Genetically Engineered Membrane-Coated Nanoparticles for Enhanced Prostate-Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration-Resistant Prostate Cancer.

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.

TRPV1/cPLA2/AA pathway contributes to ferroptosis-mediated acute liver injury in heatstroke.

With the increasing frequency of global heatwaves, the incidence of heatstroke (HS) is significantly rising. The liver plays a crucial role in metabolism and is an organ highly sensitive to temperature. Acute liver injury (ALI) frequently occurs in patients with HS, yet the exact mechanisms driving ALI in HS are still unknown. In this basic study, we investigated the specific molecular mechanisms by which cytosolic phospholipase A2 (cPLA2) mediates ferroptosis, contributing to the development of ALI following HS. We utilized a mouse model of HS and divided the mice into healthy control and HS groups for a series of experiments. Firstly, we assessed oxidative damage markers in tissues and cells, as well as ferroptosis biomarkers. Additionally, we conducted a non-targeted metabolomics analysis to validate the role of key enzymes in metabolism and the ferroptosis pathway. Our results indicated that ferroptosis contributed to the progression of ALI after HS. Administering the ferroptosis inhibitor liproxstatin-1 (10 mg/kg) post-HS onset significantly inhibits HS-induced ALI progression. Mechanistically, heatstroke triggered cPLA2 activation and increased the levels of its metabolic product, arachidonic acid, thereby further promoted the occurrence of ferroptosis. Furthermore, heatstroke mediated cPLA2 activation might involve enhancing transient receptor potential vanilloid subtype 1 (TRPV1) receptor function. Overall, these results highlighted the critical role that cPLA2-mediated ferroptosis plays in the development of ALI following HS, indicating that inhibiting cPLA2 may present a novel therapeutic approach to prevent ALI after HS by limiting liver cell death.

Silk fibroin catheter with stable bioinspired inner-surfaces for inhibition of bioadhesion.

Biofilm formation on indwelling medical devices such as catheters and ventilators due to the adhesion of bacteria poses significant challenges in healthcare. Surface modification with micro- and nano-structures offers a promising strategy to prevent bioadhesion and is safer than surface chemical modification approaches. Here, catheters were prepared using silk fibroin (SF) hydrogels and an infusion molding method, with the inner surface featuring a micropapillae structure inspired by lotus leaves (SF-CMP). After phenylethanol (PEA) fumigation treatment, the resulting catheters (SF-CMP PEA) displayed improved swelling resistance and mechanical properties compared to methanol-treated catheters (SF-CMP MeOH). PEA was more efficient than methanol in controlling the size, distribution, and content of silk crystalline ß-sheet blocks and thus the swelling and mechanical properties. Moreover, the micro-papillae structure on SF-CMP PEA remained stable over 35 days in solution, in contrast to SF-CMP MeOH, which lasted <7 days. SF-CMP PEA exhibited repellent effects against E. coli and S. aureusin vitro, and low cytotoxicity to the endothelial cells cultured on the unpatterned surface. Additionally, subcutaneous implantation studies showed reduced inflammation around the micropatterned samples compared to controls with a plain, unpatterned surface. The unique properties of SF-based materials, including tunable structures, biocompatibility, degradation, and drug-loading capability make them an attractive material for anti-bioadhesion in applications ranging from indwelling medical devices to tissue engineering scaffolds.

Extract of Scutellaria baicalensis and Lonicerae flos improves growth performance, antioxidant capacity, and intestinal barrier of yellow-feather broiler chickens against Clostridium perfringens.

In this study, we aimed to investigate the effect of Scutellaria baicalensis and Lonicerae Flos (SL) extract on the growth performance and intestinal health of yellow-feather broilers following a Clostridium perfringens challenge. In total, 600 one-day-old yellow-feather broilers were divided into five treatments (6 replicate pens of 20 birds per treatment), including a control (Con) group fed a basal diet and the infected group (iCon) fed a basal diet and infected with Clostridium perfringens, the other 3 groups receiving different doses of SL (150, 300, and 450 mg/kg) and infected with Clostridium perfringens. The total experimental period was 80 d. When the birds were 24-days-old, a subclinical necrotizing enteritis model was induced by orally inoculating the birds with 11,000 oocysts of mixed Eimeria species on d 24, followed by C. perfringens (108 CFU/mL) from d 28 to 30. The birds were evaluated for parameters such as average weight gain (AWG), average daily feed intake (ADFI), mortality, feed conversion ration (FCR), intestinal lesion score, intestinal C. perfringens counts, and villus histomorphometry. Results indicated that C. perfringens infection led to reduced AWG and the levels of tight junction proteins, increased the FCR, ileum E. coli load, and intestinal permeability, causing damage to the intestinal mucosal barrier (P < 0.05). Compared with the infected group, supplementing 300 mg/kg of SL significantly increased AWG at 43 to 80 d, the ratio of villus height to crypt depth in the jejunum and ileum at 35 d, and the activity of superoxide dismutase (SOD) in serum. It also significantly reduced the FCR at 22 to 42 d, intestinal lesion score, and the amount of C. perfringens in the ileum (P < 0.05). Additionally, compared with the infected group, the addition of 300 mg/kg SL significantly increased mRNA levels of claudin-2, claudin-3, mucin-2, and toll-like receptor 2 (TLR-2) in the ileum of infected birds at 35 d of age. In conclusion, supplementation with SL extract could effectively mitigate the negative effects of C. perfringens challenge by improving intestinal barrier function and histomorphology, positively influencing the growth performance of challenged birds.

Pu-erh tea theabrownin improves the ovarian function and gut microbiota in laying hens.

Studies have reported that theabrownin can moderate the lipid metabolism and intestinal microbiota, thereby affecting the health of humans and model animals, however the research on laying hens is scarce. The present study aimed to investigate the effects of dietary theabrownin supplementation on lipid metabolism, microbial composition and ovarian function in laying hens. A total of 80 laying hens (25 wk of age) were fed with normal diet (CON) and normal diet +100 mg/kg theabrownin (PT group) for 12 wk. The results showed that the addition of theabrownin enhanced villus height of duodenum and decreased crypt depth of jejunum (P < 0.05). At the same time, compared with CON, the concentration of IL-6 and the mRNA expression of IL-1ß and IL-6 were decreased significantly in PT group (P < 0.05). Dietary theabrownin reduced the concentration of total cholesterol and glycerol, while decreased lipid droplet optical density in liver (P < 0.05). Compared with CON group, the mRNA expression of PPARγ, HMG-CoAS, ACC were down-regulated and the mRNA expression of CYP8B1 was up-regulated in PT group (P < 0.05). The ACE, Chao1 and Observed_species indexes in cecum microbiota were increased by PT group intervention (P < 0.05). Dietary PT supplementation enhanced the relative abundance of Firmicutes (phylum), Lactobacillus (genus) and the Firmicutes to Bacteroidetes ratio, and reduced the relative abundance of Bacteroidetes (phylum) in cecum (P < 0.05). The organic acids and its derivatives were up-regulated by theabrownin intervention in serum metabolites (P < 0.05). Dietary theabrownin supplementation resulted in higher mRNA expression of Bcl-2 and SIRT1 in ovary and increased the concentration of estradiol in serum (P < 0.05). These discovering indicated that dietary theabrownin supplementation enhanced the intestinal function and influenced serum metabolism by improving intestinal morphology, microbiota community structure and reducing the concentration and expression of inflammatory cytokines in intestine. Dietary theabrownin reduced hepatic lipid deposition and it also decreased the cell apoptosis rate to improve ovarian function and egg weight which were associated with the SIRT1 pathway.

SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.

Effects of Long-Term Coated Sodium Butyrate Supplementation on the Intestinal Health and Colonization of Cecal Salmonella of Laying Hens Infected with Salmonella enteritidis.

Salmonella enterica ser. Enteritidis (S. Enteritidis) is widely found in chickens and eggs, and it can potentially induce human illness. The investigation in this study centers on the impacts of long-term dietary supplementation with coated sodium butyrate (CSB) on intestinal well-being and the colonization of cecum Salmonella in laying hens infected with S. Enteritidis. We segregated a total of 120 Lohmann laying hens aged 51 weeks into four treatment categories: 0 (CON), 300 (CSB1), 500 (CSB2), and 800 (CSB3) mg/kg of CSB, supplemented with CSB from the first day of the experiment. A 24-week observation process was carried out for each laying hen. The S. Enteritidis was orally administered to all chickens on the morning of the first and third days of week 22 of the trial. After the S. Enteritidis challenge, egg production decreased the most in the CON group. Compared to the CON group, the three doses of CSB significantly improved egg production after the S. Enteritidis challenge (PANOVA < 0.05). S. Enteritidis challenge increased plasma DAO activity, but CSB supplementation reduced plasma DAO activity (Plinear < 0.05). The S. Enteritidis challenge disrupted intestinal villi morphology; compared to the CON group, the three dosages of CSB resulted in an increase in villus height (VH) and the ratio of villus height to crypt depth (V/C) in the duodenum, jejunum, and ileum of infected laying hens (Plinear < 0.05), with a significant increase in jejunal villus height (PANOVA < 0.05). A decrease in ileal crypt depth was also observed (Plinear < 0.05). CSB2 and CSB3 markedly increased the content of butyric acid in the cecum (PANOVA < 0.05). Additionally, in contrast to those in the CON group, the propionic acid content in the CSB supplementation group increased (Plinear < 0.05). Compared with those in the CON group, mRNA relative expression of the IL-6 and IL-1ß in jejunum (Plinear < 0.05) and mRNA relative expression of the IL-1ß in ileum (PANOVA < 0.05) were significantly lower, and mRNA relative expression of the IL-10 in ileum (Plinear < 0.05) were significantly higher in the CSB group. In addition, in contrast to the CON group, the CSB supplementation group significantly upregulated mRNA relative expression of the ZO-1 and CLDN1 (PANOVA < 0.05). Additionally, CSB supplementation reduced the number of Salmonella and increased the number of Lactobacilli in the cecum (Plinear < 0.05) and tended to increase the total bacteria count (Plinear = 0.069) and reduce the E. coli count (Plinear = 0.081). In conclusion, long-term dietary supplementation with coated sodium butyrate can alleviate intestinal injury and the colonization of cecum Salmonella in laying hens infected with S. Enteritidis.

All-trans retinoic acid pretreatment of mesenchymal stem cells enhances the therapeutic effect on acute kidney injury.

A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.

IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease.

Podocyte apoptosis or loss is the pivotal pathological characteristic of diabetic kidney disease (DKD). Insulin-like growth factor-binding protein 2 (IGFBP2) have a proinflammatory and proapoptotic effect on diseases. Previous studies have shown that serum IGFBP2 level significantly increased in DKD patients, but the precise mechanisms remain unclear. Here, we found that IGFBP2 levels obviously increased under a diabetic state and high glucose stimuli. Deficiency of IGFBP2 attenuated the urine protein, renal pathological injury and glomeruli hypertrophy of DKD mice induced by STZ, and knockdown or deletion of IGFBP2 alleviated podocytes apoptosis induced by high concentration of glucose or in DKD mouse. Furthermore, IGFBP2 facilitated apoptosis, which was characterized by increase in inflammation and oxidative stress, by binding with integrin α5 (ITGA5) of podocytes, and then activating the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury, including membrane potential decreasing, ROS production increasing. Moreover, ITGA5 knockdown or FAK inhibition attenuated the podocyte apoptosis caused by high glucose or IGFBP2 overexpression. Taken together, these findings unveiled the insight mechanism that IGFBP2 increased podocyte apoptosis by mitochondrial injury via ITGA5/FAK phosphorylation pathway in DKD progression, and provided the potential therapeutic strategies for diabetic kidney disease.

Macrophage-Derived Nanosponges Adsorb Cytokines and Modulate Macrophage Polarization for Renal Cell Carcinoma Immunotherapy.

Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8+ T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, macrophage-derived nanosponges are fabricated by M2 macrophage membrane-coated poly（lactic-co-glycolic acid）（PLGA）, which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges act like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as colony stimulating factor-1(CSF-1), transforming growth factor-ß（TGF-ß）, and Lnterleukin-10（IL-10）, thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8+ T cells. To further enhance the polarization reprogramming efficiency of TAMs, DSPE-PEG-M2pep is conjugated on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and the toll like receptors 7/8（TLR7/8） agonist, R848, is encapsulated in these nanosponges to induce M1 polarization, which result in significant efficacy against RCC. In addition, these nanosponges exhibit undetectable biotoxicity, making them suitable for clinical applications. In summary, a promising and facile strategy is provided for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.

A Light-Powered Micropump with Dynamic Collective Behavior for Reparation.

Inspired by the collective behaviors of active systems in nature, the collective behavior of micromotors has attracted more and more attention in recent years. However, little attention has been paid to the collective behavior of the immobilized micromotor, i.e., the micropump. In this paper, a unique pentacene-based micropump is reported, which demonstrates dynamic collective behavior activated by white light irradiation. The light irradiation may generate the photochemical reactions between pentacene and water, leading to the electroosmotic flow. As a result, this micropump is capable of pumping the surrounding solution inward along the substrate surface based on the electroosmosis mechanism. Intriguingly, the inward pumping causes the agglomeration of the tracer particles on the surface of the micropump. In addition, the aggregation can migrate following the change in the light irradiation position between two adjacent micropumps. Based on the aggregating and migrating behaviors of this pentacene-based micropump, we have achieved the conductivity restoration of the cracked circuit.

A novel microfluidic chip integrating with microcolumn array electrodes for rapid and ultrasensitive detection of alpha-fetoprotein.

BACKGROUND: Cancer posed a serious threat to human health, and early diagnosis of cancer biomarker was extremely important for the treatment and control of cancer. Electrochemistry-based assays were low-cost, responsive and easy to operate, but there were some challenges in terms of accuracy, detection limit, efficiency and portability. The combination of microfluidic devices and electrochemical methods was expected to construct a high-performance sensing platform, but long-time antigen-antibody incubation was still required. Therefore, a novel microfluidic chip needs to be developed, which has the advantages of good portability, short incubation time, high accuracy, low detection limit and great application to point-of-care testing. RESULTS: A microfluidic sensor based on microcolumn array electrodes was developed, in which microcolumns could create local mixed flow to reduce the incubation time of target molecules and enhance their interaction with the sensing interface. Besides, three dimensional Mxene fibers-gold nanoparticles (3D MF-Au) was modified on the microcolumn array electrodes to increase active sites and provide more electrolyte shuttle holes. The electrolyte turbulence caused by the microcolumn array electrodes could heighten the contact between the target molecules and sensing interface and accelerate the transfer of redox pairs, thus reducing the incubation time of the target molecules and improving the electrochemical responses in synergy with the 3D MF-Au. Herein, the detection of AFP was chosen as a model, and the microfluidic sensor possessed superior performance for analysis of AFP in the range of 0.1 pg mL-1 - 200 ng mL-1 with a low detection limit (LOD) of 0.0648 pg mL-1. SIGNIFICANCE: This microfluidic chip integrating with microcolumn array electrodes has been successfully implemented to detect AFP in human serum, and the results were consistent with that of electrochemical chemiluminescence method. The microfluidic chip provided a new strategy of portability, shortening incubation time and enhancing electrical signals for antigen detection of real samples, which showed great utilization potentiality in point-of-care testing.

Endosialin in Cancer: Expression Patterns, Mechanistic Insights, and Therapeutic Approaches.

Endosialin, also known as tumor endothelial marker 1 (TEM1) or CD248, is a single transmembrane glycoprotein with a C-type lectin-like domain. Endosialin is mainly expressed in the stroma, especially in cancer-associated fibroblasts and pericytes, in most solid tumors. Endosialin is also expressed in tumor cells of most sarcomas. Endosialin can promote tumor progression through different mechanisms, such as promoting tumor cell proliferation, adhesion and migration, stimulating tumor angiogenesis, and inducing an immunosuppressive tumor microenvironment. Thus, it is considered an ideal target for cancer treatment. Several endosialin-targeted antibodies and therapeutic strategies have been developed and have shown preliminary antitumor effects. Here, we reviewed the endosialin expression pattern in different cancer types, discussed the mechanisms by which endosialin promotes tumor progression, and summarized current therapeutic strategies targeting endosialin.

More Efficient Approach: Independent Diagnostic Value of Audiovisual Sexual Stimulation for Psychogenic Erectile Dysfunction.

The diagnostic value of audiovisual sexual stimulation (AVSS) for psychogenic erectile dysfunction (ED) is still unclear. We investigated the independent diagnostic value and optimal cut-off parameter of AVSS for psychogenic ED. All participants had received the AVSS test and nocturnal penile tumescence and rigidity (NPTR) monitoring at least twice. ED patients were divided into psychogenic ED and organic ED according to NPTR examination. The diagnostic accuracy of AVSS parameters was evaluated with the receiver operating characteristic (ROC) curve, and the Youden index was employed to determine the optimal diagnostic cut-off values. A total of 346 patients with ED and 60 healthy men were included in this study, among which 162 and 184 cases of psychogenic and organic ED were identified based on NPTR, respectively. When comparing the two ED groups, the area under the curve (AUC) of AVSS parameters was 0.85-0.89. Six-selected AVSS parameters could precisely diagnose psychogenic ED, exhibiting increased diagnostic specificity compared with corresponding sensitivity. When comparing psychogenic ED with the control group, the AUC of the tumescence of the tip was superior to the AUC other parameters (0.81 vs. 0.58, 0.66, 0.59, 0.53, 0.68), and the best determined diagnostic cut-off value was the tumescence of the tip < 29.87%. Independent AVSS could diagnose psychogenic ED objectively and effectively, and its diagnostic value was highest when 1.50% ≤ tumescence of the tip < 29.87%.

Femoral Tunnel Malposition, Increased Lateral Tibial Slope, and Decreased Notch Width Index Are Risk Factors for Non-Traumatic Anterior Cruciate Ligament Reconstruction Failure.

PURPOSE: To identify risk factors for patients who sustain nontraumatic anterior cruciate ligament reconstruction (ACLR) failure. METHODS: A retrospective analysis was performed on patients undergoing primary or revision ACLR in our institution between 2010 and 2018. Patients sustaining insidious-onset knee instability without history of trauma were identified as nontraumatic ACLR failure and assigned to the study group. The control group of subjects who showed no evidence of ACLR failure with minimum 48-month follow-up were matched in a 1:1 ratio based on age, sex, and body mass index. Anatomic parameters including tibial slope (lateral [LTS], medial [MTS]); tibial plateau subluxation (lateral [LTPsublx], medial [MTPsublx]); notch width index (NWI); and lateral femoral condyle ratio were measured with magnetic resonance imaging or radiography. Graft tunnel position was assessed using 3-dimensional computed tomography and reported in 4 dimensions: deep-shallow ratio (DS ratio) and high-low ratio for femoral tunnel, anterior-posterior ratio and medial-lateral ratio for tibial tunnel. Interobserver and intraobserver reliability were evaluated by the intraclass correlation coefficient (ICC). Patients' demographic data, surgical factors, anatomic parameters, and tunnel placements were compared between the groups. Multivariate logistic regression and receiver operating characteristic curve analysis was used to discriminate and assess the identified risk factors. RESULTS: A total of 52 patients who sustained nontraumatic ACLR failure were included and matched with 52 control subjects. Compared to patients with intact ACLR, those who sustained nontraumatic ACLR failure showed significantly increased LTS, LTPsublx, MTS, and deceased NWI (all P < .001). Moreover, the average tunnel position in the study group was significantly more anterior (P < .001) and superior (P = .014) at the femoral side and more lateral (P = .002) at the tibial side. Multivariate regression analysis identified LTS (odds ratio [OR] = 1.313; P = .028), DS ratio (OR = 1.091; P = .002), and NWI (OR = 0.813; P = .040) as independent predictors of nontraumatic ACLR failure. LTS appeared to be the best independent predictive factor (area under the curve [AUC] = 0.804; 95% confidence interval [CI], 0.721-0.887), followed by DS ratio (AUC = 0.803; 95% CI, 0.717-0.890), and NWI (AUC = 0.756; 95% CI, 0.664-0.847). The optimal cutoff values were 6.7° for increased LTS (sensitivity = 0.615, specificity = 0.923); 37.4% for increased DS ratio (sensitivity = 0.673, specificity = 0.885); and 26.4% for decreased NWI (sensitivity = 0.827, specificity = 0.596). Intraobserver and interobserver reliability was good to excellent, with ICCs ranging from 0.754 to 0.938 for all radiographical measurements. CONCLUSIONS: Increased LTS, decreased NWI, and femoral tunnel malposition are predictive risk factors for nontraumatic ACLR failure. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Medial Patellofemoral Complex Reconstruction (Combined Reconstruction of Medial Patellofemoral Ligament and Medial Quadriceps Tendon-Femoral Ligament) With Semitendinosus Autograft Resulted in Similar Clinical and Radiographic Outcomes to Medial Patellofemoral Ligament Reconstruction in Treating Recurrent Patellar Dislocation.

PURPOSE: To compare clinical and radiographic outcomes of medial patellofemoral ligament reconstruction (MPFL-R) and medial patellofemoral complex reconstruction (MPFC-R) for recurrent patellar dislocation. Outcome measures were compared based on the Insall-Salvati index. METHODS: Patients who were diagnosed with recurrent patellar dislocation and underwent either MPFL-R or MPFC-R (combined reconstruction of MPFL and medial quadriceps tendon-femoral ligament) were retrospectively analyzed. Group allocation was based on surgical procedure and patient characteristics were collected. Clinical assessments included patient-reported outcome measures (PROMs) and return-to-sports rates. Minimal clinically important difference analysis was performed. A subgroup analysis of PROMs was carried out between patients with an Insall-Salvati index ≤1.2 versus >1.2. The patellar tilt angle, lateral patellar displacement, and bisect offset ratio were measured pre- and postsurgery. Functional failures and complications were assessed. RESULTS: Overall, 70 patients (72 knees) in the MPFL-R group and 58 patients (61 knees) in the MPFC-R group were included. Patient characteristics were comparable between the groups. At a minimum follow-up of 24 (mean, 50.6 ± 22.1) months, all PROMs were substantially improved (P < .001), without significant intergroup differences. The percentages of patients reaching the minimal clinically important difference were similar after MPFL-R and MPFC-R: 98.6% versus 93.4% (International Knee Documentation Committee), 97.2% versus 98.4% (Lysholm), 98.6% versus 100% (Kujala), and 77.8% versus 72.1% (Tegner). The subgroup analysis based on patellar height and the return-to-sport rates also suggested comparable results. Radiographic evaluation demonstrated significantly smaller lateral patellar displacements (P = .004) and bisect offset ratios (P < .001) but similar patellar tilt angles after MPFC-R. Four (5.6%) patients receiving MPFL-R and 2 (3.3%) patients receiving MPFC-R reported recurrence of functional instability, without statistically significant difference. CONCLUSIONS: MPFC-R resulted in similar overall clinical and radiographic outcomes to MPFL-R in treating recurrent patellar dislocation. MPFC-R might not provide additional benefits for patients with an Insall-Salvati index >1.2. LEVEL OF EVIDENCE: Level IV, therapeutic, retrospective cohort study.

Effects of stevia extract on production performance, serum biochemistry, antioxidant capacity, and gut health of laying hens.

In the present study, we aimed to elucidate the effects of stevia extract on production performance, serum immune indexes, intestinal structure, and cecum microbial structure. We randomly divided eight hundred 46-wk-old Roman hens into 5 groups, with 8 replicates in each group and 20 chickens in each replicate. The control group was fed a basal diet, whereas the 4 experimental groups were fed 50, 100, 200, and 400 mg/kg stevia extracts. The study period was 24 wk. The addition of different concentrations of the stevia extract to the diet resulted in significant secondary changes in the egg production rate at 1 to 12 wk (P < 0.05). Furthermore, the addition of 50 and 100 mg/kg stevia extract to the diet significantly increased serum IgM and IgG levels in laying hens (P < 0.05) but linearly decreased serum IL-1ß levels (P < 0.05). Serum T-SOD activity linearly increased (P = 0.057); however, serum biochemical indexes showed no significant differences. Stevia extract tended to increase the ratio of the duodenal villi height to the depth of the crypt (P = 0.067), with no obvious lesions in the duodenum, jejunum, and ileum. In addition, stevia extract increased the relative abundance of species at the phylum level, with the abundance of Bacteroides and Firmicutes exhibiting significant secondary changes (P < 0.05). The ACE and Chao1 indexes suggested that stevia extract addition significantly increased the alpha diversity of cecum microorganisms in laying hens. Furthermore, NMDS analysis based on operational taxonomic units revealed that stevia extract addition increased the beta diversity of cecum microorganisms in laying hens. Adding a certain amount of stevia extract to feed can improve the production performance, immune ability, and intestinal health of laying hens to some extent, and we recommend an effective level of 200mg/kg of stevia extract for laying hen diets.

The Distal Fascicle of the Anterior Inferior Tibiofibular Ligament: A Potential Landmark for Lateral Ankle Ligament Reconstruction.

BACKGROUND: A reliable landmark and precise distances from the ligament attachments are needed for lateral ankle stabilization surgery. The distal fascicle of the anterior inferior tibiofibular ligament (AITFL) has been used to locate the anterior talofibular ligament (ATFL) or calcaneofibular ligament (CFL) centers on the fibula. However, there is no anatomic study to validate the distal fascicle of the AITFL as a landmark of lateral ankle ligament stabilization, and more importantly, the exact distances from the ATFL or CFL attachments to the distal fascicle of the AITFL are unknown. METHODS: Sixteen frozen cadaveric specimens (8 paired specimens) with no previous history of ankle injury were used in this study. Whether the distal fascicle of AITFL was present in each specimen was confirmed. Then, the distances from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL and CFL on the fibula were measured. All measurements were performed by 2 observers, and the intraobserver and interobserver reliabilities were analyzed by intraclass correlation coefficients (ICCs). RESULTS: The distal fascicle of the AITFL was found in all specimens (100%). The mean distance from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL, CFL, and the intersection center of the 2 ligaments on the fibula was 6.0 to 7.1 mm, 11.5 to 13.2 mm, and 9.0 to 10.0 mm, respectively. Excellent interobserver and intraobserver agreement (all ICCs > 0.9, P < .01) was shown in the anatomic measurements of these distances. CONCLUSION: In this cadaveric study, we found that the distal fascicle was a constant structure of the AITFL in the lateral ankle. The distances from the most distal insertion of the AITFL's distal fascicle to the ligamentous footprint centers were reliable and may be used to identify the origins of the ATFL and CFL for lateral ankle ligament reconstruction. CLINICAL RELEVANCE: This anatomic study validates the AITFL's distal fascicle as a potential landmark and, more importantly, determines the range of distances from AITFL's distal fascicle to the attachment centers of lateral ankle ligaments by anatomic measurements. The data may be used to identify the ATFL and CFL for lateral ankle stabilization surgery and become particularly valuable for endoscopic or arthroscopic techniques.

Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks.

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid ß-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Progress in the treatment of malignant ascites.

Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.