Evaluating three internal fixation techniques for Pauwels III femoral neck fractures via finite element analysis.

The selection of implants for fixing unstable femoral neck fractures (FNF) remains contentious. This study employs finite element analysis to examine the biomechanics of treating Pauwels type III femoral neck fractures using cannulated compression screws (3CS), biplane double-supported screw fixation (BDSF), and the femoral neck system (FNS). A three-dimensional model of the proximal femur was developed using computed tomography scans. Fracture models of the femoral neck were created with 3CS, BDSF, and FNS fixations. Von Mises stress on the proximal femur, fracture ends, internal fixators, and model displacements were assessed and compared across the three fixation methods (3CS, BDSF, and FNS) during the heel strike of normal walking. The maximum Von Mises stress in the proximal fragment was significantly higher with 3CS fixation compared to BDSF and FNS fixations (120.45 MPa vs. 82.44 MPa and 84.54 MPa, respectively). Regarding Von Mises stress distribution at the fracture ends, the highest stress in the 3CS group was 57.32 MPa, while BDSF and FNS groups showed 51.39 MPa and 49.23 MPa, respectively. Concerning implant stress, the FNS model exhibited greater Von Mises stress compared to the 3CS and BDSF models (236.67 MPa vs. 134.86 MPa and 140.69 MPa, respectively). Moreover, BDSF displayed slightly lower total displacement than 3CS fixation (7.19 mm vs. 7.66 mm), but slightly higher displacement than FNS (7.19 mm vs. 7.03 mm). This study concludes that BDSF outperforms 3CS fixation in terms of biomechanical efficacy and demonstrates similar performance to the FNS approach. As a result, BDSF stands as a dependable alternative for treating Pauwels type III femoral neck fractures.

New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant Mycobacterium tuberculosis.

Introduction. Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ.Hypothesis. Sfx is more active against drug-resistant Mycobacterium tuberculosis (Mtb) isolates.Aim. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb.Methods. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes.Results. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC50 of 0.0313 µg ml-1 and MIC90 of 0.125 µg ml-1, which was lower than that of Mfx (MIC50 = 0.0625 µg ml-1, MIC90 = 1 µg ml-1) and Lfx (MIC50 = 0.125 µg ml-1, MIC90 = 2 µg ml-1). We determined the tentative epidemiological cut-off values as 0.5 µg ml-1 for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in gyrA or gyrB, 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident.Conclusion. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.

Urinary cytologic features of primitive neuroectodermal tumor primarily involving the kidney: A case report.

Renal primitive neuroectodermal tumor(rPNET) is an extremely rare and distinct entity that can be mistaken for a variety of other round cell tumors. Findings from fine needle aspiration cytology have been reported, but there have been no reports of PNET cytomorphological features in urine cytology specimen. Here, we report a case of PNET characterized by urine cytology. A 24-year-old girl presented with hematuria for half a month. Computed tomography showed a large tumor involving the upper pole of the right kidney. Urinary cytology exhibited highly cellular clusters composed of small, round, atypical cells with little cytoplasm and a high nuclear/cytoplasmic ratio. Following a right nephrectomy, the biopsy confirmed the diagnosis of rPNET. Additionally, immunohistochemistry (IHC) staining of the decolorized liquid-based cytology slide was positive for CD99, further confirming the diagnosis through urine cytology. Our observations suggest that urinary cytology in combination with cytological morphology and immunocytochemistry may be a potentially useful method for the detection of PNET.

What is the force required to treat trismus in patients undergoing oral cavity free flap reconstruction?

BACKGROUND: Trismus therapy is often delayed after jaw reconstruction to avoid hardware failure or non-union. The aim of this study is to document the forces that have been applied to patients undergoing free flap reconstruction of the oral cavity in the 12 months following oral cavity reconstruction, and to analyze the associations between force and maximal interincisal opening (MIO) over time. METHODS: Participants with trismus after free flap reconstruction of the oral cavity completed a 10-week jaw stretching program using Restorabite™. Primary outcome measures included the minimum and maximal force applied by a trismus device during rehabilitation, MIO, bone union, and health-related quality of life outcomes up to 12 months postoperatively. RESULTS: A mean of 20.6 Newtons (N) was used during passive exercises and 38.9 N during active exercises was used during trismus therapy. The mean increase in MIO for the 45 participants after 10 weeks, 6 months, and 12 months of therapy was 8.4 mm (p < 0.001), 12.6 mm (p < 0.001), 12.7 mm (p < 0.001), respectively. There was no significant difference in the mean minimal (p = 0.37) or mean maximal (p = 0.08) force applied between those who underwent osseous free flap reconstruction compared to fasciocutaneous only, respectively. In patients who underwent osseous reconstruction, 25 (67.6%) had complete bone union and 12 (32.4%) had partial union at 12 months postsurgery. CONCLUSIONS: In participants undergoing osseous free flap reconstruction, there was no association between the force applied to the rates of bone union. Further research to define safe and optimal loading may benefit patients undergoing jaw reconstruction.

Is Bigger Better? Comparison of 150 µm and 200 µm Thulium Fiber for In Situ Lower-Pole Lithotripsy.

Introduction: The thulium fiber laser (TFL) generates a focused beam, which can be transmitted to laser fibers with small core diameters and may facilitate in situ lower-pole lithotripsy. This study compares lithotripsy performance of the 150 and 200 µm TFL in a lower pole benchtop kidney model. Materials and Methods: Using a 3D model printed from an actual kidney, in situ laser lithotripsy was performed on 1 cm lower-pole BegoStones (calcium oxalate monohydrate consistency) using four different settings (all 20W) and two fiber sizes (150 and 200 µm). Procedure time, laser time, total pulse energy, and fiber stripping were compared between the two fibers using an ANOVA or independent t-test. Results: The 150 µm fiber at 0.2 J × 100 Hz had the shortest lasing and procedure time (17.3 and 18.5 minutes) and lowest total pulse energy (20.75 kJ) compared with other study arms (p < 0.001). Overall procedure time, lasing time, and total pulse energy were significantly different between the 8 settings (p < 0.001 for all). At higher frequency (100 and 200 Hz), lasing time was significantly faster compared with 20 and 50 Hz (19.9 vs 27.3 minutes; p < 0.001). Furthermore, the average total procedure time was shorter with 150 µm compared with 200 µm regardless of settings (23.2 vs 29.8 minutes; p < 0.001). Conclusion: The 150 µm fiber results in shorter procedure and lasing time at lower total energy levels during lower-pole in situ lithotripsy. Overall, the fastest setting was 0.2 J and 100 Hz with the 150 µm fiber. Smaller laser fibers can potentially allow more efficient in situ laser lithotripsy with better irrigation and visibility at higher deflection angles.

Efficacy and safety of regorafenib as a first-line agent alone or in combination with an immune checkpoint inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study.

Background: The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC. Methods: We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records. Results: Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively. Conclusions: Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study.

Molecular Insights into Soaking in Hybrid N2-CO2 Huff-n-Puff: A Case Study of a Single Quartz Nanopore-Hydrocarbon System.

Hybrid N2-CO2 huff-n-puff (HnP) has been experimentally demonstrated to be a promising approach for improving oil recovery from tight/ultratight shale oil reservoirs. Despite this, the detailed soaking process and interaction mechanisms remain unclear. Adopting molecular dynamic simulations, the soaking behavior of hybrid N2-CO2 HnP was investigated at the molecular and atomic levels. Initially, the soaking process of fluid pressure equilibrium after injection pressure decays in a single matrix nanopore connected to a shale oil reservoir is studied. The study revealed that counter-current and cocurrent displacement processes exist during the CO2 and hybrid N2-CO2 soaking, but cocurrent displacement occurs much later than counter-current displacement. Although the total displacement efficiency of the hybrid N2-CO2 soaking system is lower than that of the CO2 soaking system, the cocurrent displacement initiates earlier in the hybrid N2-CO2 soaking system than in the CO2 soaking system. Moreover, the N2 soaking process is characterized by only counter-current displacement. Next, the soaking process of fluid pressure nonequilibrium before the injection pressure decays is investigated. It was discovered that counter-current and cocurrent displacement processes initiate simultaneously during the CO2, N2, and hybrid N2-CO2 soaking process, but cocurrent displacement exerts a dominant influence. During the CO2 soaking process, many hydrocarbon molecules in the nanopore are dissolved in CO2 while simultaneously exhibiting a substantial retention effect in the nanopore. After pure N2 injection, there is a tendency to form a favorable path of N2 through the oil phase. The injection of hybrid CO2-N2 facilitates the most significant cocurrent displacement effect and the reduction in residual oil retained in the nanopore during the soaking process, thus resulting in the best oil recovery. However, the increase rate in total displacement efficiencies of the different soaking systems over time (especially the hybrid N2-CO2 soaking system) was significantly larger before than after injection pressure decays. Additionally, the displacement effect induced by oil volume swelling is significantly restricted before the injection pressure decays compared to the soaking process after the injection pressure decays. This study explains the role of CO2-induced oil swelling and N2-induced elastic energy played by hybrid N2 and CO2 at different stages of the hybrid N2-CO2 soaking process before and after pressure decays and provides theoretical insights for hybrid gas HnP-enhanced recovery. These pore-scale results highlight the importance of injection pressure and medium composition during the soaking process in unconventional oil reservoirs.

CO2-Controlled Water Injection in Carbonate Gas Reservoirs: An Effective Approach to Improve Production.

In the development of edgewater-type carbonate gas reservoirs, the challenge posed by water flooding in production wells is a significant concern. This study investigates the potential of CO2 injection as a solution for water control. Experiments were conducted to understand the gas-water flow dynamics during CO2-controlled water injection in a series-connected core. Emphasis was placed on the effects of varying the CO2 injection pressure on water flow and gas cumulative production rate. The mechanisms influencing water control and production efficiency across different injection pressures in multiwell production were elucidated. The results showed that the gas production rate of the core increased by 27.2% over the depletion production rate after the CO2 injection pressure was increased from 8 to 13 MPa. The gas production rate increases during the second development cycle from 20% to 55% after switching to CO2 injection, which pushes the edge water further back, slowing down side water flow in the core in the form of segmental plugs, and prolonging the time before water breakthrough. The production time and water breakthrough time for the second development cycle increased with increasing CO2 injection, while the degree of water flow on the core side decreased. These insights are crucial for optimizing the recovery efficiency of edgewater-type gas reservoirs and provide guidance on the application of CO2 injection for water control and CO2 sequestration in carbonate gas reservoirs.

Computer-aided design and 3D printing for a stable construction of segmental bone defect model in Beagles: a short term observation.

OBJECTIVE: Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode. METHODS: CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively. RESULTS: In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23-68 min) to 26 ± 4.6 (19-36 min) (n = 10, p < 0.05) and the accuracy of intramedullary fixation placement increased from 71.6 ± 23.6 (33.3-100) % to 98.3 ± 5.37 (83-100) %, (n = 30, p < 0.05) with the use of CAD and 3D printed instruments. All Beagles were load-bearing within 1 week, and postoperative radiographs showed no evidence of implant failure. CONCLUSION: Incorporation of CAD and 3D printing significantly increases stability, while reducing the surgical time in the construction of the animal model, significantly affecting the success of the segmental bone defect model in Beagles.

Double Trouble: A Case Report of Caudal Duplication Syndrome.

Caudal duplication syndrome is a rare congenital anomaly with various duplications of structures derived from the embryonic cloaca and notochord. A male neonate was born with diphallia, bifid scrotum and duplicated anorectal malformation. Diagnostic and operative evaluation identified a partially duplicated right kidney with left-to-right crossed fused ectopia, bilateral hydronephrosis, two separate hemi-bladders, left ectopic ureter with vesicoureteral reflux, and a left rectourethral fistula. To our knowledge, this is the first reported caudal duplication anomaly with complete genitourinary duplication, with diphallia, duplicated bladder, bifid scrotum, extra-numerary kidneys and a duplicated rectum.

Utilizing Deep Learning for Defect Inspection in Hand Tool Assembly.

The integrity of product assembly in the precision assembly industry significantly influences the quality of the final products. During the assembly process, products may acquire assembly defects due to personnel oversight. A severe assembly defect could impair the product's normal function and potentially cause loss of life or property for the user. For workpiece defect inspection, there is limited discussion on the simultaneous detection of the primary kinds of assembly anomaly (missing parts, misplaced parts, foreign objects, and extra parts). However, these assembly anomalies account for most customer complaints in the traditional hand tool industry. This is because no equipment can comprehensively inspect major assembly defects, and inspections rely solely on professionals using simple tools and their own experience. Thus, this study proposes an automated visual inspection system to achieve defect inspection in hand tool assembly. This study samples the work-in-process from three assembly stations in the ratchet wrench assembly process; an investigation of 28 common assembly defect types is presented, covering the 4 kinds of assembly anomaly in the assembly operation; also, this study captures sample images of various assembly defects for the experiments. First, the captured images are filtered to eliminate surface reflection noise from the workpiece; then, a circular mask is given at the assembly position to extract the ROI area; next, the filtered ROI images are used to create a defect-type label set using manual annotation; after this, the R-CNN series network models are applied to object feature extraction and classification; finally, they are compared with other object detection models to identify which inspection model has the better performance. The experimental results show that, if each station uses the best model for defect inspection, it can effectively detect and classify defects. The average defect detection rate (1-ß) of each station is 92.64%, the average misjudgment rate (α) is 6.68%, and the average correct classification rate (CR) is 88.03%.

Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling.

BACKGROUND: Astragaloside IV (AST-IV), as an effective active ingredient of Astragalus membranaceus (Fisch.) Bunge. It has been found that AST-IV inhibits the replication of dengue virus, hepatitis B virus, adenovirus, and coxsackievirus B3. Enterovirus 71 (EV71) serves as the main pathogen in severe hand-foot-mouth disease (HFMD), but there are no specific drugs available. In this study, we focus on investigating whether AST-IV can inhibit EV71 replication and explore the potential underlying mechanisms. METHODS: The GES-1 or RD cells were infected with EV71, treated with AST-IV, or co-treated with both EV71 and AST-IV. The EV71 structural protein VP1 levels, the viral titers in the supernatant were measured using western blot and 50% tissue culture infective dose (TCID50), respectively. Network pharmacology was used to predict possible pathways and targets for AST-IV to inhibit EV71 replication. Additionally, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to investigate the potential targeted metabolites of AST-IV. Associations between metabolites and apparent indicators were performed via Spearman's algorithm. RESULTS: This study illustrated that AST-IV effectively inhibited EV71 replication. Network pharmacology suggested that AST-IV inhibits EV71 replication by targeting PI3K-AKT. Metabolomics results showed that AST-IV achieved these effects by elevating the levels of hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-hydroxy-1 H-indole-3- acetamide, oxypurinol, while reducing the levels of PC (14:0/15:0). Furthermore, AST-IV also mitigated EV71-induced oxidative stress by reducing the levels of MDA, ROS, while increasing the activity of T-AOC, CAT, GSH-Px. The inhibition of EV71 replication was also observed when using the ROS inhibitor N-Acetylcysteine (NAC). Additionally, AST-IV exhibited the ability to activate the PI3K-AKT signaling pathway and suppress EV71-induced apoptosis. CONCLUSION: This study suggests that AST-IV may activate the cAMP and the antioxidant stress response by targeting eight key metabolites, including hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-Hydroxy-1 H-indole-3-acetamide, oxypurinol and PC (14:0/15:0). This activation can further stimulate the PI3K-AKT signaling to inhibit EV71-induced apoptosis and EV71 replication.

Real-World Assessment of Recommended COVID-19 Vaccination Waiting Period after Chemotherapy.

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan-Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035-1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083-2.014), and sepsis (HR: 1.854, 95% CI: 1.091-3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354-2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine.

Nationwide Big Data Analysis of Statin Use and Intracerebral Hemorrhage Risk in Acute Ischemic Stroke Patients in Taiwan.

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.

Climate sensitivity and relative humidity changes in global storm-resolving model simulations of climate change.

The climate simulation frontier of a global storm-resolving model (GSRM; or k-scale model because of its kilometer-scale horizontal resolution) is deployed for climate change simulations. The climate sensitivity, effective radiative forcing, and relative humidity changes are assessed in multiyear atmospheric GSRM simulations with perturbed sea-surface temperatures and/or carbon dioxide concentrations. Our comparisons to conventional climate model results can build confidence in the existing climate models or highlight important areas for additional research. This GSRM's climate sensitivity is within the range of conventional climate models, although on the lower end as the result of neutral, rather than amplifying, shortwave feedbacks. Its radiative forcing from carbon dioxide is higher than conventional climate models, and this arises from a bias in climatological clouds and an explicitly simulated high-cloud adjustment. Last, the pattern and magnitude of relative humidity changes, simulated with greater fidelity via explicitly resolving convection, are notably similar to conventional climate models.

Impact of traumatic brain injury on risk for schizophrenia and bipolar disorder.

The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.

Ultrasound-targeted microbubble destruction facilitates cartilage repair through increased the migration of mesenchymal stem cells via HIF-1α-mediated glycolysis pathway in rats.

OBJECTIVE: Mesenchymal stem cells (MSCs) can treat osteoarthritis (OA), but their therapeutic efficacy is poor to date due to low migration efficiency. This study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) could ameliorate cartilage repair efficiency through facilitating the migration of MSCs via hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis regulatory pathway in OA model rats. METHODS: OA rats were treated with MSCs alone or in combination with UTMD, respectively, for 4 weeks. Cartilage histopathology, MSCs migration efficiency, von Frey fiber thresholds, and the expression levels of collagen II and MMP-13 were measured. Further, MSCs were extracted from the bone marrow of rats, cocultured with osteoarthritic chondrocytes, transfected to siRNA-HIF-1α, and subjected to UTMD for 4 days. Glucose consumption, lactate production, and cell migration efficiency were assessed. The protein expression levels of HIF-1α, HK2, PKM2, and GLUT1 were measured, respectively. RESULTS: In OA rat model, NC-MSCs + UTMD improved migration efficiency, increased collagen II expression, decreased MMP-13 expression, and delayed osteoarthritis progression. Silencing HIF-1α attenuated the effects induced by UTMD. In vitro, UTMD led to increases in MSC activity and migration, glucose consumption, lactate production, and the protein expression of HIF-1α, HK2, PKM2, and GLUT1 expression, all of which were reversed upon HIF-1α silencing. CONCLUSION: UTMD enhances MSCs migration and improves cartilage repair efficiency through the HIF-1α-mediated glycolytic regulatory pathway, providing a novel therapy strategy for knee osteoarthritis.

A complementary metaproteomic approach to interrogate microbiome cultivated from clinical colon biopsies.

The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic and functional analyses with Unipept Desktop and MetaLab-MAG. Across seven samples, we identified and matched nearly 36,000 unique peptides to approximately 300 species and 11 phyla. Unipept Desktop provided gene ontology, InterPro entries, and enzyme commission number annotations, facilitating the identification of relevant metabolic pathways. MetaLab-MAG contributed functional annotations through Clusters of Orthologous Genes and Non-supervised Orthologous Groups categories. These results unveiled functional similarities and differences among the samples. This integrated pipeline holds the potential to provide deeper insights into the taxonomy and functions of the human gut microbiome for interrogating the intricate connections between microbiome balance and diseases.