Comparative analysis of the femoral neck system (FNS) vs. cannulated cancellous screws (CCS) in the treatment of Middle-aged and elderly patients with femoral neck fractures: clinical outcomes and biomechanical insights.

PURPOSE: This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. METHODS: This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. RESULTS: The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p < 0.05). Harris and VAS scores were higher in the FNS group than in the CCS group (p < 0.05). Postoperative changes in the neck shaft angle and femoral neck shortening were significantly lower in the FNS group than in the CCS group (p < 0.05). The results of the finite element analysis indicated that the maximum stress on the femoral head and varus angle were generally lower in the FNS group than in the CCS group and that the maximum displacement of the femoral head and FNS was generally lower in the FNS group than in the CCS group. However, the superiority of FNS over CCS decreased with increasing Pauwels angle. Additionally, the effectiveness of FNS in limiting displacement of the femoral neck upper wall was not as favourable as that of CCS. CONCLUSIONS: The treatment of femoral neck fractures with FNS is superior and contributes to improved hip joint function. Biomechanical research has confirmed its structural stability and advantages in resisting femoral head varus. However, challenges to its fixation efficacy persist, particularly at higher Pauwels angles.

Establishment and validation of a nomogram model containing a triglyceride-glucose index and neutrophil-to-high-density lipoprotein ratio for predicting major adverse cardiac events in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: To analyze the predictive value of the triglyceride-glucose (TyG) index and neutrophil-to-high-density lipoprotein ratio (NHR) for in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI), and to establish an associated nomogram model. METHODS: In this retrospective study, we collected data from consecutive STEMI patients who underwent PCI from October 2019 to June 2023 at the Second People's Hospital of Hefei and the Second Affiliated Hospital of Anhui Medical University, as training and validation sets. Stepwise regression and multivariate logistic regression analysis were performed to screen independent risk factors, and a nomogram model was constructed and evaluated for its predictive efficacy. RESULTS: The TyG index, NHR, urea, diastolic blood pressure, hypertension, and left ventricular ejection fraction were independent risk factors for in-hospital MACE after PCI, and were used to construct the nomogram model. The C-index of the training and validation sets were 0.799 and 0.753, respectively, suggesting that the model discriminated well. Calibration and clinical decision curves also demonstrated that the nomogram model had good predictive power. CONCLUSION: In STEMI patients, increased TyG index and NHR were closely related to the occurrence of in-hospital MACE after PCI. Our constructed nomogram model has some value for predicting the occurrence of in-hospital MACE in STEMI patients.

Gas6/Axl signaling promotes hematoma resolution and motivates protective microglial responses after intracerebral hemorrhage in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) stands out as the most fatal subtype of stroke, currently devoid of effective therapy. Recent research underscores the significance of Axl and its ligand growth arrest-specific 6 (Gas6) in normal brain function and a spectrum of neurological disorders, including ICH. This study is designed to delve into the role of Gas6/Axl signaling in facilitating hematoma clearance and neuroinflammation resolution following ICH. METHODS: Adult male C57BL/6 mice were randomly assigned to sham and ICH groups. ICH was induced by intrastriatal injection of autologous arterial blood. Recombinant mouse Gas6 (rmGas6) was administered intracerebroventricularly 30 min after ICH. Virus-induced knockdown of Axl or R428 (a selective inhibitor of Axl) treatment was administrated before ICH induction to investigate the protective mechanisms. Molecular changes were assessed using western blot, enzyme-linked immunosorbent assay and immunohistochemistry. Coronal brain slices, brain water content and neurobehavioral tests were employed to evaluate histological and neurofunctional outcomes, respectively. Primary glia cultures and erythrophagocytosis assays were applied for mechanistic studies. RESULTS: The expression of Axl increased at 12 h after ICH, peaking on day 3. Gas6 expression did not remarkably changed until day 3 post-ICH. Early administration of rmGas6 following ICH significantly reduced hematoma volume, mitigated brain edema, and restored neurological function. Both Axl-knockdown and Axl inhibitor treatment abolished the neuroprotection of exogenous Gas6 in ICH. In vitro studies demonstrated that microglia exhibited higher capacity for phagocytosing eryptotic erythrocytes compared to normal erythrocytes, a process reversed by blocking the externalized phosphatidylserine on eryptotic erythrocytes. The erythrophagocytosis by microglia was Axl-mediated and Gas6-dependent. Augmentation of Gas6/Axl signaling attenuated neuroinflammation and drove microglia towards pro-resolving phenotype. CONCLUSIONS: This study demonstrated the beneficial effects of recombinant Gas6 on hematoma resolution, alleviation of neuroinflammation, and neurofunctional recovery in an animal model of ICH. These effects were primarily mediated by the phagocytotic role of Axl expressed on microglia.

"A diamond-shaped" penoplasty technique with or without concurrent suprapubic liposuction for adult-acquired buried penis: clinical outcomes and patient satisfaction rates.

Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes.

BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.

Accurately identifying positive and negative regulation of apoptosis using fusion features and machine learning methods.

Apoptotic proteins play a crucial role in the apoptosis process, ensuring a balance between cell proliferation and death. Thus, further elucidating the regulatory mechanisms of apoptosis will enhance our understanding of their functions. However, the development of computational methods to accurately identify positive and negative regulation of apoptosis remains a significant challenge. This work proposes a machine learning model based on multi-feature fusion to effectively identify the roles of positive and negative regulation of apoptosis. Initially, we constructed a reliable benchmark dataset containing 200 positive regulation of apoptosis and 241 negative regulation of apoptosis proteins. Subsequently, we developed a classifier that combines the support vector machine (SVM) with pseudo composition of k-spaced amino acid pairs (PseCKSAAP), composition transition distribution (CTD), dipeptide deviation from expected mean (DDE), and PSSM-composition to identify these proteins. Analysis of variance (ANOVA) was employed to select optimized features that could yield the maximum prediction performance. Evaluating the proposed model on independent data revealed and achieved an accuracy of 0.781 with an AUROC of 0.837, demonstrating our model's potent capabilities.

0D-2D multifunctional bimetallic MOF derivative-MXene heterojunction for high areal capacity lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries have attracted much attention due to their high specific capacity. However, at high loads and rates, the polysulfides conversion rate and ion transport of batteries are slow, limiting their commercialization. This work reports zero-dimensional (0D) bimetallic MOF derivatives grown in situ on two-dimensional (2D) MXene by electrostatic adsorption (FeCo@Ti3C2). The 0D bimetallic structure effectively avoids the stacking of MXene while providing a dual catalytic site for polysulfides. The 2D structure of MXene also provides a large number of pathways for the rapid diffusion of lithium ions. This 0D-2D heterostructured heterogeneous catalyst with bimetallic synergistic active sites efficiently immobilizes and catalyzes polysulfides, providing a fast charge transfer pathway for the electrochemical reaction of lithium polysulfides. The Li-S battery with this multifunctional 0D-2D heterojunction structure catalyst has outstanding high rate capacity (703 mAh g-1 at 4 C at room temperature and 555 mAh g-1 at 2 C at 0 °C), fascinating capacity at high load (5.5 mAh cm-2 after 100 cycles at a high sulfur content of 8.2 mg cm-2). The study provides new ideas for the commercialization of high-efficiency Li-S batteries.

Soil microbial community composition and nitrogen enrichment responses to the operation of electric power substation.

The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.

Non-pyrolytic synthesis of laccase-like iron based single-atom nanozymes for highly efficient dual-mode colorimetric and fluorescence detection of epinephrine.

Single-atom nanozymes have garnered significant attention due to their exceptional atom utilization and ability to establish well-defined structure-activity relationships. However, conventional pyrolytic synthesis methods pose challenges such as high energy consumption and random local environments at the active sites, while achieving non-pyrolytic synthesis of single-atom nanozymes remains a formidable technical hurdle. The present study focuses on the synthesis of laccase-like iron-based single-atom nanozymes (Fe-SAzymes) using a non-pyrolysis method facilitated by microwave irradiation. Under low iron loading conditions, Fe-SAzymes exhibited significantly enhanced laccase activity (12.1 U/mg), surpassing that of laccase by 24-fold. Moreover, Fe-SAzymes demonstrated efficient catalytic oxidation of epinephrine (EP), enabling its colorimetric detection. Owing to the remarkable laccase activity of Fe-SAzymes, the conventional nanozymes EP detection time was reduced from 60 min to 20 min, with an impressive low detection limit as low as 2.95 µM. In addition, an ultra-sensitive fluorescence method for EP detection was developed using the internal filter effect of EP oxidation products and CDs combined with carbon dots probe. The detection limit of fluorescence method was only 0.39 µM. Therefore, an visual, fast, and highly sensitive dual-mode EP detection strategy has great potential in the clinical diagnostic industry.

Hydroxyl-Amide Alkaloids from Pepper Roots: Potential Sources of Natural Antioxidants and Tyrosinase Inhibitors.

Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.

Identification of Coupled Landau and Anomalous Resonances in Space Plasmas.

Wave-particle resonance, a ubiquitous process in the plasma universe, occurs when resonant particles observe a constant wave phase to enable sustained energy transfer. Here, we present spacecraft observations of simultaneous Landau and anomalous resonances between oblique whistler waves and the same group of protons, which are evidenced, respectively, by phase-space rings in parallel-velocity spectra and phase-bunched distributions in gyrophase spectra. Our results indicate the coupling between Landau and anomalous resonances via the overlapping of the resonance islands.

Based on machine learning, CDC20 has been identified as a biomarker for postoperative recurrence and progression in stage I & II lung adenocarcinoma patients.

Objective: By utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets. Methods: To begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment. Results: First, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway. Conclusion: CDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.

Impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients: a propensity score-matched retrospective study.

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.

Adipose stem cell-derived exosomes in the treatment of wound healing in preclinical animal models: a meta-analysis.

Background: Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation. Methods: A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses. Results: The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91-3.83)] and day 14 (SMD 2.89, 95%CI 1.47-4.30). Day 14 (SMD 3.43, 95%CI 1.28-5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos. Conclusions: A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.

Generating high purity and yield of capsanthin and capsorubin carrot germplasm through synthetic metabolic engineering.

Capsanthin and capsorubin are red κ-xanthophylls exclusively found in a handful of other plant species. Currently, capsanthin and capsorubin are only extracted from red pepper. Here, high purity production of capsanthin and capsorubin has been achieved in carrot taproot by synthetic metabolic engineering strategy. Expression of a capsanthin-capsorubin synthase gene (CaCCS) from pepper resulted in dominant production of capsanthin whereas expression of a LiCCS gene from tiger lily resulted in production of both capsanthin and capsorubin in carrot taproot. The highest content of capsanthin and capsorubin was obtained in LiC-1 carrot taproot hosting the LiCCS gene, 150.09 µg/g DW (dry weight). Co-expression of DcBCH1 with CCS could improve the purity of capsanthin and capsorubin by eliminating the non-target carotenoids (eg. α-carotene and ß-carotene). The highest purity of capsanthin and capsorubin was obtained in BLiC-1 carrot taproot hosting DcBCH1+LiCCS genes, 91.10% of total carotenoids. The non-native pigments were esterified partially and stored in the globular chromoplast of carrot taproot. Our results demonstrated the possibility of employing carrot taproot as green factories for high purity production of capsanthin and capsorubin. The capsanthin/capsorubin carrot germplasms were also valuable materials for breeding colorful carrots cultivars.

Lewis Acid-Driven Multicomponent Reactions Enable 2-Alkyl Chromanones with Anticancer Activities.

2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.

Tailoring Polyamide Nanofiltration Membranes by Switching Charge of Nanocellulose Interlayers.

The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (⊖-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the ⊖-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the ⊖-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the ⊖-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.

Rescue and characterization of PCV4 infectious clones: pathogenesis and immune response in piglets.

Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.

Tracheoplasty should be proactively considered within the surgical strategy for treating the ring-sling complex.

BACKGROUND: To examine the safety and effectiveness of proactive tracheoplasty for pediatric ring-sling complexes. METHODS: We retrospectively collected the data from 304 children who were diagnosed with a ring-sling complex and underwent surgery at three cardiac centers in China between January 2010 and June 2023. Children were categorized into three surgical groups: concurrent sling and tracheal surgery (Group A, n=258), staged sling and tracheal surgery (Group B, n=25), and sling-only surgery (Group C, n=21). We compared perioperative clinical characteristics, tracheal morphology changes, and outcomes across the groups. RESULTS: The median age of the children was 1.2 (IQR: 0.7-1.9) years. The anomalous tracheobronchial arborization rates were higher in Groups A (52.5%) and B (60.0%) than in Group C (15.0%). The preoperative narrow-wide ratio (NWR) was lower in Groups A and B than in Group C, with values of 0.44 (IQR: 0.35-0.52), 0.44 (0.33-0.59), and 0.68 (0.54-0.72), respectively (P<0.001). Preoperative subcarina angles were similar among the groups (P=0.54). After specific surgeries, the NWR and subcarina angle significantly improved in Groups A and B but not in Group C. There were seven in-hospital deaths and two post-discharge deaths. Respiratory symptoms improved in Groups A and B but seven children in Group C remained respiratory dysfunction. Six children presented with residual stenosis of the left pulmonary artery. CONCLUSION: Concurrent sling and tracheal surgeries for children with the ring-sling complex are safe and effective and are especially preferable for those with NWR ≤0.6, long-segment or diffuse tracheal stenosis, anomalous tracheobronchial arborization, and pronounced respiratory symptoms.

The integrated analysis of gut microbiota and metabolome revealed steroid hormone biosynthesis is a critical pathway in liver regeneration after 2/3 partial hepatectomy.

Introduction: The liver is the only organ capable of full regeneration in mammals. However, the exact mechanism of gut microbiota and metabolites derived from them relating to liver regeneration has not been fully elucidated. Methods: To demonstrate how the gut-liver axis contributes to liver regeneration, using an LC-QTOF/MS-based metabolomics technique, we examine the gut microbiota-derived metabolites in the gut content of C57BL/6J mice at various points after 2/3 partial hepatectomy (PHx). Compound identification, multivariate/univariate data analysis and pathway analysis were performed subsequently. The diversity of the bacterial communities in the gastrointestinal content was measured using 16S rRNA gene sequencing. Then, the integration analysis of gut microbiota and metabolome was performed. Results: After 2/3 PHx, the residual liver proliferated quickly in the first 3 days and had about 90% of its initial weight by the seventh day. The results of PLS-DA showed that a significant metabolic shift occurred at 6 h and 36 h after 2/3 PHx that was reversed at the late phase of liver regeneration. The α and ß-diversity of the gut microbiota significantly changed at the early stage of liver regeneration. Specifically, Escherichia Shigella, Lactobacillus, Akkermansia, and Muribaculaceae were the bacteria that changed the most considerably during liver regeneration. Further pathway analysis found the most influenced co-metabolized pathways between the host and gut bacteria including glycolysis, the TCA cycle, arginine metabolism, glutathione metabolism, tryptophan metabolism, and purine and pyrimidine metabolism. Specifically, steroid hormone biosynthesis is the most significant pathway of the host during liver regeneration. Discussion: These findings revealed that during liver regeneration, there was a broad modification of gut microbiota and systemic metabolism and they were strongly correlated. Targeting specific gut bacterial strains, especially increasing the abundance of Akkermansia and decreasing the abundance of Enterobacteriaceae, may be a promising beneficial strategy to modulate systemic metabolism such as amino acid and nucleotide metabolism and promote liver regeneration.