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Corneal blindness is a significant reason for visual impairment globally. Researchers have been investigating several methods for corneal regeneration in order to cure these patients. Biomaterials are favored due to their biocompatibility and capacity to promote cell adhesion. A variety of natural and synthetic biomaterials, along with decellularized cornea, have been employed in corneal wound healing. Commonly utilized natural biomaterials encompass proteins such as collagen, gelatin, and silk fibroin (SF), as well as polysaccharides including alginate, chitosan (CS), hyaluronic acid (HA), and cellulose. Synthetic biomaterials primarily consist of polyvinyl alcohol (PVA), poly(ε-caprolactone) (PCL), and poly (lactic-co-glycolic acid) (PLGA). Bio-based materials and their composites are primarily utilized as hydrogels, films, scaffolds, patches, nanocapsules, and other formats for the treatment of blinding ocular conditions, including corneal wounds, corneal ulcers, corneal endothelium, and stromal defects. This review attempts to summarize in vitro, preclinical, and clinical trial studies relevant to corneal regeneration using biomaterials within the last five years, and expect that these experiences and outcomes will inspire and provide practical strategies for the future development of biomaterials for corneal regeneration. Furthermore, potential improvements and difficulties for these biomaterials are discussed., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose of Review: This article aims to offer a comprehensive review of optimal integrative medicine practices for geriatric oncology patients. Given the aging population and the global rise in cancer incidence, it is crucial to identify evidence-based modalities and employ an integrated approach to enhance cancer outcomes and quality of life in older adults., Recent Findings: It has been predicted that 20.5% (6.9 million) of new cancer cases in 2050 will occur in adults over 80 years old. 1 The increasing focus on lifestyle factors in healthy aging has shed light on various overlooked areas of significance. Notably, anti-inflammatory diets and the promotion of a healthy gut microbiome have demonstrated significant impacts on overall health outcomes, bolstering the body's innate capacity to combat disease. This review delves into further evidence and extrapolation concerning integrative approaches and their influence on cancer outcomes and older adults quality of life. The complexity and unique nature of cancer in older adults requires a wide range of support from medical providers. Incorporating various integrative techniques as part of cancer treatment and side effect support can improve health outcomes and patient's quality of life. Familiarity with the lifestyle interventions and other topics explored in this review equips healthcare providers to offer tailored and holistic care to geriatric patients navigating cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Disease treatment and prevention have improved the human lifespan. Current studies on aging, such as the biological clock and senolytic drugs have focused on the medical treatments of various disorders and health maintenance. However, to efficiently extend the human lifespan to its theoretical maximum, medicine can take a further proactive approach and identify the inapparent disorders that affect the gestation, body growth, and reproductive stages of the so-called "healthy" population. The goal is to upgrade the standard health status to a new level by targeting the inapparent disorders. Thus, future research can shift from reaction, response, and prevention to proactive, quality promotion and vigor prolonging; from single disease-oriented to multiple dimension protocol for a healthy body; from treatment of symptom onset to keep away from disorders; and from the healthy aging management to a healthy promotion design beginning at the birth., (© 2024 Wiley‐VCH GmbH.)

Eutectic alloys (EAs) with superior fluidity are known to be the easiest to cast into high-quality ingots, making them the alloys of choice for making large-sized structural parts. However, conventional EAs (CEAs) have never reached strength-ductility combinations on par with the best in other alloy categories. Via thermomechanical processing of cast Ni-32.88wt%Fe-9.53wt%Al CEAs, a cocoon-like nano-meshed (as fine as 26 nm) network of dislocations (CNN-D) is produced via recovery annealing, through the rearrangement of cold-work-accumulated dislocations anchored by dense pre-existing nanoprecipitates. In lieu of traditional plasticity mechanisms, such as TWIP and TRIP, the CNN-D is particularly effective in eutectic lamellae with alternating phases, as it instigates nanometer-spaced planar slip bands that not only dynamically refine the microstructure but also transmit from the FCC (face-centered-cubic) layers into the otherwise brittle B2 layers. These additional mechanisms for strengthening and strain hardening sustain stable tensile flow, resulting in a striking elevation of both strength and ductility to outrank not only all previous CEAs, but also the state of the art-additively manufactured eutectic high-entropy alloys. The CNN-D thus adds a novel microstructural strategy for performance enhancement, especially for compositionally complex alloys that increasingly make use of nanoprecipitates or local chemical order., (© 2024 Wiley‐VCH GmbH.)

Aqueous potassium-ion batteries (AKIBs) are considered promising electrochemical energy storage systems owing to their high safety and cost-effectiveness. However, the structural degradation resulting from the repeated accommodation of large K-ions and the dissolution of active electrode materials in highly dielectric aqueous electrolytes often lead to unsatisfactory electrochemical performance. This study introduces a high-entropy Prussian blue analog (HEPBA) cathode material for AKIBs, demonstrating significantly enhanced structural stability and reduced dissolution. The HEPBA exhibits a highly reversible specific capacity of 102.4 mAh g -1 , with 84.4% capacity retention after undergoing 3448 cycles over a duration of 270 days. Mechanistic insights derived from comprehensive experimental investigations, supported by theoretical calculations, reveal that the HEPBA features a robust structure resistant to dissolution, a solid-solution reaction pathway with negligible volume variation during charge-discharge, and efficient ion transport kinetics characterized by a reduced band gap and a low energy barrier. This study represents a measurable step forward in the development of long-lasting electrode materials for aqueous AKIBs., (© 2023 Wiley‐VCH GmbH.)

Herein an enzyme-assisted supercritical fluid extraction (EA-SFE) was developed using the enzyme mix snailase to obtain flavonols and dihydrochalcones, subgroups of flavonoids, from globally abundant waste product apple pomace. Snailase, a commercially available mix of 20-30 enzymes, was successfully used to remove the sugar moieties from quercetin glycosides, kaempferol glycosides, phloridzin and 3-hydroxyphloridzin. The resulting flavonoid aglycones quercetin, kaempferol, phloretin and 3-hydroxyphloretin were extracted using supercritical carbon dioxide (scCO 2 ) and minimum amounts of polar cosolvents. A sequential process of enzymatic hydrolysis and supercritical fluid extraction was developed, and the influence of the amount of snailase, pre-treatment of apple pomace, the time for enzymatic hydrolysis, the amount and type of cosolvent and the time for extraction, was studied. This revealed that even small amounts of snailase (0.25 %) provide a successful cleavage of sugar moieties up to 96 % after 2 h of enzymatic hydrolysis followed by supercritical fluid extraction with small amounts of methanol as cosolvent, leading up to 90 % of the total extraction yields after 1 h extraction time. Ultimately, a simultaneous process of EA-SFE successfully demonstrates the potential of snailase in scalable scCO 2 extraction processes for dry and wet apple pomace with satisfactory enzyme activity, even under pressurized conditions., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

his comprehensive review is designed to evaluate the anticancer properties of β-carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of β-carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural β-carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived β-carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive-enhancing effects. The current body of research emphasizes the potential of β-carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of β-carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Among the various neurodegenerative disorders, Alzheimer's disease (AD) is identified as one of primary causes of dementia in the elderly, which progresses slowly leading to cognitive decline and ability to function independently. Although various pathological mechanisms have been proposed, the exact mechanism is not yet elucidated. Numerous processes such as old age, mitochondrial dysfunction, and genetics lead to the aggregation of beta-amyloid (Aβ) as amyloid plaques and tau proteins as neurofibrillary tangles in the neurons leading to their death and destruction, finally leading to AD. The current treatment measures can only temporarily improve the symptoms, slowing cognitive decline without any effect on AD pathology for better therapeutic effect. Furthermore, the high failure rates of a number of drugs during clinical trials due to their side effects has led the researchers to focus on alternative sources for drug development. As natural ingredients were considered the primary line of treatment in the olden days, and as several medicinal plant products are also proven as effective AD targets, it will be wise to investigate those with significant ethnobotanical value as potential neuroprotectives, nootropics or memory boosters. Throughout the study, propanoids, glycosides, iridoids, carotenoids and flavonoids that show potential anti-inflammatory, antioxidant, and anti-cholinesterase were also found to be inhibitors of Aβ and tau aggregation, where Saikosaponin C, Fisetin, and Morin can act as dual inhibitors. The review provides an insight in the need for proper and complete scientific evaluation of these ethnobotanically useful medicinal plants to be identified as potential leads in AD therapy., (© 2023 Wiley Periodicals LLC.)

Purpose: Recent studies claim that immune checkpoint inhibitors are effective in defective mismatch repair (dMMR) cancers. This raises the question of whether similar therapies are effective in PanNETs (pancreatic neuroendocrine tumors); however, in general, assessment of MMR status in PanNETs has been inconsistent in previous studies. MGMT (O6-methylguanine-DNA methyltransferase) is potentially important for guiding temozolomide (TMZ) therapy in glioblastoma. The number of reports on MGMT expression and promoter methylation in PanNETs are limited., Methods: In this study we assessed the expression of MGMT and MMR proteins MSH2, MSH6, MLH1 and PMS2 in a series of PanNETs by IHC. The methylation status of MGMT and MMR genes in a subset of PanNETs was further assessed by MS-MLPA analysis. Survival curves were constructed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Multivariate Cox proportional hazards regression models were used to determine the prognostic value of the variables., Results: According to evaluation criteria for mismatch repair defects, none of PanNETs shown nuclear staining loss for MSH2, MSH6, MLH1, and PMS2. MGMT low-intensity PanNETs were more commonly found in higher grade, higher Ki67 index and non-functional tumors (P < 0.05). In multivariate analysis, stage III-IV and low-intensity MGMT were shown to be independent risk factors for progression of PanNETs in the entire cohort, non-functioning subgroup and G2 subgroup (P < 0.05 for all). MGMT promoter methylation tended to be higher in the group with low expression of MGMT, However, methylation of MGMT did not statistically correlate with low expression of MGMT (P = 0.153)., Conclusions: In conclusion, our study suggests that decreased expression of MGMT but not MMR is associated with a higher risk of progression of pancreatic neuroendocrine tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The COVID-19 pandemic has led to significant societal disruptions, prompting the Indonesian government to implement various measures, including partial lockdowns or Community Activities Restrictions Enforcement (CARE), to curb the virus's spread. This research aims to assess the impact of various environmental parameters on Cirebon's estuaries, focusing on physical components (such as temperature, total solids [TS], and turbidity), chemical components (including pH, biochemical oxygen demand (BOD), dissolved oxygen (DO), nitrate, and phosphate), and microbiology components (specifically total coliforms). These comprehensive components have notably impacted environmental parameters during pre-, during, and post-COVID-19 pandemic based on the Water Quality Index (WQI) assessment in Cirebon's estuaries. In the port city of Cirebon, located on Java Island's northern coast, the water quality of three river estuaries Kesenden, Sukalila, and Kalijaga was analyzed before and after the CARE implementation. Water samples collected in 2019, 2020, 2022, and 2023 were evaluated against Class II water quality standards per Indonesian Government Regulation No. 22 of 2021. The assessment of WQI was determined using the National Sanitation Foundation Water Quality Index (NSF-WQI) technique revealing significant fluctuations and trends across various stations over the 2019-2023. In 2019, the water quality at Kesenden, Sukalila, and Kalijaga stations was recorded at 52.21, 56.40, and 53.36, respectively. By 2020, began of COVID 19, there was a noticeable decreasing of WQI, Sukalila sustained a "Moderate" classification with a WQI of 54.59, whereas Kesenden and Kalijaga witnessed declines with values recorded at 49.5 and 49.7, respectively. However, the peak-implementation of the CARE program in 2022 saw a drastic decline in water quality, with values dropping below the threshold in all observed stations, 23.97 in Kesenden, 23.10 in Sukalila, and 35.36 in Kalijaga. Meanwhile, the water quality in 2023 experienced increasing (remained in the poor category) with index values of 44.31, 35.14, and 42.0 at Kesenden, Sukalila, and Kalijaga, respectively. The findings underscore the complex interplay between human activities and environmental health, highlighting the need for sustainable practices and robust water management policies to mitigate the adverse effects of such disruptions. The results from the monitoring of ocean health pre- and post-the CARE implementation in the pandemic era have provided a unique opportunity to reflect on human behavior and its impact on the environment, emphasizing the importance of adopting pro-environmental behaviors to support sustainable development in the post-pandemic era. PRACTITIONER POINTS: The onset of the COVID-19 pandemic led to an improvement in water quality due to the reduction in industrial and human activities resulting CARE. The significant reduction in anthropogenic activities such as industry and transportation, which lead the improvement in DO, pH, and coliform because decreasing the phosphate, nitrate, turbidity, total solid, and BOD. The CARE program in 2022 and 2023, there was a marked decline in the water quality index across all monitoring stations in Cirebon. CARE period of reduced anthropogenic pressure offers valuable insights for policymakers to develop sustainable water management strategies to maintain and further improve water quality post-pandemic., (© 2025 Water Environment Federation.)

Zooplankton play a crucial role in estuarine ecosystems by aiding nutrient cycling through trophic chains and contributing to large-scale water filtration. The present review highlights the zooplankton research conducted over the last decade (2014-2024) in the Indian Sundarbans, with a focus on research trends, species distribution, hydrological associations, and long-term monitoring and conservation strategies. The study reveals a surge in zooplankton research after 2019, with an emphasis on both small- and large-scale studies. However, tidal creek/canals remain less explored compared to rivers. A lack of methodological standardization in zooplankton research is evident across the Indian Sundarbans. The Saptamukhi-Thakuran-Matla river stretch exhibited the highest species diversity, with 70 species recorded. Similarly, the tidal creeks and canals of Sagar Island were identified as species-rich habitats, with 63 species reported. Oithona brevicornis was found in seven riverine stretches, while Paracalanus parvus and Labidocera euchaeta were each recorded from six rivers, but Bestiolina similis was mostly reported as the numerically predominant zooplankton species. Salinity emerged as the most influential hydrological factor for zooplankton distribution, followed by dissolved oxygen and water temperature. However, increasing pollution, climate change-induced cyclones, salinization, and human activities are threatening zooplankton communities of the Indian Sundarbans. Furthermore, the review underscores the need for long-term monitoring strategies in the Sundarbans, by addressing the integration of remote sensing method, automated devices, data repositories, and ecological modeling approaches. Additionally, the present review recommends future policies for zooplankton conservation, emphasizing habitat protection, water quality assessment, stakeholder engagement, and securing funding to implement long-term monitoring initiatives., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Although studies have previously investigated metabolic disruptions in the peripheral nervous system (PNS), the exact metabolic mechanisms underlying DPN remain largely unknown. Herein, a specific form of metabolic remodeling involving aberrant ketogenesis within Schwann cells (SCs) in streptozotocin (STZ)-induced type I diabetes mellitus is identified. The PNS adapts poorly to such aberrant ketogenesis, resulting in disrupted energy metabolism, mitochondrial damage, and homeostatic decompensation, ultimately contributing to DPN. Additionally, the maladaptive peripheral ketogenesis is highly dependent on the cannabinoid type-1 receptor (CB 1 R)-Hmgcs2 axis. Silencing CB 1 R reprogrammed the metabolism of SCs by blocking maladaptive ketogenesis, resulting in rebalanced energy metabolism, reduced histopathological changes, and improved neuropathic symptoms. Moreover, this metabolic reprogramming can be induced pharmacologically using JD5037, a peripheral CB 1 R blocker. These findings revealed a new metabolic mechanism underlying DPN, and promoted CB 1 R as a promising therapeutic target for DPN., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Current early cancer diagnostic technologies, such as imaging, molecular tests, endoscopic techniques, and biopsies, face considerable challenges in low-and middle-income countries (LMICs) due to high costs, procedural complexity, and limited resource access. Microneedle-based liquid biopsy for skin interstitial fluid (ISF) offers a practical and minimally invasive alternative for cancer diagnosis in these settings. This review systematically examines ISF liquid biopsy methods for their effectiveness in capturing cancer biomarkers directly from the skin and assesses their potential to address diagnostic needs in low-resource environments. Recent innovations in microneedle design and ISF underscore their potential in enabling early, accessible cancer detection tailored to LMICs' needs. Additionally, integrating artificial intelligence (AI) for data interpretation is proposed as a way to enhance diagnostic accuracy and enable real-time point-of-care (POC) applications. Collectively, these advances illustrate a flexible, scalable model for accessible cancer diagnostics, with significant implications for improving early detection and healthcare quality in resource-limited environments., (© 2025 Wiley‐VCH GmbH.)

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections. We analyzed 689 digitized H&Es of pure primary DCIS of which 226 were diagnosed with subsequent iIBC and 463 were not. The distribution of 15 duct morphological measurements was summarized in 55 morphometric variables. A ridge regression classifier with cross validation predicted 5-years-free of iIBC with an area-under the curve of 0.67 (95% CI 0.57-0.77). A combined clinical-morphometric signature, characterized by small-sized ducts, a low number of cells and a low DCIS/stroma ratio, was associated with outcome (HR = 0.56; 95% CI 0.28-0.78). AIDmap has potential to identify harmless DCIS that may not need treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Hypothalamic hamartomas (HHs) are associated with pharmacoresistant epilepsy. Stereotactic radiofrequency thermocoagulation (SRT) shows promise as a disconnecting intervention. Although magnetic resonance imaging (MRI) is typically used to determine the attachment and intervention side, it presents challenges in cases of bilaterally attached HH, where the epileptogenic side is unclear. The lateralizing potential of electroclinical parameters in such cases remains uncertain. This retrospective study evaluates the lateralization value of specific parameters, particularly in patients with unilateral HH, to improve future diagnostics and treatment approaches for bilateral HH., Methods: Four lateralizing parameters-semiology, ictal electroencephalography (EEG), and interictal epileptiform discharges during awake (IEDs w ) and sleep states (IEDs s )-were assessed for correlation with HH attachment side using Spearman's ρ. We calculated areas under the curves (AUCs) and cutoffs for left and right IED s prognostic lateralizing value, plotting differences between IED sright and IED sleft in a receiver-operating characteristic(ROC) curve to establish the required preponderance of unilateral IEDs s to differentiate between left and right HHs. Binomial logistic regression was employed to predict the HH attachment side., Results: We included 25 patients (2-55 years of age) with mainly unilateral (n = 22) HHs who underwent SRT and presurgical evaluation. All parameters correlated with HH attachment side (semiology R = -.62, p = .005; ictal EEG R = .51, p = .047; IED s R = .55, p = .018; IED w , R = .61, p = .018). AUC values for right and left IED s were .76 (p = .047) and .85 (p = .019), respectively, with cutoffs of .34 and .15. The AUC for "IED sright -IED sleft " was .98 (p = .0018) with a cutoff of .16. IEDs s and semiology were significant predictors, achieving 88% correct lateralization., Significance: IEDs s are promising biomarkers for HH lateralization in unilateral HH. The predominance of unilateral IEDs s suggests ipsilateral HH. Even in cases with predominantly bilateral IEDs s , a slight preponderance of unilateral IEDs s can indicate the attachment side. In addition, combining IEDs s and semiology provides a predictive model for HH lateralization., (© 2025 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al., p. 16 See related article by Stratton et al., p. 22 See related article by Goodwin et al., p. 34., (©2025 American Association for Cancer Research.)

Background and Aim: Pancreatic and hepatobiliary cancers are increasing in prevalence and contribute significantly to cancer-related mortality worldwide. Emerging therapeutic approaches, particularly immunotherapy, are gaining attention for their potential to harness the patient's immune system to combat these tumors. Understanding the role of immune cells in the tumor microenvironment (TME) and their metabolic reprogramming is key to developing more effective treatment strategies. This review aims to explore the relationship between immune cell function and glucose metabolism in the TME of pancreatic and hepatobiliary cancers., Methods: This review synthesizes current research on the metabolic adaptations of immune cells, specifically focusing on glucose metabolism within the TME of pancreatic and hepatobiliary cancers. We examine the mechanisms by which immune cells influence tumor progression through metabolic reprogramming and how these interactions can be targeted for therapeutic purposes., Results: Immune cells in the TME undergo significant metabolic changes, with glucose metabolism playing a central role in modulating immune responses. These metabolic shifts not only affect immune cell function but also influence tumor behavior and progression. The unique metabolic features of immune cells in pancreatic and hepatobiliary cancers provide new opportunities for targeting immune responses to combat these malignancies more effectively., Conclusion: Understanding the complex relationship between immune cell glucose metabolism and tumor progression in the TME of pancreatic and hepatobiliary cancers offers promising therapeutic strategies. By modulating immune responses through targeted metabolic interventions, it may be possible to improve the efficacy of immunotherapies and better combat these aggressive cancers., (© 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aromatase deficiency (ORPHA:91; OMIM: 613,546) is a rare, autosomal recessive disorder due to loss of function mutations in the CYP19A1 gene, described in both genders with an estimated incidence below 1/1000000. While in female the clinical manifestations generally occur at birth or in early infancy, and mainly involve sexual characteristics, in men clinical signs of aromatase deficiency mostly occur in puberty and especially in late puberty, so that diagnosis is generally established after the second decade due to tall stature, unfused epiphyses and reduced bone mass. Here we review the available information concerning the skeletal and extraskeletal phenotype and the clinical management of bone health in patients with aromatase CYP19A1 gene mutations., Competing Interests: Declarations. Conflict of interest: All the authors have no conflict of interest to declare for this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Melanoma has emerged as a significant threat to human life and health. Microneedle (MN)-mediated transdermal drug delivery (TDD) has garnered attention in melanoma treatment for bypassing the first-pass effect. However, the propensity of melanoma to metastasize presents substantial challenges for MN mediated local treatment. Developing systemic therapies, such as immunotherapy in combination with TDD, is crucial for achieving effective melanoma treatment. Herein, a polyvinyl alcohol (PVA) MN-mediated multifunctional TDD system, designated MN@PDA@1-MT/CUR/DOX@HA (MN@PMCDH), was developed for synergetic chemotherapy/photothermal/immunotherapy of melanoma. PMCDH nanomedicines penetrate deep skin layers through MNs, accumulate at tumor sites guided by hyaluronic acid (HA), and selectively release drugs in response to the acidic tumor microenvironment and near-infrared (NIR) stimulation. Released curcumin (CUR) significantly enhances the efficacy of photothermal therapy (PTT) and chemotherapy, as well as improves the induction of immunogenic cell death (ICD) by increasing melanoma sensitivity to polydopamine (PDA)-mediated photothermal effects and doxorubicin (DOX). Moreover, the incorporation of 1-methyltryptophan (1-MT) to reverse the tumor immunosuppressive microenvironment can further enhance the effects of immunotherapy. In vitro studies revealed that the MN@PMCDH system can effectively induce ICD and inhibit tumor cell growth. Additionally, remarkable deep tumor cell inhibition effects are also achieved in 3D tumor models., (© 2024 Wiley-VCH GmbH.)

Cancer immunotherapy has emerged as one of the most promising modalities for cancer treatment providing hopes of cancer patients with the significant advantages over traditional antitumor therapy methods. Supramolecular assemblies based on host-guest interactions have been widely explored in the field of cancer immunotherapy as the delivery systems. A variety of supramolecular materials show unique features for efficient drug encapsulation, targeting delivery and release, which are favorable to activate antitumor immune responses especially through combination of different treatment strategies. In this review article, we summarize the research progresses of supramolecular assemblies via host-guest interactions for tumor immunotherapy. The construction of various drug delivery systems including hydrogels, liposomes, and polymeric nanoparticles, the drug encapsulation and delivery, as well as advantages and disadvantages are discussed. The perspectives related to future developments in this field are also described., (© 2024 Wiley-VCH GmbH.)

Background: Three-dimensional printing (3D printing) technology and computer navigation technology have been gradually applied in surgeries for orbital blowout fractures. This study compared the efficacy of traditional techniques (group I) and 3D printing combined with computer navigation technology-assisted techniques (group II) in the management of orbital blowout fractures., Methods: All patients treated for orbital blowout fractures in the Affiliated Hospital of Yangzhou University from March 2018 to February 2021 were reviewed. The primary predictive variable was surgical techniques used for orbital fractures (traditional techniques or 3D printing combined with computer navigation technology-assisted techniques). Outcome variables included diplopia, limitation of extraocular muscle movement, and enophthalmos orbital volume., Results: All the surgeries were successfully performed without serious complications. Six months after the operation, the degree of diplopia and limitation of extraocular muscle movement in the traditional techniques group and 3D printing combined with computer navigation technology-assisted techniques group were significantly improved (the former Z = -2.670, P =0.008, the latter Z =-3.584, P <0.001 and the former Z =-4.852, P <0.001, the latter Z =-5.427, P <0.001, respectively). There were no significant differences in the degree of diplopia and limitation of extraocular muscle movement between the 2 groups before the operation (the former Z =-0.842, P =0.400; the latter Z =-0.567, P =0.571), and there were significant differences after the operation (the former Z =-2.773, P =0.006; the latter Z =-2.892, P =0.004), and the 3D printing combined with computer navigation technology-assisted techniques group showed an advantage over the traditional techniques group. The difference in bilateral enophthalmos and orbital volume in traditional techniques groups and 3D printing combined with computer navigation technology-assisted techniques groups was dramatically decreased (the former t =12.558, P <0.001, the latter t =12.659, P <0.001, and the former t =19.194, P <0.001, the latter t =17.770, P <0.001, respectively). There were no significant differences in bilateral enophthalmos and orbital volume between the 2 groups before the operation (the former t =-0.410, P =0.683; the latter t =0.311, P =0.756), and there were significant differences after the operation (the former t =4.081, P <0.001; the latter t =4.078, P <0.001). There were statistically significant differences in surgical time and cost between the traditional technology group and the 3D printing combined with computer navigation technology-assisted technology group (the former t =8.445, P <0.001, and the latter t =3.534, P <0.001); 3D printing combined with computer navigation technology-assisted techniques group spent more surgical time and money than the traditional techniques group., Conclusions: The application of 3D printing combined with computer navigation techniques in the management of orbital blowout fractures can significantly improve the accuracy and safety of the operation. 3D printing combined with computer navigation technology-assisted techniques group spent more surgical time and money., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Recent research has exposed a growing body of proof underscoring the importance of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in maintaining the physical composition of neurons and influencing cognitive functioning in both standard and atypical circumstances. Extensive research has been conducted on the possible application of miRNAs and lncRNAs as biomarkers for various diseases, with a particular focus on brain disorders, as they possess remarkable durability in cell-free surroundings and can endure repeated freezing and thawing processes. It is intriguing to note that miRNAs and lncRNAs have the ability to function through paracrine mechanisms, thereby playing a role in communication between different organs. Recent research has proposed that the improvement of cognitive abilities through physical exercise in mentally healthy individuals is a valuable method for uncovering potential connections between miRNAs, or microRNAs, and lncRNAs, and human cognitive function. The process of cross-correlating data from disease models and patients with existing data will be crucial in identifying essential miRNAs and lncRNAs, which can potentially act as biomarkers or drug targets in the treatment of cognitive disorders. By combining this method with additional research in animal models, we can determine the function of these molecules and their potential impact on therapy. This article discusses the latest research about the primary miRNAs, lncRNAs, and their exosomes that are affected by physical activity in terms of human cognitive function., Competing Interests: Declarations. Ethics Approval and Consent to Participate: None. Consent for Publication: None. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dioscorea alata, a key tuber crop for global food security, is threatened by anthracnose disease caused by Colletotrichum gloeosporioides. However, identification of functional resistance genes against C. gloeosporioides in D. alata is challenging due to low flowering and hybridization efficiency of this plant. Nucleotide-binding leucine-rich repeat (NLR) genes constitute the largest group of plant disease resistance genes, from which functional genes against diverse pathogens across various crops have been cloned. In this study, a comprehensive genome-wide analysis identified 346 NLR genes from D. alata, including one RNL and 345 CNLs. These NLRs were unequally distributed on 20 chromosomes, with chromosome 3 harboring the highest number (78 NLR genes). The majority of NLR genes (91%) were located in multigene clusters, implying that tandem or proximal duplication was the primary driving force for NLR gene expansion in D. alata. Comparative analysis of Dioscoreaceae species revealed high variability and differential expansion patterns of NLR genes. In addition, transcriptome profiling of D. alata post-infection with C. gloeosporioides identified 12 differentially expressed NLR genes. In summary, this study sheds new light on the genetic architecture and evolutionary dynamics of D. alata NLR genes, offering valuable insights for cloning functional genes against C. gloeosporioides., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The global burden of cancer as a major cause of death and invalidity has been constantly increasing in the past decades. Monoamine oxidases (MAO) with two isoforms, MAO-A and MAO-B, are mammalian mitochondrial enzymes responsible for the oxidative deamination of neurotransmitters and amines in the central nervous system and peripheral tissues with the constant generation of hydrogen peroxide as the main deleterious ancillary product. However, given the complexity of cancer biology, MAO involvement in tumorigenesis is multifaceted with different tumors displaying either an increased or decreased MAO profile. MAO inhibitors are currently approved for the treatment of neurodegenerative diseases (mainly, Parkinson's disease) and as secondary/adjunctive therapeutic options for the treatment of major depression. Herein, we review the literature characterizing MAO's involvement and the putative role of MAO inhibitors in several malignancies, and also provide perspectives regarding the potential biomarker role that MAO could play in the future in oncology., Competing Interests: Declarations. Conflict of interest: Danina M. Muntean is an Associate Editor at Molecular and Cellular Biochemistry. Adrian Sturza is a member of the Editorial Board of the same journal. Apart from the above-mentioned statements, the authors have no relevant financial or non-financial interests to disclose. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. The Author(s).)

In Salmonella Typhimurium, efflux pump proteins, such as AcrD actively expel drugs and hazardous chemicals from bacterial cells, resulting in treatment failure and the emergence of antibiotic-resistant variants. Focusing on AcrD may lead to the development of novel antimicrobials against multidrug-resistant bacteria. However, challenges persist in achieving high selectivity, low toxicity, and effective bacterial penetration. Natural products, particularly microbial secondary metabolites, possess distinct chemical structures that may target the efflux pump systems. The efflux pump inhibitor capabilities of Fusarium nygamai compounds in Salmonella have not been previously investigated. This study employed molecular docking and molecular dynamics simulations to evaluate 25 F. nygamai compounds as potential inhibitors of AcrD. Additionally, the pharmacological characteristics of these substances were examined. Molecular docking results revealed that 3,6-Dimethoxy-2,5-dinitrobenzonitrile, methyl (2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate, and 7-Methyl-5-nitro-1,4-dihydro-quinoxaline-2,3-dione exhibited the highest binding energies with AcrD. Furthermore, molecular dynamics simulations indicated stable ligand-receptor complex variations over time. This study contributes to the efforts against antibiotic resistance and the improvement of Salmonella infection treatment outcomes globally by facilitating the development of novel therapeutic approaches and enhancing antibiotic efficacy., Competing Interests: Declarations. Conflicts of interest: The authors declare no potential conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Collagen as the main structural component of the cornea exhibits unique and highly organized fibril lamellae, which contribute to the maintenance of corneal structure and transparency. Nevertheless, collagen assembly in vitro to create ideal artificial corneal substitutes with human cornea comparable thickness and optics is still limited. Here, glycerol as a regulator can reconcile collagen thickness, transparency, and permeability, a conflicting goal by current keratoprosthesis strategies. Structure analysis reveals that glycerol treatment induces collagen hydrogels to undergo a sequential three-step multiscale structural evolution: weakened collagen crystallization at the molecular level, followed by ordered and distanced microfibril packaging at the nanoscale, and ultimately lamellar structure as well as fibril diameter and spacing-dependent optics at a macroscopic level. Such ultrastructure is then stabilized by oxazolidine crosslinking to obtain a collagen-based artificial corneal substitute (Col-Gly-OX) with optimal integration of optical clarity, mechanical robustness, high permeability, manufacturability, easy preservation and in vitro biocompatibility. Further in vivo study demonstrates that Col-Gly-OX displays excellent tissue integration, epithelialization, and stromal remodeling in a rabbit lamellar keratectomy. Overall, this work illustrates the potential of glycerol regulator to mediate the multiscale structural organization of collagen, providing a green, simple and effective strategy for the development of bionic artificial cornea., (© 2024 Wiley‐VCH GmbH.)

Highly arylated propeller-shaped heteroarenes constitute an intriguing class of molecular scaffolds for material science applications. Among these, tetraarylated furans demonstrate differentiated properties as compared to other similar heterocyclic cores. The synthetic complexity to access tetraarylated furans increases significantly with increasing number of different peripheral aryl groups. There are only a very limited number of methodologies available to access furans with four different (hetero)aryl substituents. Notably, none of these involve direct oxidative coupling on the furan core as the method of choice. Herein, we report the first methodology based on a sequential two-fold oxidative C-C coupling of furans with indoles to access bis(indolyl)furans (BIFs) - a new class of 'extremely congested' tetra-(hetero)arylated furans with up to four different substituents. The reaction is mediated by inexpensive, earth-abundant FeCl 3 ⋅6H 2 O and displays high efficiency, wide substrate scope, modularity and aqueous compatibility. Moreover, we also present the first validation of the distinct aggregation-caused quenching (ACQ) property of the tetraarylated furans beyond only phenyls as peripheral groups and disclose new mechanistic underpinnings for the same., (© 2024 Wiley-VCH GmbH.)

Objective: This study was undertaken to anatomically categorize insulo-opercular focal cortical dysplasia (FCD) lesions according to their location and extent, and to summarize corresponding stereoelectroencephalographic (SEEG) patterns to guide preoperative evaluation and surgical planning., Methods: Patients who underwent epilepsy surgery for insulo-opercular FCD between 2015 and 2022 were enrolled. FCD lesions were categorized into insular, peri-insular, opercular, and complex types based on their location and extent, as ascertained from electroclinical and neuroimaging data. SEEG signals from the seizure onset electrodes were collected for quantitative analysis. The normalized interictal spike counts, high-frequency oscillation (HFO) counts, and ictal epileptogenicity index (EI) values of the insular and opercular channels were calculated. The spatial patterns of the spike counts, HFO counts, and EI values were analyzed. Cluster analyses utilizing spike counts, HFO counts, and EI values were performed for automatic categorization, and the results were compared with the manual categorization from the preoperative evaluations., Results: A total of 53 patients were included, comprising 10 insular, 17 peri-insular, 24 opercular, and two complex cases. Thirty-eight patients were included in the quantitative SEEG analysis. Spike, HFO, and EI analyses indicated that in insular FCDs, the values of the three parameters were higher in insular channels than in opercular channels. In peri-insular FCDs, the values in insular and opercular channels were comparable, whereas in opercular FCDs, the values were higher in opercular channels than in insular channels. The accuracies of the cluster analysis based on the spike counts, HFO counts, and EI values were 71.05% (27/38), 76.32% (29/38), and 86.84% (33/38), respectively. Surgical strategies were proposed according to the anatomical categorization, achieving a favorable postoperative seizure-free rate of 84.91%., Significance: Insulo-opercular FCDs can be categorized into insular, peri-insular, opercular, and complex types. SEEG patterns can facilitate the automatic categorization of insulo-opercular FCDs, thereby enhancing preoperative planning and surgical outcomes., (© 2024 International League Against Epilepsy.)

This study presents a Ni-photoredox method for indole N-arylation, broadening the range of substrates to include indoles with unprotected C3-positions and base-sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni-catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni-photoredox carbon-heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre-coordination of indole renders a more electron-rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron-rich aryl bromide substrates. Thus, this work highlights the often-overlooked influence of X-type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni-photoredox C-heteroatom couplings., (© 2024 Wiley-VCH GmbH.)

Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT., Competing Interests: Declarations. Conflict of interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, has been shown to be effective for patients with ALK-positive non-small cell lung cancer (NSCLC). However, alectinib resistance is a serious problem worldwide. To the best of our knowledge, little information is available on its molecular mechanisms using the Gene Expression Omnibus (GEO) database. In this study, the differentially expressed genes (DEGs) were selected from the gene expression profile GSE73167 between parental and alectinib-resistant human lung adenocarcinoma (LUAD) cell samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). The construction of protein-protein interaction (PPI) network was performed to visualize DEGs. The hub genes were extracted based on the analysis of the PPI network using plug-in cytoHubba of Cytoscape software. The functional roles of the key genes were investigated using Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer (UALCAN), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Estimation Resource (TIMER) analysis. The networks of kinase, miRNA, and transcription-factor targets of SFTPD were explored using LinkedOmics. The drug sensitivity analysis of SFTPD was analyzed using the RNAactDrug database. Results showed a total of 144 DEGs were identified. Five hub genes were extracted, including mucin 5B (MUC5B), surfactant protein D (SFTPD), deleted in malignant brain tumors 1 (DMBT1), surfactant protein A2 (SFTPA2), and trefoil factor 3 (TFF3). The survival analysis using GEPIA displayed that low expression of SFTPD had a significantly negative effect on the prognosis of patients with LUAD. GSEA revealed that low expression of SFTPD was positively correlated with the pathways associated with drug resistance, such as DNA replication, cell cycle, drug metabolism, and DNA damage repair, including mismatch repair (MMR), base excision repair (BER), homologous recombination (HR), and nucleotide excision repair (NER). The SFTPD expression was negatively correlated with the drug sensitivity of alectinib according to RNAactDrug database. The expression of SFTPD was further validated in parental H3122 cells and alectinib-resistant H3122 cells by quantitative reverse transcription PCR (RT-qPCR). In conclusion, our study found that the five hub genes, especially low expression of SFTPD, are closely related to alectinib resistance in patients with LUAD., Competing Interests: Declarations Competing interests NM, DBL, and DLW are employees of ChosenMed Technology. The remaining authors declare that they have no conflicts of interest. Ethical Approval and Consent to Participate Not applicable (GEO is an open database with ethical permission obtained for patients who participated. The data can be downloaded for free for research and publication. Open-source data are used in our research, so there are no ethical concerns). Consent for Publication Not applicable., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Semi-interpenetrating polymer networks (SIPNs) have garnered significant interest due to their potential applications in self-healing materials, drug delivery systems, electrolytes, functional membranes, smart gels and, toughing. SIPNs combine the characteristics of physical cross-linking with advantageous chemical properties, offering broad application prospects in materials science and engineering. This perspective introduces the history of semi-interpenetrating polymer networks and their diverse applications. Additionally, the ongoing challenges associated with traditional semi-interpenetrating polymer materials are discussed and provide an outlook on future advancements in novel functional SIPNs., (© 2024 Wiley‐VCH GmbH.)

Tissue-culture-ware polystyrene is the gold standard for in vitro cell culture. While microengineering techniques can create advanced cell microenvironments in polystyrene, they require specialized equipment and reagents, which hinder their accessibility for most biological researchers. An economical and easily accessible method is developed and validated for fabricating microstructures directly in polystyrene with sizes approaching subcellular dimensions while requiring minimal processing time. The process involves deep ultraviolet irradiation through a shadow mask or ink pattern using inexpensive, handheld devices followed by selective chemical development with common reagents to generate micropatterns with depths/heights between 5 and 10 µm, which can be used to guide cell behavior. The remarkable straightforwardness of the process enables this class of microengineering techniques to be broadly accessible to diverse research communities., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

This study presents an acetylene gas sensor capable of in situ monitoring transformer oils. This sensor utilizes carbon nanotubes (CNTs) embedded in polyimide (PI) synthesized by floating catalyst chemical vapor deposition. Unlike conventional sensors that target hydrocarbon gases dissolved in oil and measure the gas extracted from the oil, the proposed CNT-PI sensor detects gas within the oil in real time. The PI embedding technique effectively anchors and shields the CNT network against fluidic damage, ensuring stable sensing performance over 6 months, even under friction stress caused by oil convection. Decorating CNTs with gold nanoparticles further enhances the sensitivity and response of the sensor. The sensor achieves a high response (10.5% at 30 ppm) and fast response/recovery times (28 s/77 s), Furthermore, the sensor demonstrates good response (10.4% at 30 ppm) and moderate response/recovery times (444 s/670 s) in an oil medium, which qualifies for industrial applications. Additionally, a CNT-PI-based heater is integrated into the sensor as a multilayer component, maintaining an optimal operating temperature of 90 °C. The CNT-PI sensor demonstrates consistent gas-sensing performance even after 10,000 bending cycles and exhibits superior characteristics, indicating its compatibility with various forms of transformers., (© 2024 Wiley‐VCH GmbH.)

Surface functionalization and the combined utilization of zero-dimensional and two-dimensional nanomaterials is an effective method to achieve highly sensitive detection for electrochemical analysis. Using an all-in-one strategy, phthalocyanine, gold nanoparticles, and ionic liquid were successively modified on the graphene surface as a highly integrated electrode modification material. Phthalocyanine can repair the defects of reduced graphene oxide by binding to the graphene structure surface through non-covalent functionalization. The combination of ionic liquid on the surface of gold nanoparticles can enhance their physical and chemical activity while preserving their stability. The obtained phthalocyanine-coated graphene nanosheets decorated with ionic liquid-functionalized gold nanoparticles nanocomposites had enhanced electrocatalysis and conductivity ability, and were used for highly sensitive electrochemical detection of ascorbic acid in fruit juices. Excellent results were obtained for the detection of ascorbic acid in the linear range 0.05 to 50 µmol/L with a detection limit of 6.80 nmol/L (S/N = 3) and a sensitivity of 2.68 μA μM -1  cm -2 , indicated that the proposed sensor strategy with multiple signal amplification can achieve higher detection sensitivity. Furthermore, the sensor was used to quantify ascorbic acid content in grapefruit and orange juice with good selectivity and accuracy. The highly integrated electroactive nanocomposites construction method described may also be used with other electrode modification materials and is anticipated to yield fresh perspectives on the advancement of ultrasensitive detection., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Phosphodiesterase enzyme 5 (PDE5) inhibitors have emerged as one of the leading molecules for the treatment of erectile dysfunction (ED). PDE5 inhibitors are categorized structurally into several classes. PDE5 inhibitors have been a multidisciplinary endeavor that attracts the attention of researchers because of their multiple pharmaceutical applications. Beyond their action on ED, PDE5 inhibitors are widely used in treatment of benign prostatic hypertrophy (BPH), Eisenmenger's syndrome, Raynaud's Disease, Intrauterine growth retardation (IUGR), Mountain sickness, Bladder pain syndrome/interstitial cystitis (BPS/IC), pulmonary arterial hypertension and type II diabetes (insulin resistance). In addition, PDE5 inhibitors also show promising antiproliferative activity, anti-Alzheimer and COX-1/COX-2 inhibitory activity (anti-inflammatory). Pharmacokinetics, Pharmacogenetics and toxicity of PDE5 inhibitors were finally explored. The diverse therapeutic applications, the high feasibility of structural modification and the appropriate pharmacokinetic properties of PDE5 inhibitors have motivated researchers to develop new scaffolds that have been either under clinical trials or approved by FDA and utilize them to overcome some recent global concerns, such as COVID-19., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

The toxic impact of environmentally relevant nominal sub-lethal concentration of lead nitrate (23 mg/L) on the gills of Cyprinus carpio after 30 days of exposure was assessed. Structural alterations were analyzed through histopathology, and the DNA damage rate in peripheral erythrocytes was evaluated by alkaline comet assay. A significant deviation in the gill histoarchitecture was observed compared to the control group. Significant changes, including the curling of secondary lamellae, loss of filaments, necrosis, hyperplasia, hypertrophy of cells of primary filament, and vacuolization, were found in the fish exposed to nominal sub-lethal concentration of lead nitrate. Moreover, the comet assay showed lead nitrate-induced DNA damage, evidenced by the length of the DNA "tail" in the exposed fish. The findings of this study strongly indicated that lead nitrate, even at sub-lethal levels, could significantly alter the overall physiology of the fish. This situation could lead to severe ecological consequences., (© 2024 The Author(s). Microscopy Research and Technique published by Wiley Periodicals LLC.)

Non-volatile memristors dynamically switch between high (HRS) and low resistance states (LRS) in response to electrical stimuli, essential for electronic memories, neuromorphic computing, and artificial intelligence. High-entropy Prussian blue analogs (HE-PBAs) are promising insertion-type battery materials due to their diverse composition, high structural integrity, and favorable ionic conductivity. This work proposes a non-volatile, bipolar memristor based on HE-PBA. The device, featuring an active layer of HE-PBA sandwiched between Ag and ITO electrodes, is fabricated by inkjet printing and microplotting. The conduction mechanism of the Ag/HE-PBA/ITO device is systematically investigated. The results indicate that the transition between HRS and LRS is driven by an insulating-metallic transition, triggered by extraction/insertion of highly mobile Na + ions upon application of an electric field. The memristor operates through a low-energy process akin to Na + shuttling in Na-ion batteries rather than depending on formation/rupture of Ag filaments. Notably, it showcases promising characteristics, including non-volatility, self-compliance, and forming-free behavior, and further exhibits low operation voltage (V SET = -0.26 V, V RESET = 0.36 V), low power consumption (P SET = 26 µW, P RESET = 8.0 µW), and a high R OFF /R ON ratio of 10 4 . This underscores the potential of high-entropy insertion materials for developing printed memristors with distinct operation mechanisms., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Chickpea is a major source of proteins and is considered the most economically vital food legume. Chickpea production is threatened by several abiotic and biotic factors worldwide. The main constraints limiting worldwide chickpea production are abiotic conditions such as drought, heat, salinity, and cold. It is clear that chickpea is treasured for its nutritive value, in particular its high protein content, and hence study of problems like drought, cold and salinity stresses are very important concerning chickpeas. In this regard, several physiological, biochemical, and molecular mechanisms are reviewed to confer tolerance to abiotic stress. The most crippling economic losses in agriculture occur due to these abiotic stressors, which affect plants in many ways. All these abiotic stresses affect the water relations of the plant, both at the cellular level as well as the whole-plant level, causing both specific and non-specific reactions, damage and adaptation reactions. These stresses share common features. Breeding programs use a huge collection of over 100,000 chickpea accessions as their foundation. Significant advancements in conventional breeding, including mutagenesis, gene/allele introgression, and germplasm introduction, have been made through this method. Abiotic tolerance and yield component selection are made easier by creating unique DNA markers for the genus Cicer, which has been made possible by developments in high-throughput sequencing and molecular biology. Transcriptomics, proteomics, and metabolomics have also made it possible to identify particular genes, proteins, and metabolites linked to chickpea tolerance to abiotic stress. Chickpea abiotic stress tolerance has been directly and potentially improved by biotechnological applications, which are covered by all 'Omics' approaches. It requires information on the abiotic stress response at the different molecular levels, which comprises gene expression analysis for metabolites or proteins and its impact on phenotype. Studies on chickpea genome-wide expression profiling have been conducted to determine important candidate genes and their regulatory networks for abiotic stress response. This study aimed to offer a detailed overview of the diverse 'Omics' approaches for resilience's to abiotic stresses on chickpea plants., Competing Interests: Declarations Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

High-entropy alloys (HEAs) have emerged as burgeoning heterogeneous catalysts due to their vast material space, unique structure, and superior stability. However, the dominant trial-and-error approaches hamper the exploration of efficient catalysts, necessitating the development of rational design strategies. Here, we report a progressive approach to the design and fabrication of HEA catalysts guided by alloying effects toward propane dehydrogenation. Cu, Sn, Au, and Pd are selected and demonstrated to induce dilution, encapsulation, surface enrichment, and inhomogeneity effects on Pt. The fabricated HEA, PtCuSnAuPd/SiO 2 , exhibits excellent activity, selectivity, and stability. The propylene formation rates reach 256 and 390 mol C3H6 g Pt -1  h -1 at 550 and 600 °C, respectively. Systematic characterizations reveal that the random elemental mixing, structural stability, and high Pt exposure promote the exposure of abundant stable isolated Pt sites. This work comprehensively explores the rational design and fabrication of HEA catalysts from a unique perspective, offering opportunities for developing advanced catalysts., (© 2024 Wiley-VCH GmbH.)

The reaction between aldehydes or ketones and alkynes-the carbonyl-alkyne metathesis-constitutes a very useful strategy for the synthesis of α,β-unsaturated carbonyls. We now demonstrate that iodine is a highly efficient catalyst for both the intra- and intermolecular metathesis reaction in very small concentrations (0.1-1 mol %). Our protocol outperforms other catalytic systems, is operationally very simple, cheap, metal-free, and tolerates a large variety of functional groups (e. g., -CN, -CO 2 Me, -Br, -OH) at very low catalyst loadings. We can furthermore show that iodine-catalyzed carbonyl-alkyne metatheses can be combined with other iodine-catalyzed reactions in one-pot procedures to afford larger and more complex molecular structures. Finally, our mechanistic studies indicate that the iodonium ion is the active catalyst under the reaction conditions., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The wet-chemical synthesis of 3D confined antimony nanoparticles (Sb-NP) at low and high temperatures is described. Using reaction conditions that are mild in temperature and strong in reducing power allows the synthesis of amorphous Sb-NP stabilized with organic ligands. Exchanging the organic ligand 1-octanethiol by iodide enabled to investigate the unusual strong stability of this metastable material through simultaneous thermal analysis combining differential scanning calorimetry and thermogravimetric analysis. Additionally, in situ high temperature powder x-ray diffraction (p-XRD) shows a significant increase in stabilization of the amorphous phase in comparison to thin layered, 1D confined Sb or bulk material. Further, it is shown with scattering-type scanning near-field optical microscopy (s-SNOM) experiments that the optical response of the different phases in Sb-NP make the distinctness of each phase possible. It is proposed that the Sb-NP introduced here can serve as a 3D-confined optically addressable nanomaterial of miniaturized phase change memory devices., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABA A Rs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABA A Rs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity., (© 2024. The Author(s).)

Natural-derived biomaterials can be used as substrates for the growth, proliferation, and differentiation of cells. In this study, bovine vitreous humor as a biological material was cross-linked to silk fibroin with different concentration ratios to design a suitable substrate for corneal tissue regeneration. The cross-linked samples were evaluated with different analyses such as structural, physical (optical, swelling, and degradation), mechanical, and biological (viability, cell adhesion) assays. The results showed that all samples had excellent transparency, especially those with higher silk fibroin content. Increasing the ratio of vitreous humor to silk fibroin decreased mechanical strength and increased swelling and degradation, respectively. There was no significant difference in the toxicity of the samples, and with the increase in vitreous humor ratio, adhesion and cell proliferation increased. Generally, silk fibroin with vitreous humor can provide desirable characteristics as a transparent film for corneal wound healing., (© 2024 Wiley Periodicals LLC.)

3D in vitro model has emerged as a valuable tool for studying tissue development, drug screening, and disease modeling. 3D systems can accurately replicate tissue microstructures and physiological features, mirroring the in vivo microenvironment departing from conventional 2D cell cultures. Various 3D in vitro models utilizing biomacromolecules like collagen and synthetic polymers have been developed to meet diverse research needs and address the complex challenges of contemporary research. Silk proteins, bearing structural and functional similarities to collagen, have been increasingly employed to construct advanced 3D in vitro systems, surpassing the limitations of 2D cultures. This review examines silk proteins' composition, structure, properties, and functions, elucidating their role in 3D in vitro models. Furthermore, recent advances in biomedical applications involving silk-based organoid models are discussed. In particular, the unique physiological attributes of silk matrix constituents in in vitro tissue constructs are highlighted, providing a meticulous evaluation of their importance. Additionally, it outlines the current research hurdles and complexities while contemplating future avenues, thereby paving the way for developing complex and biomimetic silk protein-based microtissues., (© 2024 Wiley‐VCH GmbH.)

The study investigates the potentials of the rapid crosslinking hydrogel concoction comprising of natural silk fibroin (SF) and recombinant tailorable collagen-like protein with binding domains for wound repair. The formation of dityrosine crosslinks between the tyrosine moieties augments the formation of stable hydrogels, in the presence of the cytocompatible photo-initiator riboflavin and visible light. This uniquely engineered PASCH (Photo-activated silk fibroin and tailor-made collagen-like protein hydrogel) confers the key advantage of improved biological properties over the control hydrogels comprising only of SF. The physico-chemical characterization of the hydrogels with respect to crosslinking, modulus, and thermal stability delineates the ascendancy of PASCH 7:3 over other combinations. Furthermore, the hybrid protein hydrogel proves to be a favorable cellular matrix as it enhances cell adhesion, elongation, growth, and proliferation in vitro. Time-lapse microscopy studies reveal an enhanced wound closure in human endothelial cell monolayer (EA.hy926), while the gene expression studies portray the dynamic interplay of cytokines and growth factors in the wound milieu facilitating the repair and regeneration of cells, sculpted by the proteins. The results demonstrate the improved physical and biological properties of fabricated PASCH, depicting their synergism, and implying their competency for use in tissue engineering applications., (© 2024 Wiley‐VCH GmbH.)

Plastic pollutants create health crises like physical damage to tissues, upset reproductive processes, altered behaviour, oxidative stress, neurological disorders, DNA damage, gene expression, and disrupt physiological functions, as the biosphere accumulates them inadvertently through the food web. Water resources have become the generic host of plastic wastes irrespective of their particle size, resulting in widespread distribution in aquatic environments. The pre-treatment step of the traditional water treatment process can easily remove coarse-sized plastic wastes. However, the fine plastic particles, with sizes ranging from nanometres to millimetres, are indifferent to the traditional water treatment. To address the escalating problems, the upgradation of different traditional physical, chemical, and biological remediation techniques offers a promising avenue for tackling tiny plastic particles from the water environment. Further, new techniques and hybrid incorporations to the existing water treatment techniques have been explored, specifically removing tiny plastic debris. A detailed understanding of the sources, fate, and impact of plastic wastes in the environment, as well as an evaluation of the above treatment techniques and their limitations and challenges, can only show the way for their upgradation, hybridization, and development of new techniques. This review paper provides a comprehensive overview of the current knowledge and techniques for the remediation of nanoplastics and microplastics., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. In this study, we used mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack-/- mice) and analyzed their behaviors in various models of pain and itch. Lbx1-Slack-/- mice exhibited increased neuropathic pain behavior after peripheral nerve injury but normal responses in a model of inflammatory pain. Unexpectedly, Lbx1-Slack-/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack-/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens., (Copyright © 2024 International Association for the Study of Pain.)

Groundwater is an essential natural resource for mankind. Due to various geogenic and anthropogenic causes, groundwater quality has raised serious concern over the years. In this study, groundwater quality was evaluated for its suitability for irrigation in the Jorhat and Golaghat Districts of Assam, India. A total of 100 groundwater samples were collected from shallow aquifers (< 35 m) from different locations during the pre-monsoon season (March-April 2022). Groundwater in the study area is slightly alkaline in nature (mean pH value of 7.44). The average cations and anions chemistry are in the order of Na +  > Ca 2+ > Mg 2+  > K + and HCO 3 -  > Cl -  > SO 4 2-  > CO 3 2- , respectively. Ca-Mg-HCO 3 followed by Na-Ca-HCO 3 -Cl are the primary water types in the study area. Pearson's correlation matrix showed a positive correlation between TDS and EC (r = 0.78) and sodium showed a positive correlation with TDS and bicarbonate (r = 0.62 and r = 0.65), respectively. Gibbs plot indicated that rock-water interaction is the dominant factor that controls the chemistry of the groundwater of the area. Irrigation parameters like Sodium Absorption Ratio (SAR), Permeability Index (PI), Magnesium Absorption Ratio (MAR), Kelly's Ratio (KR), and Irrigation Water Quality Index (IWQI) indicated that groundwater is overall suitable for irrigation. USSL diagram illustrated that most of the samples fell into the C2 (medium salinity) and S1 (low sodium hazard) categories. Wilcox plot showed the samples fell in excellent to good categories indicating fitness of groundwater for irrigation in the area., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study assessed the toxicity of the Sheathmar pesticide on Oreochromis mossambicus. The 96-h median lethal concentration (LC 50 ) was determined using probit analysis, with survivability assessed using general threshold survival models (GUTS). Over 45 days, fish exposed to sublethal Sheathmar doses were studied for changes in growth, blood profiles, and liver enzymes. According to the findings, the LC 50 values of Sheathmar for Oreochromis mossambicus at different time intervals were determined as follows: 3016.64 µg/l at 24 h, 2723.13 µg/l at 48 h, 2415.45 µg/l at 72 h, and 2154.87 µg/l at 96 h. The GUTS-SD model effectively predicted fish survivability after Sheathmar exposure. Sublethal exposure led to significant alterations in growth and hematological, biochemical, and stress enzyme parameters in Oreochromis mossambicus. Moreover, the correlation matrix, integrated biomarker response (IBR), and biomarker response index (BRI) highlighted significant impacts on multiple biomarkers in Oreochromis mossambicus. Thus, the results underscore the harmful effects of Sheathmar on Oreochromis mossambicus, indicating a need for further study and mitigation., Competing Interests: Declarations Consent to Participate Not Applicable. Consent for Publication All authors consented to publish. Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)