Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment.

Collagen fibers in the 3D tumor microenvironment (TME) exhibit complex alignment landscapes that are critical in directing cell migration through a process called contact guidance. Previous in vitro work studying this phenomenon has focused on quantifying cell responses in uniformly aligned environments. However, the TME also features short-range gradients in fiber alignment that result from cell-induced traction forces. Although the influence of graded biophysical taxis cues is well established, cell responses to physiological alignment gradients remain largely unexplored. In this work, fiber alignment gradients in biopsy samples are characterized and recreated using a new microfluidic biofabrication technique to achieve tunable sub-millimeter to millimeter scale gradients. This study represents the first successful engineering of continuous alignment gradients in soft, natural biomaterials. Migration experiments on graded alignment show that HUVECs exhibit increased directionality, persistence, and speed compared to uniform and unaligned fiber architectures. Similarly, patterned MDA-MB-231 aggregates exhibit biased migration toward increasing fiber alignment, suggesting a role for alignment gradients as a taxis cue. This user-friendly approach, requiring no specialized equipment, is anticipated to offer new insights into the biophysical cues that cells interpret as they traverse the extracellular matrix, with broad applicability in healthy and diseased tissue environments.

Chemistry Aspects and Designing Strategies of Flexible Materials for High-Performance Flexible Lithium-Ion Batteries.

In recent years, flexible and wearable electronics such as smart cards, smart fabrics, bio-sensors, soft robotics, and internet-linked electronics have impacted our lives. In order to meet the requirements of more flexible and adaptable paradigm shifts, wearable products may need to be seamlessly integrated. A great deal of effort has been made in the last two decades to develop flexible lithium-ion batteries (FLIBs). The selection of suitable flexible materials is important for the development of flexible electrolytes self-supported and supported electrodes. This review is focused on the critical discussion of the factors that evaluate the flexibility of the materials and their potential path toward achieving the FLIBs. Following this analysis, we present how to evaluate the flexibility of the battery materials and FLIBs. We describe the chemistry of carbon-based materials, covalent-organic frameworks (COFs), metal-organic frameworks (MOFs), and MXene-based materials and their flexible cell design that represented excellent electrochemical performances during bending. Furthermore, the application of state-of-the-art solid polymer and solid electrolytes to accelerate the development of FLIBs is introduced. Analyzing the contributions and developments of different countries has also been highlighted in the past decade. In addition, the prospects and potential of flexible materials and their engineering are also discussed, providing the roadmap for further developments in this fast-evolving field of FLIB research.

Yolk-shell Co3 O4 @Fe3 O4 /C Nanocomposites as a Heterogeneous Fenton-like Catalyst for Organic Dye Removal.

The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites with Co3 O4 as the core, Fe3 O4 /C as the shell, and a cavity structure were synthesized by the hard template method. The physical and chemical properties of the composites were characterized by SEM, TEM, XRD, TGA, XPS, BET, and VSM. The specific surface area of yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites is 175.9 m2  g-1 , showing superparamagnetic properties. The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites were used as heterogeneous Fenton catalysts to activate peroxymonosulfate (PMS) to degrade MB, which showed high catalytic degradation performance. The degradation rate of MB reached 100 % within 30 min under the circumstances of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites dosage of 0.1 g L-1 , the PMS dosage of 1.0 g L-1 , the initial MB concentration of 100 mg L-1 , an initial pH of 5.5, and a temperature of 30±2 °C. The enhanced catalytic performance of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be attributed to the synergistic effect of the two catalytically active materials and the middle cavity. The effects of different operating parameters and co-existing anion species on MB degradation were also investigated. Electron paramagnetic resonance (EPR) analysis and quenching experiments confirmed that the formation of SO4 ⋅- in the yolk-shell Co3 O4 @Fe3 O4 /C/PMS system contributes to MB degradation. In addition, yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be easily separated from the pollutant solution under the action of an external magnetic field, and the degradation rate of MB can still reach 98 % after five cycles, indicating that it has good stability and reusability and has broad application prospects in the field of water purification.

BBSF: Blockchain-Based Secure Weather Forecasting Information through Routing Protocol in Vanet.

A vehicular ad hoc network (VANET) is a technique that uses vehicles with the ability to sense data from the environment and use it for their safety measures. Flooding is a commonly used term used for sending network packets. VANET may cause redundancy, delay, collision, and the incorrect receipt of the messages to their destination. Weather information is one of the most important types of information used for network control and provides an enhanced version of the network simulation environments. The network traffic delay and packet losses are the main problems identified inside the network. In this research, we propose a routing protocol which can transmit the weather forecasting information on demand based on source vehicle to destination vehicles, with the minimum number of hop counts, and provide significant control over network performance parameters. We propose a BBSF-based routing approach. The proposed technique effectively enhances the routing information and provides the secure and reliable service delivery of the network performance. The results taken from the network are based on hop count, network latency, network overhead, and packet delivery ratio. The results effectively show that the proposed technique is reliable in reducing the network latency, and that the hop count is minimized when transferring the weather information.

Modeling of Efficient Control Strategies for LCC-HVDC Systems: A Case Study of Matiari-Lahore HVDC Power Transmission Line.

With the recent development in power electronic devices, HVDC (High Voltage Direct Current) systems have been recognized as the most prominent solution to transmit electric power economically. Today, several HVDC projects have been implemented physically. The conventional HVDC systems use grid commutation converters, and its commutation relies on an AC system for the provision of voltage. Due to this reason, there are possibilities of commutation failure during fault. Furthermore, once the DC (Direct Current) system power is interrupted momentarily, the reversal of work power is likely to cause transient over-voltage, which will endanger the safety of power grid operation. Hence, it is necessary to study the commutation failure and transient over-voltage issues. To tackle the above issues, in this paper, the dynamic and transient characteristics of Pakistan's first HVDC project, i.e., the Matiari-Lahore ±660 kV transmission line has been analyzed in an electromagnetic transient model of PSCAD/EMTDC. Based on the characteristics of the DC and the off-angle after the failure, a new control strategy has been proposed. The HVDC system along with its proposed control strategy has been tested under various operating conditions. The proposed controller increases the speed of fault detection, reduces the drop of AC voltage and DC and suppresses the commutation failure probability of LCC-HVDC (line commutated converter- high voltage direct current).

Engineering fiber anisotropy within natural collagen hydrogels.

It is well known that biophysical properties of the extracellular matrix (ECM), including stiffness, porosity, composition, and fiber alignment (anisotropy), play a crucial role in controlling cell behavior in vivo. Type I collagen (collagen I) is a ubiquitous structural component in the ECM and has become a popular hydrogel material that can be tuned to replicate the mechanical properties found in vivo. In this review article, we describe popular methods to create 2-D and 3-D collagen I hydrogels with anisotropic fiber architectures. We focus on methods that can be readily translated from engineering and materials science laboratories to the life-science community with the overall goal of helping to increase the physiological relevance of cell culture assays.

Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study.

OBJECTIVE: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. METHODS: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. RESULTS: Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15-60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. CONCLUSION: Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.

Investigating structure-charge transport relationships in thiophene substituted naphthyridine crystalline materials by computational model systems.

The development of novel π-conjugated charge transfer mediators is at the forefront of current research efforts and interests. Among the plethora of building blocks, diketopyrrolopyrroles have been widely employed, associated to the ease of tailoring their optoelectronic properties by systematic peripheral substitutions. It is somehow of surprise to us that their six-member ring bis-lactam analogues, naphthyridines have been overlooked and reports are scarce and almost solely limited to their use in polymeric materials. Herein we report a comprehensive theoretical analysis of the charge transfer properties of 1,5-naphthyridine-based materials by means of a number of bespoke model systems, further able to quantitatively predict experimental mobility observations. Our results imply that thiophene substituted naphthyridine crystalline materials represent a promising class of organic π-conjugated systems with an experimentally observed ability to self-assemble in the solid state conforming to one dimensional stacking motifs. These highly sought-after charge propagation channels are characterised by large wavefunction overlap and thermal integrity and have as a result the potential to outperform currently exploited alternatives. We anticipate this work to be of interest to materials scientists and hope it will pave the way towards the realisation of novel charge transfer mediators exploiting naphthyridine chemistries.

Preparation of pocket shaped microfiltration membranes with binary porous structures.

Highly permeable pocket-shaped microfiltration membranes with binary porous structures, which are composed of brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO), were prepared on needles by breath figure (BF) and colloidal crystal template (CCT) methods. In colloidal crystal templates, the membrane pore size in the bottom layer was adjusted by SiO2 microsphere diameter in the colloidal crystal template, while that in the top layer was adjusted by changing the BPPO concentration. The permeability of the binary porous membrane prepared by BF and CCT methods was higher than that of membranes only prepared by the BF method. Due to high permeability and antifouling properties, the pocket shaped binary porous membrane was connected to a syringe and used as a filter film in microfiltration and sample preparation fields.

GeneXpert: A new tool for the rapid detection of rifampicin resistance in mycobacterium tuberculosis.

OBJECTIVE: To evaluate the diagnostic accuracy of GeneXpert assay for the detection of rifampicin resistance in mycobacterium tuberculosis using conventional drug susceptibility testing as gold standard. METHODS: This cross-sectional study was conducted at Jinnah Hospital, Lahore, / Allama Iqbal Medical College, Lahore, Pakistan, from January 2012 to December 2014, and comprised clinically and radiologically diagnosed tuberculosis suspected cases. Pulmonary and extra-pulmonary specimens were collected from strong tuberculosis suspects. All specimens were processed for Ziehl Neelsen staining, Lowenstein-Jensen culture and GeneXpert assay. All mycobacterium tuberculosis positive cases on Lowenstein-Jensen culture were further processed for drug susceptibility testing. RESULTS: Of the 2,200 cases, 840(49.46%) were positive for mycobacterium tuberculosis on GeneXpert assay. Of them, 134(15.6%) cases showed rifampicin resistance on GeneXpert assay. The sensitivity, specificity, positive predictive value and negative predictive value of GeneXpert assay for rifampicin resistance were 127(98.3%), 704(99.1%), 127(94.7%) and 704(99.4%), respectively, by comparing the results with drug susceptibility testing. CONCLUSIONS: GeneXpert assay was an extremely helpful diagnostic tool for the detection of rifampicin resistance in tuberculosis suspects with fairly high sensitivity and specificity along with short turnout time.

Case report: Diagnostic challenges in an adolescent case of autistic catatonia.

Catatonia is a complex neuropsychiatric syndrome involving a constellation of psychomotor disturbances including catalepsy, waxy flexibility, stupor, mutism, negativism, agitation, posturing, stereotypes, mannerisms, grimacing, echolalia, and echopraxia. Catatonia occurs in several conditions including psychotic, affective and neurodevelopmental disorders such as autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by persistent deficits in communication, social interaction, restricted interests, repetitive behaviours and sensory sensitivities. Catatonia can occur in response to life stressors such as extreme fear or threat, interpersonal conflict, tragic events or following significant loss. Those with ASD may be particularly vulnerable to the negative impact of stressors and the link between catatonia and ASD is being increasingly recognized. The overlapping features of catatonia and ASD make it difficult to differentiate often resulting in delayed or missed diagnosis. Catatonia in ASD remains a significant clinical challenge; it is difficult to diagnose and can pose debilitating difficulties for those affected. Catatonia is a treatable condition and prompt recognition is vital in securing the best possible outcome. We report a complex and unique case of a 15-year-old boy who presented with severe cognitive and functional decline with a background history of significant bullying and deterioration in his mental state. This case posed a diagnostic conundrum leading to a diagnosis of underlying ASD, anxiety and trauma.

Improvement in Inhaler Techniques After Training and Counseling in Patients With Chronic Obstructive Pulmonary Disease or Asthma.

Background Chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma significantly impair quality of life and impose a substantial burden on healthcare systems. Proper inhalation technique is important for effective management of these diseases, yet remains poorly performed by many patients. This study evaluated the impact of structured counseling and training sessions on inhaler use among patients with COPD and asthma, aiming to enhance technique correctness and disease control. Methodology This cross-sectional study analyzed 150 patients with asthma and COPD who fulfilled the inclusion criteria for inhalation techniques. Patients were counseled regarding the proper seven-step inhalation technique for each inhaler type [metered-dose inhaler (MDI), MDI with spacer, and dry powder inhaler (DPI)] through practical demonstration at baseline visits. Correct use of inhalers was assessed by a predefined checklist for each inhaler device at the baseline visit and after three months. The correctness of the inhalation technique was evaluated by scoring each of the seven steps. The disease control assessment was done using the COPD assessment test (CAT) and asthma control test (ACT) at the baseline visit and after three months. Results In this study of 150 patients, there were 97 (64.7%) males and 53 (35.3%) females. In total, 67 (44.7%) were diagnosed with asthma and 83 (55.3%) with COPD. The mean age was 45.33 ± 12.62 years. Post-counseling improvements in inhaler technique were marked, with MDI users enhancing their technique score from an average of 4.4 to 6.1, MDI with spacer from 4.56 to 6.26, and DPI from 4.92 to 6.24 (p < 0.001 for all). Disease control also showed significant gains; CAT scores decreased for MDI users from 23.4 to 20.5, MDI with spacer from 23.92 to 20.96, and DPI from 24.89 to 21.96. Concurrently, ACT scores increased for MDI users from 16.4 to 18.0 (p = 0.002), MDI with spacer from 17.29 to 19.04, and DPI from 16.42 to 18.37 (p < 0.001 for both), reflecting substantive advances in managing COPD and asthma symptoms. Furthermore, patients with primary education exhibited a significant boost in technique mastery post-counseling (p < 0.001), underscoring the potential of well-crafted counseling to transcend educational barriers in promoting effective inhaler use. Conclusions Post-counseling, inhaler technique improved significantly across all types, with MDI with spacer users demonstrating the most progress. Technique scores increased notably (p < 0.001), and disease control scores for COPD and asthma, measured by CAT and ACT, also showed significant improvements (p < 0.001). Remarkably, primary education level participants exhibited substantial technique gains post-intervention, emphasizing the effectiveness of counseling irrespective of initial educational status in enhancing inhaler use and disease management.

Thrombocytopenia and Grading of Esophageal Varices in Patients With Chronic Liver Disease.

Background Chronic liver disease (CLD) is associated with a variety of consequences, including thrombocytopenia and esophageal varices, which significantly impact patient prognosis and management. Thrombocytopenia, frequently observed in patients with CLD, may correlate with the severity of esophageal varices, a critical complication leading to variceal bleeding. Methodology A cross-sectional study was carried out in the Department of Medicine and Gastroenterology, Pak Emirates Military Hospital, Rawalpindi, from October 2021 to March 2022. The study enrolled 94 patients, aged 18-70 years, diagnosed with CLD, regardless of the cause. These patients were categorized into four groups based on platelet count: <50,000/uL, 50,000-99,999/uL, 100,000-150,000/uL, and >150,000/uL. Pearson's correlation was utilized to evaluate the association between the severity of thrombocytopenia and the grading of esophageal varices. Results A total of 94 patients were enrolled in the study, with 53 (56.4%) males and 41 (43.6%) females. The mean age of patients was 51.06 ±11.09 years. Seventeen (18.1%) had no esophageal varices, 16 (17.0%) were diagnosed with Grade I varices, 35 (37.2%) with Grade II varices, and 26 (27.7%) had Grade III varices. Most patients without varices had a platelet count above 150 x 103 (17, 18.1%). Conversely, most patients with Grade III varices (19, 20.2%) had platelet counts below 50 x 103. Patients with no esophageal varices had a mean platelet count of 173.70 ± 37.48 x 103. Among the patients, those with Grade III esophageal varices exhibited the lowest mean platelet count, recorded at 78.54 ± 24.14 x 103. These findings indicate a statistically significant difference in mean platelet counts across the various esophageal varices grades (P = 0.000). There was an inverse correlation of platelet count with the grading of esophageal varices (r = -0.645, P < 0.000). Conclusions A negative correlation was observed between the platelet count and the grading of esophageal varices, implying that as the severity of esophageal varices increased, the platelet counts proportionally decreased.

Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study.

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans. Adolescent social isolation prolonged glucocorticoid elevation, leading to long-lasting postpartum behavioral changes in female mice. These changes were unresponsive to current PPD treatments but improved with post-delivery glucocorticoid receptor antagonist treatment. Childhood/adolescent stress significantly impacted HPA axis dysregulation and PPD in human females. Repurposing glucocorticoid receptor antagonists for some cases of treatment-resistant PPD may be considered.

IoT-fog-based healthcare 4.0 system using blockchain technology.

Real-time tracking and surveillance of patients' health has become ubiquitous in the healthcare sector as a result of the development of fog, cloud computing, and Internet of Things (IoT) technologies. Medical IoT (MIoT) equipment often transfers health data to a pharmaceutical data center, where it is saved, evaluated, and made available to relevant stakeholders or users. Fog layers have been utilized to increase the scalability and flexibility of IoT-based healthcare services, by providing quick response times and low latency. Our proposed solution focuses on an electronic healthcare system that manages both critical and non-critical patients simultaneously. Fog layer is distributed into two halves: critical fog cluster and non-critical fog cluster. Critical patients are handled at critical fog clusters for quick response, while non-critical patients are handled using blockchain technology at non-critical fog cluster, which protects the privacy of patient health records. The suggested solution requires little modification to the current IoT ecosystem while decrease the response time for critical messages and offloading the cloud infrastructure. Reduced storage requirements for cloud data centers benefit users in addition to saving money on construction and operating expenses. In addition, we examined the proposed work for recall, accuracy, precision, and F-score. The results show that the suggested approach is successful in protecting privacy while retaining standard network settings. Moreover, suggested system and benchmark are evaluated in terms of system response time, drop rate, throughput, fog, and cloud utilization. Evaluated results clearly indicate the performance of proposed system is better than benchmark.

Effective Strategies for Developing Potent, Broad-Spectrum Antibacterial and Wound Healing Promotion from Short-Chain Antimicrobial Peptides.

Traumatic multidrug resistant bacterial infections are the most lethal threat to wound healing. Antimicrobial peptides have been widely used in the antimicrobial field for their good biocompatibility and resistance to multidrug-resistant bacteria. In this work, bacterial membranes of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were extracted and immobilized on homemade silica microspheres to make a bacterial membrane chromatography stationary phase in order to quickly screen for peptides with antibacterial effects. The antimicrobial peptide was then successfully screened using bacterial membrane chromatography from a library of peptides synthesized by the one-bead-one-compound method. The antimicrobial peptide was effective in better shielding both Gram-positive and Gram-negative bacteria. Based on this antimicrobial peptide (RWPIL), we have developed an antimicrobial hydrogel with a backbone of this antimicrobial peptide and oxidized dextran (ODEX). Owing to the interlinkage between the aldehyde group in oxidized dextran and the amine group from the trauma tissue, the hydrogel extends over the irregular obverse of the skin defect and promotes epithelial cell adhesion. Based on the histomorphological analysis, we confirmed that the RWPIL-ODEX hydrogel exerts a powerful therapeutic effect in a wound infection model. In conclusion, we have developed a new antimicrobial peptide, RWPIL, and a hydrogel based on the peptide that kills multidrug-resistant bacteria parasitic on wounds and promotes wound healing.

Efficient photocatalytic degradation of Rhodamine B dye using solar light-driven La-Mn co-doped Fe2O3 nanoparticles.

This work aims to develop a highly efficient solar light-induced photocatalyst based on La-Mn co-doped Fe2O3 nanoparticles. Pure Fe2O3 and La-Mn co-doped Fe2O3 nanoparticles were fabricated by a simple co-precipitation method. The photocatalysts were analyzed for their morphological, structural, and magnetic characteristics. Scanning electron microscopy analysis demonstrated the formation of semi-spherical nanoparticles along with small aggregations. The size of nanoparticles was measured using a transmission electron microscope and found in the range of 42-49 nm. The crystalline nature and geometry of synthesized nanoparticles were investigated using X-ray diffraction analysis. Due to the incorporation of La-Mn, the saturation magnetization and remanent magnetization of the nanoparticles decreased from 6.17 to 2.89 emu/g and 1.15 to 0.52 emu/g, respectively, while the coercivity was reduced from 756.72 to 756.67 Oe. The surface area of nanoparticles was increased from 77.93 to 87.45 m2/g as a result of La-Mn co-doping. The photocatalytic performance of the Fe2O3, La0.1Mn0.3Fe1.6O3, and La0.2Mn0.2Fe1.6O3 catalysts was assessed by their capability to degrade Rhodamine B (RhB) under solar light illumination. La0.2Mn0.2Fe1.6O3 displayed exceptional degradation performance, degrading RhB to 91.78% in 240 min, in comparison to La0.1Mn0.3Fe1.6O3 (71.09%) and pristine Fe2O3 (58.21%) under specified reaction conditions ((RhB) = 50 ppm; (catalyst) = 40 mg/L; pH = 7; T = 25 °C)). RhB degradation was affected by changing pH, catalytic dosage, dye concentration, and temperature. The degradation of RhB was found to be pseudo-1st order kinetics. The exceptional photocatalytic performance of La0.2Mn0.2Fe1.6O3 catalysts showed that the synthesized nanoparticles could be effectively utilized to remove organic pollutants from industrial wastewater.

The lymphatic endothelium-derived follistatin: activin A axis regulates neutrophil motility in response to Pseudomonas aeruginosa.

The lymphatic system plays an active role during infection, however the role of lymphatic-neutrophil interactions in host-defense responses is not well understood. During infection with pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and Yersinia pestis, neutrophils traffic from sites of infection through the lymphatic vasculature, to draining lymph nodes to interact with resident lymphocytes. This process is poorly understood, in part, due to the lack of in vitro models of the lymphatic system. Here we use a 3D microscale lymphatic vessel model to examine neutrophil-lymphatic cell interactions during host defense responses to pathogens. In previous work, we have shown that follistatin is secreted at high concentrations by lymphatic endothelial cells during inflammation. Follistatin inhibits activin A, a member of the TGF-ß superfamily, and, together, these molecules form a signaling pathway that plays a role in regulating both innate and adaptive immune responses. Although follistatin and activin A are constitutively produced in the pituitary, gonads and skin, their major source in the serum and their effects on neutrophils are poorly understood. Here we report a microfluidic model that includes both blood and lymphatic endothelial vessels, and neutrophils to investigate neutrophil-lymphatic trafficking during infection with P. aeruginosa. We found that lymphatic endothelial cells produce secreted factors that increase neutrophil migration toward P. aeruginosa, and are a significant source of both follistatin and activin A during Pseudomonas infection. We determined that follistatin produced by lymphatic endothelial cells inhibits activin A, resulting in increased neutrophil migration. These data suggest that the follistatin:activin A ratio influences neutrophil trafficking during infection with higher ratios increasing neutrophil migration.

Immunotherapy: cancer immunotherapy and its combination with nanomaterials and other therapies.

Immunotherapy is a new type of tumor treatment after surgery, radiotherapy and chemotherapy, and can be used to manage and destroy tumor cells through activating or strengthening the immune response. Immunotherapy has the benefits of a low recurrence rate and high specificity compared to traditional treatment methods. Immunotherapy has developed rapidly in recent years and has become a research hotspot. Currently, chimeric antigen receptor T-cell immunotherapy and immune checkpoint inhibitors are the most effective tumor immunotherapies in clinical practice. While tumor immunotherapy brings hope to patients, it also faces some challenges and still requires continuous research and progress. Combination therapy is the future direction of anti-tumor treatment. In this review, the main focus is on an overview of the research progress of immune checkpoint inhibitors, cellular therapies, tumor vaccines, small molecule inhibitors and oncolytic virotherapy in tumor treatment, as well as the combination of immunotherapy with other treatments.

Mortality Rates and autopsy findings in fat embolism syndrome complicating sickle cell disease.

Fat embolism syndrome is a rare but underdiagnosed complication of sickle cell disease associated with high morbidity and mortality. It affects predominantly patients with a previously mild course of their illness and those of non-SS genotypes while there is possibly an association with infection with human parvovirus B19 (HPV B19). Here, we present the mortality rates and autopsy findings of all reported cases to date. A systematic review has revealed 99 published cases in the world literature with a mortality rate of 46%. Mortality varied greatly according to the time of reported cases with no survivors in the 1940s, 1950s or 1960s and no deaths since 2020. 35% of cases had previously undiagnosed sickle cell disease and the latter was only identified at autopsy after developing fat embolism with a fatal outcome. 20% of cases reported after 1986 tested positive for HPV B19 with an associated mortality of 63% whereas in cases that have not documented HPV B19 infection the mortality was 32%. The organs most often staining positive for fat were the kidneys, lungs, brain and heart whereas ectopic haematopoietic tissue was found in 45% of the examined lung specimens.