derived growth factor, angiopoietin-2, vascular endothelial growth factor and angiotensin II were decreased, while the levels of interleukin (IL)-10 and angiotensin- (1-7) were increased in the rAAV2/8-ACE2 group. In addition, the expression of alpha-smooth muscle actin, fibronectin, and CD31 was down-regulated in the rAAV2/8-ACE2 group. TUNEL and immunofluorescence staining showed that rAAV2/8-ACE2 injection increased HSC apoptosis. Moreover, rAAV2/8-ACE2 injection notably decreased the number of autophagosomes and the expression of autophagy-related proteins (LC3I, LC3II, Beclin-1), and affected the expression of AMPK pathway-related proteins (AMPK, p-AMPK, p-mTOR). CONCLUSION: ACE2 overexpression can inhibit HSC activation and promote cell apoptosis by regulating HSC autophagy through the AMPK/mTOR pathway, thereby alleviating liver fibrosis and hepatic sinusoidal remodeling.