Agarose Cryogels Loaded with Polydopamine Microspheres for Sustainable Wound Care with Enhanced Hemostatic and Antioxidant Properties.

Excessive bleeding presents a grave risk to life, especially in scenarios involving deep wounds such as those inflicted by gunshots and accidental stabs. Despite advancements in wound care management, existing commercial hemostatic agents have limitations, necessitating the development of enhanced solutions. In this study, we developed cryogels using agarose and polydopamine microspheres as a hemostatic dressing to effectively manage profuse bleeding. The resulting cryogels demonstrated impressive attributes, such as high absorption capacity (>4000%), shape recovery ability, antioxidant properties, and excellent biocompatibility in mammalian cell lines. Particularly noteworthy was the rapid blood clotting observed in vitro, with the agarose/PDA cryogels achieving complete clotting within just 90 s. Subsequent validation in the rat trauma model further underscored their hemostatic efficacy, with clotting times of 40 and 53 s recorded in tail amputation and liver puncture models, respectively. The porous structure and hydrophilicity of the cryogels facilitated superior blood absorption and retention, while the amine groups of polydopamine played a pivotal role in enhancing blood clotting activity. This study represents a significant step forward in utilizing agarose/polydopamine cryogels as advanced materials for hemostatic wound dressings, promising an impactful contribution to wound therapy.

Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies.

BACKGROUND: BMS-986156 is an agonist of the glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) and promotes increased effector T-cell activation. Combined anti-GITR, anti-programmed death-1, anti-cytotoxic T-lymphocyte-associated protein 4 antibodies and radiotherapy improve tumor control in preclinical studies. Herein we describe the results of the safety and efficacy of BMS-986156+ipilimumab or nivolumab with/without stereotactic ablative radiotherapy (SABR) in patients with advanced solid cancers (NCT04021043). METHODS: This open-label, multigroup, single-center phase I/II study enrolled patients with histologically-confirmed stage IV solid cancers resistant to standard treatments. Group 1 (G1, n=20) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (30 mg as dose level 1 (L1) or 100 mg as dose level 2 (L2)), every 3 weeks (Q3W). Group 2 (G2, n=10) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (dose as determined in G1, Q3W) with SABR (50 Gy/4 fx or 60-70 Gy/10 fx to liver/lung lesions. Group 3 (G3, n=20) received four cycles of nivolumab (480 mg) plus BMS-986156 (30 mg), every 4 weeks with SABR. Maintenance nivolumab could be given up to 2 years. Tumor responses were assessed every 1-3 months until progression, using immune-related response criteria. RESULTS: 50 patients were enrolled between 10/2019 and 12/2021. Patients received a median of 3 (IQR 2-4.25) initial treatment cycles. 100 mg BMS-986156 with ipilimumab was tolerated well. Five discontinued BMS-986156 with ipilimumab due to treatment-related adverse events (TRAEs), with three in G1/L1, one in G1/L2 and one in G2, respectively. 22 patients (44%) experienced Grade 1-3 TRAEs (6, 4, 5, 7 patients for G1/L1, G1/L2, G2, G3). Six (12%) had Grade 3 TRAEs (2, 2, 1, 1 for G1/L1, G1/L2, G2, G3), with elevated alanine aminotransferase (n=3, in G1/L2, G2 and G3) and aspartate aminotransferase (n=2, in G2 and G3) being the most common. There was no Grade 4-5 TRAEs. Overall, 19/39 (48.7%) patients eligible for efficacy analysis had stable disease and 3 (7.7%) achieved a partial response. Out-of-field (abscopal) disease control rate (ACR) and out-of-field (abscopal) response rate (ARR) were 38.5% and 7.7%, respectively, with the highest ACR (50%, 9/18) and ARR (11.1%, 2/18) in G3. CONCLUSIONS: BMS-986156 was well-tolerated with ipilimumab, nivolumab, with or without SABR. Outcomes were encouraging in this population, as more than half of patients had stable disease/partial response.

Batteries Within Diabetes Devices: A Narrative Review on Recycling, Environmental, and Sustainability Perspective.

The adoption of diabetes technology for the management of type 1 and insulin-treated type 2 diabetes has greatly increased. The annual volume of discarded continuous glucose monitoring (CGM) devices, considering only Dexcom and Freestyle Libre brands, totals more than 153 million units and Omnipod® contributes an additional estimated 43.8 million units.Although these technologies are clinically effective, their environmental impact is unknown. Batteries are a pivotal, yet often overlooked, component in diabetes technologies and can exert a detrimental impact on the environment.In this commentary article, we explore the environmental impact of batteries used in diabetes devices. Furthermore, we highlight various strategies, including recycling of used batteries and alternative design approaches, that may reduce the environmental burden, as they become the ubiquitous standard of care for people with diabetes.

Effect of fenugreek (Trigonella foenum-graecum L.) seed extract on glycemic index, in vitro digestibility, and physical characterization of wheat (Triticum aestivum L.) starch.

Diabetes is a major health concern and is approaching epidemic proportions worldwide. In 2021, diabetes mellitus was responsible for 6.7 million deaths across the globe. Mortality due to diabetes is predicted to rise nearly 10-fold by 2030 and 783 million by 2045. Wheat starch, which constitutes about 70% of the endosperm, is a key component of wheat grain. The rapid hydrolysis of wheat starch can result in elevated postprandial glucose levels, leading to diabetes. The increase in blood glucose levels is primarily due to carbohydrate hydrolysis, catalyzed by the enzymes α-amylase and α-glucosidase. Although various medications are available for treating diabetes, most of them are costly and may lead to adverse effects. Natural herbs like fenugreek are recommended in traditional medicine for regulating blood glucose levels. This investigation aimed to study the effect of fenugreek seed extract (FSE) on in vitro starch hydrolysis by pancreatic α-amylase and the ultrastructure of starch. Wheat cultivars were characterized for their total starch, amylose content, and resistant starch content, and were screened for their predicted glycemic index. Microscopic studies were conducted to analyze the size and shape of starch granules and to compare native starch with starch treated with FSE. Significant inhibition of enzymatic starch hydrolysis was observed with FSE, with the maximum inhibitory effect caused by 0.2% FSE. These findings suggest that fenugreek could play a role in controlling blood glucose levels by reducing wheat starch hydrolysis and could be effective in managing diabetes.

A sex-specific homologue of waprin is essential for embryonic development in the red flour beetle, Tribolium castaneum.

Waprin, a WAP (Whey acidic protein) domain-containing extracellular secretory protein, is widely known for its antibacterial properties. In this study, a waprin homologue (Tc_wapF) expressing in a female-specific manner was identified in Tribolium castaneum, through the analysis of sex-specific transcriptomes. Developmental- and tissue-specific profiling revealed the widespread expression of Tc_wapF in adult female tissues, particularly in the ovary, gut and fatbody. This female-specific expression of Tc_wapF is not regulated by the classical sex-determination cascade of T. castaneum, as we fail to get any attenuation in Tc_wapF transcript levels in Tcdsx and Tctra (key players of sex determination cascade of T. castaneum) knockdown females. RNA interference-mediated knockdown of Tc_wapF in females led to the non-hatching of eggs laid by these females, suggesting the crucial role of Tc_wapF in the embryonic development in T. castaneum. This is the first report on the identification of a sex-specific waprin homologue in an insect and its involvement in embryonic development. Future investigations on the functional conservation of insect waprins and their mechanistic role in embryonic development can be exploited for improving pest management strategies.

Post-Translational Modifications Control The Signal At The Crossroads Of Plant-Pathogen Interaction.

The co-evolution of plants and pathogens has enabled them to 'outsmart' each other by promoting their own defense responses and suppressing that of the other. While plants are reliant on their sophisticated immune signalling pathways, pathogens make use of effector proteins to achieve the objective. This entails rapid regulation of the underlying molecular mechanisms for prompt induction of the associated signalling events in both plants as well as pathogens. The last decade has witnessed the emergence of post-translational modification (PTM) of proteins as key players in modulating cellular responses. Their ability to expand the functional diversity of the proteome and induce rapid changes at the appropriate time enables them to play crucial roles in the regulation of plant-pathogen interactions. Therefore, this review will delve into the intricate interplay of five major PTMs in plant defense and pathogen countermeasures. The review discusses how plants employ PTMs to fortify their immune networks, and how pathogen effectors utilize/target host modification systems to gain entry into the plant and cause disease. The review also underscores the need for identification of newer PTMs and proposes to use PTM machineries as potential targets for genome editing approaches.

Fabrication and characterization of multi-layered coaxial agar-based electrospun biocomposite mat, novel replacement for transdermal patches.

In the performed study, a novel fabrication of agar-based nanofibers was electrospun in an asymmetric bilayer dressing for biomedical transdermal patches. The optimal parameters for the fabrication of agar-based nanofibers after optimization were a feed rate of 10 µL/min, a 7 cm collector-to-nozzle distance, a 15 kV applied voltage, and a 700-rpm rotating collector speed. Coaxial nanofibers, as a second asymmetric layer, were produced using polyvinyl alcohol (PVA) with cephalexin hydrate, an antibacterial drug, as the core and agar-PCL as the sheath. The morphology of the developed uniaxial and coaxial nanofibrous layers was analysed using a scanning electron microscope and transmission electron microscopy, respectively. For the formation of bilayer asymmetric structures, the agar-PCL uniaxial layer was fabricated over the layer of coaxial PVA and agar-PCL layers for sustained drug release. The agar-based nanofibrous mats exhibited tensile strength of 7 MPa with 40 % elongation failure, 8-fold increased swelling, enhanced wettability (60° contact angle), and a moisture transmission rate of 2174 g/m2/day. The developed coaxial bilayer mats exhibited antimicrobial activity, hemocompatibility, and cytocompatibility. Overall, this novel agar nanofibrous dressing offers promising potential for advanced biomedical applications, particularly as transdermal patches for efficient drug delivery systems.

Determination of Sample Size for Different Clinical Study Designs.

AIM: This study illustrates parameters, procedures, and calculations for the statistical determination of sample size for different clinical study designs. MATERIALS AND METHODS: In any research process, the sample size is an important consideration for the implementation of the planned study. From time to time, literature on sample size has been documented in the medical literature. However, the situations covered under them lack comprehensiveness in terms of different study designs, demonstration of calculations, and overreliance on statistical software. RESULTS: The present study provides various facets of sample size determination, such as prerequisite parameters, mathematical formulation, and calculations for clinical study designs [descriptive studies, randomized controlled trials (RCT), correlational studies, comparison of multiple outcomes, survival analysis, sensitivity, and specificity], which will be quite useful. CONCLUSION: This communication will be a good education and learning source for medical professionals to pick and choose a specific scenario and estimate the sample size.

Multifunctional polymeric nanofibrous scaffolds enriched with azilsartan medoxomil for enhanced wound healing.

A prolonged and compromised wound healing process poses a significant clinical challenge, necessitating innovative solutions. This research investigates the potential application of nanotechnology-based formulations, specifically nanofiber (NF) scaffolds, in addressing this issue. The study focuses on the development and characterization of multifunctional nanofibrous scaffolds (AZL-CS/PVA-NF) composed of azilsartan medoxomil (AZL) enriched chitosan/polyvinyl alcohol (CS/PVA) through electrospinning. The scaffolds underwent comprehensive characterization both in vitro and in vivo. The mean diameter and tensile strength of AZL-CS/PVA-NF were determined to be 240.42 ± 3.55 nm and 18.05 ± 1.18 MPa, respectively. A notable drug release rate of 93.86 ± 2.04%, was observed from AZL-CS/PVA-NF over 48 h at pH 7.4. Moreover, AZL-CS/PVA-NF exhibited potent antimicrobial efficacy for Staphylococcus aureus and Pseudomonas aeruginosa. The expression levels of Akt and CD31 were significantly elevated, while Stat3 showed a decrease, indicating a heightened tissue regeneration rate with AZL-CS/PVA-NF compared to other treatment groups. In vivo ELISA findings revealed reduced inflammatory markers (IL-6, IL-1ß, TNF-α) within treated skin tissue, implying a beneficial effect on injury repair. The comprehensive findings of the present endeavour underscore the superior wound healing activity of the developed AZL-CS/PVA-NF scaffolds in a Wistar rat full-thickness excision wound model. This indicates their potential as novel carriers for drugs and dressings in the field of wound care.

Prevalence and Risk Factors of Cerebral Microbleeds in Community-Dwelling Adults in Urban Delhi.

BACKGROUND: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. METHODS: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. RESULTS: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (60-70 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. CONCLUSION: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs.

Is Single-Site Radiation Therapy Enough to Augment the Immune System and Enhance Immunotherapy for Metastatic Disease?

Despite the promise of combining immunotherapy and radiotherapy (RT) for metastatic cancers, existing randomized data have not been consistent on whether RT to a single irradiated site improves clinical outcomes. Mechanistically, this could result from a low quantity/diversity of tumor antigens released for immune detection, immunosuppressive molecules released by tumor masses, and the lack of immune infiltration into tumor bulk. Herein, multi-site RT is discussed as a potential solution, given that it can directly improve upon each of the mechanistic issues. Just as it is illogical to use systemic therapy alone in place of a dedicated local therapeutic option (e.g., RT) for most stage II-III malignancies, so too is illogical to irradiate one site only in case of metastatic neoplasms instead of implementing systemic therapy and/or multi-site RT. Although it may theoretically be possible to address all systemic disease with systemic therapy, that notion assumes that all areas of systemic disease will be responsive to systemic therapy in the first place. However, in reality, certain sites may develop innate or acquired resistance to systemic therapy, hence opening the door to multi-site localized treatment strategies. Further investigation is required to address whether multi-site RT would be effective in the setting of suboptimal immune function and/or resistance/refractoriness to multiple prior systemic therapies. Methods to improve the effectiveness of multi-site RT are also discussed, such as ablatively-/definitively-dosed RT, along with staggered timing of RT administration (pulsed RT).

Differences in Patterns of Care and Referral Between Proton and Photon Therapy.

Purpose: To report demographic and clinical characteristics of patients who were more likely to receive proton beam therapy (PBT) than photon therapy from facilities with access to proton centers. Materials and Methods: We utilized the national cancer database to identify the facilities with access to PBT between 2004 and 2015 and compared the relative usage of photons and PBT for demographic and clinical scenarios in breast, prostate, and nonsmall cell cancer. Results: In total, 231 facilities with access to proton centers accounted for 168 323 breast, 39 975 lung, and 77 297 prostate cancer patients treated definitively. Proton beam therapy was used in 0.5%, 1.5%, and 8.9% of breast, lung, and prostate cases. Proton beam therapy was correlated with a farther distance traveled and longer start time from diagnosis for each site (P < .05).For breast, demographic correlates of PBT were treatment in the west coast (odds ratio [OR] = 4.81), age <60 (OR = 1.25), white race (OR = 1.94), and metropolitan area (OR = 1.58). Left-sided cancers (OR = 1.28), N2 (OR = 1.71), non-ER+/PR+/Her2Neu- cancers (OR = 1.24), accelerated partial breast irradiation (OR = 1.98), and hypofractionation (OR = 2.35) were predictors of PBT.For nonsmall cell cancer, demographic correlates of PBT were treatment in the south (OR = 2.6), metropolitan area (OR = 1.72), and Medicare insurance (OR = 1.64). Higher comorbid score (OR = 1.36), later year treated (OR = 3.16), and hypofractionation (not SBRT) (OR = 3.7) were predictors of PBT.For prostate, correlates of PBT were treatment in the west coast (OR = 2.48), age <70 (OR = 1.19), white race (OR = 1.41), metropolitan area (OR = 1.25), higher income/education (OR = 1.25), and treatment at an academic center (OR = 33.94). Lower comorbidity score (OR = 1.42), later year treated (OR = 1.37), low-risk disease (OR = 1.45), definitive compared to postoperative (OR = 6.10), and conventional fractionation (OR = 1.64) were predictors of PBT. Conclusion: Even for facilities with established referrals to proton centers, PBT utilization was low; socioeconomic status was potentially a factor. Proton beam therapy was more often used with left-sided breast and low-risk prostate cancers, without a clear clinical pattern in lung cancer.

Stereotactic radiotherapy vs whole brain radiation therapy in EGFR mutated NSCLC: Results & reflections from the prematurely closed phase III HYBRID trial.

BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.

Myeloid-specific ferritin light chain deletion does not exacerbate sepsis-associated AKI.

Sepsis-associated acute kidney injury (SA-AKI) is a key contributor to the life-threatening sequelae attributed to sepsis. Mechanistically, SA-AKI is a consequence of unabated myeloid cell activation and oxidative stress that induces tubular injury. Iron mediates inflammatory pathways directly and through regulating the expression of myeloid-derived ferritin, an iron storage protein comprising ferritin light (FtL) and ferritin heavy chain (FtH) subunits. Previous work revealed that myeloid FtH deletion leads to a compensatory increase in intracellular and circulating FtL and is associated with amelioration of SA-AKI. We designed this study to test the hypothesis that loss of myeloid FtL and subsequently, circulating FtL will exacerbate the sepsis-induced inflammatory response and worsen SA-AKI. We generated a novel myeloid-specific FtL knockout mouse (FtLLysM-/-) and induced sepsis via cecal ligation and puncture or lipopolysaccharide endotoxemia. As expected, serum ferritin levels were significantly lower in the knockout mice, suggesting that myeloid cells dominantly contribute to circulating ferritin. Interestingly, although sepsis induction led to a marked production of pro- and anti-inflammatory cytokines, there was no statistical difference between the genotypes. There was a similar loss of kidney function, as evidenced by a rise in serum creatinine and cystatin C and renal injury identified by expression of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Finally, RNA sequencing revealed upregulation of pathways for cell cycle arrest and autophagy postsepsis, but no significant differences were observed between genotypes, including in key genes associated with ferroptosis, an iron-mediated form of cell death. The loss of FtL did not impact sepsis-mediated activation of NF-κB or HIF-1a signaling, key inflammatory pathways associated with dysregulated host response. Taken together, while FtL overexpression was shown to be protective against sepsis, the loss of FtL did not influence sepsis pathogenesis.NEW & NOTEWORTHY Hyperferritinemia in sepsis is often associated with a proinflammatory phenotype and poor prognosis. We previously showed the myeloid deletion of FtH results in a compensatory increase in FtL and is associated with reduced circulating cytokines and decreased rates of SA-AKI in animal sepsis models. Here, we show that myeloid deletion of FtL does not impact the severity of SA-AKI following CLP or LPS, suggesting that FtH plays the predominant role in propagating myeloid-induced proinflammatory pathways.

Insights into the role of SUMO in regulating drought stress responses in pigeonpea (Cajanus cajan).

KEY MESSAGE: We have identified and analyzed 28 SUMO-pathway proteins from pigeonpea. Enhanced transcripts of pathway genes and increased SUMO conjugation under drought signifies the role of SUMO in regulating stress. Being a protein-rich and nutrient-dense legume crop, pigeonpea (Cajanus cajan) holds a vital position in a vegetarian meal. It is a resilient crop capable of striving in harsh climates and provides a means of subsistence to small-holding farmers. Nevertheless, extremes of water scarcity and drought conditions, especially during seedling and reproductive stages, remains a major issue severely impacting the growth and overall productivity of pigeonpea. Small ubiquitin-like modifier (SUMO), a post-translational modification system, plays a pivotal role in fortifying plants against stressful conditions by rapid reprogramming of molecular events. In this study, we have scanned the entire pigeonpea genome and identified 28 candidates corresponding to SUMO machinery components of pigeonpea. qRT-PCR analysis of different SUMO machinery genes validated their presence under natural conditions. The analysis of the promoters of identified SUMO machinery genes revealed the presence of abiotic stress-related cis-regulatory elements highlighting the potential involvement of the genes in abiotic stress responses. The transcript level analysis of selected SUMO machinery genes and global SUMO status of pigeonpea proteins in response to drought stress suggests an integral role of SUMO in regulating drought stress conditions in pigeonpea. Collectively, the work puts forward a detailed in silico analysis of pigeonpea SUMO machinery candidates and highlights the essential role of SUMOylation in drought stress responses. Being the first report on a pulse crop, the study will serve as a resource for devising strategies for counteracting drought stress in pigeonpea that can be further extended to other pulse crops.

Multifunctional 58S Bioactive Glass/Silver/Cerium Oxide-Based Biocomposites with Effective Antibacterial, Cytocompatibility, and Mechanical Properties.

58S bioactive glass (BG) has effective biocompatibility and bioresorbable properties for bone tissue engineering; however, it has limitations regarding antibacterial, antioxidant, and mechanical properties. Therefore, we have developed BGAC biocomposites by reinforcing 58S BG with silver and ceria nanoparticles, which showed effective bactericidal properties by forming inhibited zones of 2.13 mm (against Escherichia coli) and 1.96 mm (against Staphylococcus aureus; evidenced by disc diffusion assay) and an increment in the antioxidant properties by 39.9%. Moreover, the elastic modulus, hardness, and fracture toughness were observed to be increased by ∼84.7% (∼51.9 GPa), ∼54.5% (∼3.4 GPa), and ∼160% (∼1.3 MPam1/2), whereas the specific wear rate was decreased by ∼55.2% (∼1.9 × 10-11 m3/Nm). X-ray diffraction, high-resolution transmission electron microscopy, and field emission scanning electron microscopy confirmed the fabrication of biocomposites and the uniform distribution of the nanomaterials in the BG matrix. The addition of silver nanoparticles in the 58S BG matrix (in BGA) increased mechanical properties by composite strengthening and bactericidal properties by damaging the cytoplasmic membrane of bacterial cells. The addition of nanoceria in 58S BG (BGC) increased the antioxidant properties by 44.5% (as evidenced by the 2,2-diphenyl-1-picrylhydrazyl assay). The resazurin reduction assay and MTT assay confirmed the effective cytocompatibility for BGAC biocomposites against mouse embryonic fibroblast cells (NIH3T3) and mouse bone marrow stromal cells. Overall, BGAC resulted in mechanical properties comparable to those of cancellous bone, and its effective antibacterial and cytocompatibility properties make it a good candidate for bone healing.

Reconciling the discrepancies in randomized data of combining immunotherapy and radiation therapy: Not all radiotherapy is created equal.

It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof. This work seeks to address these discrepancies, and uses the lessons learned from both positive and negative trials, including the most cutting-edge data available, in order to guide future clinical trial design and clarify the ideal/expected role of combinatorial therapy going forward. Because RT offers two distinct contributions (cytoreductive (local) effects & immune-stimulating (systemic) effects), RT should complement immunotherapy by addressing immunotherapy-resistant clones, and immunotherapy should complement RT by addressing RT-resistant or out-of-field clones. RT is not merely a single "drug", but rather a constellation of diverse "drugs" that can be varied based on dose regimens, previous systemic therapy regimens, number of irradiated sites, treatment intent/location/timing, tumor biology, and individual patient immunological circumstances. These factors are discussed as an important explanation for the discrepancies in results of various randomized trials in heterogeneous populations and clinical settings, and these discrepancies may continue until trials of more uniform circumstances are designed to use particular RT paradigms that meaningfully add value to systemic therapy.

Preparation and assessment of agar/TEMPO-oxidized bacterial cellulose cryogels for hemostatic applications.

In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material.