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One of the most intense geomagnetic storms of recent times occurred on 10–11 May 2024. With a peak negative excursion of Sym‐H below −500 nT, this storm is the second largest of the space era. Solar wind energy transferred through radiation and mass coupling affected the entire Geospace. Our study revealed that the dayside magnetopause was compressed below the geostationary orbit (6.6 RE) for continuously ∼6 hr due to strong Solar Wind Dynamic Pressure (SWDP). Tremendous compression pushed the bow‐shock also to below the geostationary orbit for a few minutes. Magnetohydrodynamic models suggest that the magnetopause location could be as low as 3.3RE. We show that a unique combination of high SWDP (≥15 nPa) with an intense eastward interplanetary electric field (IEFY ≥ 2.5 mV/m) within a super‐dense Interplanetary Coronal Mass Ejection lasted for 409 min–is the key factor that led to the strong ring current at much closer to the Earth causing such an intense storm. Severe electrodynamic disturbances led to a strong positive ionospheric storm with more than 100% increase in dayside ionospheric Total Electron Content (TEC), affecting GPS positioning/navigation. Further, an HF radio blackout was found to occur in the 2–12 MHz frequency band due to strong D‐ and E‐region ionization resulting from a solar flare prior to this storm. Plain Language Summary: Life and a habitable atmosphere are sustained on Earth thanks to the protective and far‐stretched magnetic shield around the Earth, known as the Magnetosphere, which protecting the humanosphere from the hazardous solar wind particles that are continuously emanated from the Sun. However, massive solar wind ejections from the Sun often disturb the Earth's magnetosphere and affect mankind and critical space‐ and ground‐based technological infrastructure. When higher amounts of the solar wind traveling with supersonic speeds impact, the Earth's magnetosphere compresses significantly, and the crucial satellites in space become directly exposed to hazardous solar wind. Further, strong and rapid disturbances in the geomagnetic field and ionosphere could significantly affect the operations of various technical systems on ground, like electrical power grids, GNSS‐based precise navigation, etc. The strongest geomagnetic storm of the past three decades has recently occurred on 10–11 May 2024. This study investigates the solar sources and the possible mechanisms responsible for the occurrence of such an intense geomagnetic storm and also details the drastic reconfiguration of Earth's magnetosphere and significant ionospheric disturbances observed during this storm. Key Points: Strong SWDP caused a highly compressed magnetosphere with magnetopause pushed below geostationary orbit (6.6 RE) continuously for 6 hrThe highly compressed magnetosphere led an intense ring current at much closer distance to the EarthA super‐dense ICME with high SWDP (>15 nPa) and IEFY (>2.5 mV/m) sustaining for 409 min ‐ a key factor responsible for this intense storm [ABSTRACT FROM AUTHOR]

Slope stability is essential for mitigating landslides and erosion risks, especially during heavy rainfall. Vegetation significantly enhances slope stability through soil reinforcement and erosion control. Plant roots stabilize the soil matrix, reducing the likelihood of shallow landslides. However, vegetation's impact varies, with different types potentially influencing slope stability differently—some may even worsen instability under specific conditions. Evidence shows that both rigid and flexible vegetation types improve erosion resistance and slope stability, making them a cost-effective stabilization strategy. Plant water uptake increases matric suction and results in drier slopes, further reinforcing the stability. The mechanical effects of roots, which enhance soil cohesion, combined with the hydrological benefits of improved water management, are crucial for maintaining slope integrity. The present research emphasizes the importance of integrating vegetation into slope management strategies to mitigate landslide risks effectively. Additional measures, including geotechnical advancements, policy development, and community involvement, will complement these efforts. Thus, a comprehensive understanding of vegetation's diverse impacts and root structures, alongside advanced numerical analysis methods, is crucial for optimizing vegetation-based slope stabilization and enhancing safety in landslide-prone areas. In this paper, the authors thoroughly examine and review the state-of-the-art slope stability analysis techniques. Different methods of slope stabilization concerning vegetation have been covered such as RAR, Root Morphology and Density Distribution, root tensile strength and biomechanics, Numerical Analysis, and Limit Equilibrium approaches are the categories under which these techniques are divided.

The surge in spinal cord injuries (SCI) attracted many neurobiologists to explore the underlying complex pathophysiology and to offer better therapeutic outcomes. The multimodal approaches to therapy in SCI have proven to be effective but to a limited extent. The clinical basics involve invasive procedures and limited therapeutic interventions, and most preclinical studies and formulations are yet to be translated due to numerous factors. In recent years, photobiomodulation therapy (PBMT) has found many applications in various medical fields. In most PBMT, studies on SCI have employed laser sources in experimental animal models as a non-invasive source. PBMT has been applied in numerous facets of SCI pathophysiology, especially attenuation of neuroinflammatory cascades, enhanced neuronal regeneration, reduced apoptosis and gliosis, and increased behavioral recovery within a short span. Although PBMT is specific in modulating mitochondrial bioenergetics, innumerous molecular pathways such as JAK-STAT, PI3K-AKT, NF-κB, MAPK, JNK/TLR/MYD88, ERK/CREB, TGF-β/SMAD, GSK3β-AKT-β-catenin, and AMPK/PGC-1α/TFAM signaling pathways have been or are yet to be exploited. PMBT has been effective not only in cell-specific actions in SCI such as astrocyte activation or microglial polarization or alterations in neuronal pathology but also modulated overall pathobiology in SCI animals such as rapid behavioral recovery. The goal of this review is to summarize research that has used PBMT for various models of SCI in different animals, including clarifying its mechanisms and prospective molecular pathways that may be utilized for better therapeutic outcomes., Competing Interests: Declarations. Ethical Approval: This declaration is not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

One of the most intense geomagnetic storms of recent times occurred on 10-11 May 2024. With a peak negative excursion of Sym-H below -500 nT, this storm is the second largest of the space era. Solar wind energy transferred through radiation and mass coupling affected the entire Geospace. Our study revealed that the dayside magnetopause was compressed below the geostationary orbit (6.6 RE) for continuously ∼6 hr due to strong Solar Wind Dynamic Pressure (SWDP). Tremendous compression pushed the bow-shock also to below the geostationary orbit for a few minutes. Magnetohydrodynamic models suggest that the magnetopause location could be as low as 3.3RE. We show that a unique combination of high SWDP (≥15 nPa) with an intense eastward interplanetary electric field (IEF Y  ≥ 2.5 mV/m) within a super-dense Interplanetary Coronal Mass Ejection lasted for 409 min-is the key factor that led to the strong ring current at much closer to the Earth causing such an intense storm. Severe electrodynamic disturbances led to a strong positive ionospheric storm with more than 100% increase in dayside ionospheric Total Electron Content (TEC), affecting GPS positioning/navigation. Further, an HF radio blackout was found to occur in the 2-12 MHz frequency band due to strong D- and E-region ionization resulting from a solar flare prior to this storm., (© 2024. The Author(s).)

Purpose: Soft tissue sarcomas (STS) due to their aggressive nature, pose challenges in achieving optimal local control (LC) rates following surgery. Brachytherapy offers precise delivery of high radiation doses to target tissues, potentially enhancing LC rates. This feasibility study explored the efficacy of perioperative high-dose-rate brachytherapy (PHDRB) and external beam radiation therapy (EBRT) in improving LC rates for STS, with a particular focus on interstitial brachytherapy and dose escalation strategies for high-risk patient sub-groups., Material and Methods: Seven patients with STS underwent conservative surgery and PHDRB between October 2020 and October 2023. PHDRB doses ranged from 3.0 to 3.5 Gy BID in 10 fractions, with or without subsequent EBRT, as indicated. EBRT was delivered in 4-5 weeks after surgical procedure at a dose of 45-50 Gy in 25 treatments, with daily dose of 1.8-2.0 Gy. Brachytherapy techniques and dosimetry guidelines were meticulously implemented to ensure optimal treatment delivery and minimize toxicity., Results: All seven patients tolerated treatment well without acute or late radiation-related complications. Excellent local disease control was achieved in all cases, but three patients developed distant metastases. The overall feasibility and efficacy of PHDRB in combination with EBRT were promising., Conclusions: This study underscores the feasibility and potential efficacy of PHDRB and EBRT for STS treatment. Despite limitations in sample size, the results are promising, warranting further investigation through multi-centric studies. The use of dose-escalated PHDRB in high-risk cases enabled more intensive treatment delivery directly to the tumor bed, which may be critical for enhancing local control in patients with aggressive or large tumors. In facilities with limited resources and a high patient burden, where conformal radiotherapy is unavailable, brachytherapy remains an excellent modality for boosting the tumor bed or serving as a radical radiotherapy treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Termedia.)

Acne Vulgaris or Acne is a multifactorial bacterial infection caused by Propionibacterium acne, leading to inflammation and decreased quality of life, especially in adolescence. Currently, antibiotics and retinoids are preferred for treating acne. However, their continuous usage may lead to anti-microbial resistance and other side effects. Therefore, research on developing effective strategies to reduce antimicrobial resistance and improve acne healing is ongoing. The current work reports the synthesis and evaluation of near-infrared light-absorbing copper sulfide (CuS) nanoparticles loaded with a biomolecule, Glycyrrhizin (Ga). The photothermal efficacy studies, and in-vitro and in-vivo experiments indicated that the Ga-CuS NPs generated localized hyperthermia in acne-causing bacteria, leading to their complete growth inhibition. The results indicated that the Ga-Cus NPs possess excellent antibacterial and anti-inflammatory properties in the acne and inflammatory models. This could be from the synergistic effect of CuS NPs mediated mild Photothermal effect and inherent pharmacological properties of Ga. Further detailed studies of the formulations can pave the way for application in cosmetic clinics for the effective and minimally invasive management of Acne-like conditions., (© 2024. Controlled Release Society.)

Prolonged use of very commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with undesired side effects, including gastrointestinal ulcers due to the non-selective inhibition of cyclooxygenases. We describe the development of an inflammatory-stimuli-responsive turn-on fluorogenic theranostic prodrug DCF-HS for adjuvant drug delivery. Upon activation by reactive oxygen species (ROS), the prodrug releases diclofenac DCF (active drug) and the NIR fluorophore DCI-NH2 along with carbonyl sulfide (COS). The second activation of COS by the enzyme carbonic anhydrase (CA) generates hydrogen sulfide (H 2 S). The prodrug was conveniently synthesized using multi-step organic synthesis. The UV-Vis and fluorescence studies revealed the selective reactivity of DCF-HS towards ROS such as H 2 O 2 in the aqueous phase and the desired uncaging of the drug DCF with turn-on NIR fluorescent reporter under physiological conditions. Furthermore, the release of fluorophore DCI-NH2 and drug DCF was confirmed using the reverse phase HPLC method. Compatibility of prodrug activation was studied next in the cellular medium. The prodrug DCF-HS was non-toxic in a representative cancer cell line (HeLa) and a macrophage cell line (RAW 264.7) up to 100 μM concentration, indicating its biocompatibility. The intracellular ROS-mediated activation of the prodrug with the release of NIR dye DCI-NH2 and H 2 S was investigated in HeLa cells using the H 2 S-selective probe WSP2. The anti-inflammatory activity of the active drug DCF from the prodrug DCF-HS was studied in the lipopolysaccharide (LPS)-induced macrophage cell line and compared to that of the parent drug DCF using western blot analysis and it was found that the active drug resulted in pronounced inhibition of COX-2 in a dose-dependent manner. Finally, the anti-inflammatory potential of the prodrug and the turn-on fluorescence were validated in the inflammation-induced Wister rat models.

Delayed wound healing is often caused by bacterial infections and persistent inflammation. Multifunctional materials with anti-bacterial, anti-inflammatory, and hemostatic properties are crucial for accelerated wound healing. In this study, we report a biomacromolecule-based scaffold (ArCh) by uniquely combining arabinogalactan (Ar) and chitosan (Ch) using a Schiff-based reaction. Further, the optimized ArCh scaffolds were loaded with Glycyrrhizin (GA: anti-inflammatory molecule) conjugated NIR light-absorbing Copper sulfide (CuS) nanoparticles. The resultant GACuS ArCh scaffolds were characterized for different wound healing parameters in in-vitro and in-vivo models. Our results indicated that GACuS ArCh scaffolds showed excellent swelling, biodegradation, and biocompatibility in vitro. Further results obtained indicated that GACuS ArCh scaffolds demonstrated mild hyperthermia and enhanced hemostatic, anti-oxidant, anti-bacterial, and wound-healing effects when exposed to NIR light. The scaffolds, upon further validation, may be beneficial in accelerating wound healing and tissue regeneration response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Celiac disease (CD) is an organ-specific autoimmune disorder that occurs in genetically predisposed individuals when exposed to exogenous dietary gluten. This exposure to wheat gluten and related proteins from rye and barley triggers an immune response which leads to the development of enteropathy associated with symptoms of bloating, diarrhea, or malabsorption. The sole current treatment is to follow a gluten-free diet for the rest of one's life. Intestinal barriers are enriched with Unconventional T cells such as iNKT, MAIT, and γδ T cells, which lack or express only a limited range of rearranged antigen receptors. Unconventional T cells play a crucial role in regulating mucosal barrier function and microbial colonization. Unconventional T cell populations are widely represented in diseased conditions, where changes in disease activity related to iNKT and MAIT cell reduction, as well as γδ T cell expansion, are demonstrated. In this review, we discuss the role and potential employment of Unconventional T cells as a therapeutic target in the pathophysiology of celiac disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Ulcerative colitis is characterized as a chronic immune-mediated inflammatory condition, affecting the intestinal gastroenteric tissue. Previous studies revealed that Th-17 cells are key players in the pathogenesis of ulcerative colitis. RORγT (Retinoic-acid-receptor-related orphan receptor-gamma T) is a lineage-specific transcription factor of Th-17 cells and thus has a role in their differentiation. Transient inhibition of RORγT has been reported to attenuate the differentiation of Th-17 cells and secretion of interleukin-17 (IL-17). Here, we investigated the efficacy of topotecan in ameliorating ulcerative colitis in rodents, via inhibition of the RORγT transcription factor., Main Methods and Key Findings: Experimental ulcerative colitis was induced in rats by intrarectal acetic acid administration. Topotecan attenuated the severity of ulcerative colitis in rats by revoking neutrophils and macrophage infiltration to the colon. It also alleviated diarrhea and rectal bleeding and improved body weight. Further, attenuation of RORγT and IL-17 expression was observed in topotecan treated animals. Levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the colon tissue were reduced by topotecan treatment. Significant reduction in malondialdehyde level, elevation of superoxide dismutase (SOD) and catalase activity was observed in the colon tissue of rats treated with topotecan compared to the diseased group., Significance: This study shows the therapeutic potential of topotecan in attenuating ulcerative colitis in rats probably via inhibition of the RORγT transcription factor and downstream mediators of Th-17 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China in December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious and still-unfolding health conditions and economic ramifications. Based on the clinical investigations, the severity of COVID-19 appears to be highly variable, ranging from mild to severe infections including the death of an infected individual. To add to this, patients with comorbid conditions such as age or concomitant illnesses are significant predictors of the disease's severity and progression. SARS-CoV-2 enters inside the host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated with higher ACE2 expression may enhance the virus entry and the severity of COVID-19 infection. It has already been recognized that age-related comorbidities such as Parkinson's disease, cancer, diabetes, and cardiovascular diseases may lead to life-threatening illnesses in COVID-19-infected patients. COVID-19 infection results in the excessive release of cytokines, called "cytokine storm", which causes the worsening of comorbid disease conditions. Different mechanisms of COVID-19 infections leading to intensive care unit (ICU) admissions or deaths have been hypothesized. This review provides insights into the relationship between various comorbidities and COVID-19 infection. We further discuss the potential pathophysiological correlation between COVID-19 disease and comorbidities with the medical interventions for comorbid patients. Toward the end, different therapeutic options have been discussed for COVID-19-infected comorbid patients., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

A new lithocholic acid/IR 780 conjugate (LIC) was designed and synthesized for theranostic applications in triple-negative breast cancer. Lithocholic acid is an antitumor biomacromolecule and acts via multiple molecular targets. IR 780 iodide is a fluorescent NIR organic dye researched as a photothermal agent in cancer therapy. A combined conjugate, LIC can have wide applications as a Photothermal/chemotherapeutic and imaging agent in cancer therapy. LIC was characterized and evaluated for its photothermal cytotoxic effect in breast cancer cell lines. Further, to improve the bioavailability of the LIC, a polymeric (PLGA) nanosystem was developed and characterized. The resultant lithocholic acid/IR 780 polymeric nanoconjugates (LIPNCs) were well taken up by the cells and are evident by the inherent red fluorescence of LIC. The LIPNCs also exhibited commendable heat generation when exposed to NIR light (808 nm). The in-vitro anti-cancer studies of LIPNCs also revealed a significant NIR light-based photothermal efficacy (cytotoxic dose 0.75 μM) when compared to the free conjugate (LIC) or the parent moieties. Further cell-based fluorescent and molecular assays showed that LIPNCs induced ROS-mediated apoptotic cell death concurrently being physiologically biocompatible. In-vitro photoacoustic imaging of the LICs exhibited signals comparable to free IR780 dye. Future in vivo studies with LIPNCs or LIC may prove beneficial for developing a promising translational system for its wide application in image-guided cancer theranostics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of interest There are no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The novel enveloped β-coronavirus SARS-CoV-2 (COVID-19) has offered a surprising health challenge all over the world. It develops severe pneumonia leading to acute respiratory distress syndrome (ARDS). Like SARS-COV-2, other encapsulated viruses like HIV, HSV, and influenza have also offered a similar challenge in the past. In this regard, many antiviral drugs are being explored with varying degrees of success to combat the associated pathological conditions. Therefore, upon scientific validation & development, these antiviral phytochemicals can attain a futuristic nutraceutical prospect in managing different encapsulated viruses. Houttuynia cordata (HC) is widely reported for activities such as antioxidant, anti-inflammatory, and antiviral properties. The major antiviral bioactive components of HC include essential oils (methyl n-nonyl ketone, lauryl aldehyde, capryl aldehyde), flavonoids (quercetin, rutin, hyperin, quercitrin, isoquercitrin), and alkaloids (norcepharadione B) & polysaccharides. HC can further be explored as a potential nutraceutical agent in the therapy of encapsulated viruses like HIV, HSV, and influenza. The review listed various conventional and green technologies that are being employed to extract potent phytochemicals with diverse activities from the HC. It was indicated that HC also inhibited molecular targets like 3C-like protease (3CLPRO) and RNA-dependent RNA polymerase (RdRp) of COVID-19 by blocking viral RNA synthesis and replication. Antioxidant and hepatoprotective effects of HC have been evident in impeding complications from marketed drugs during antiviral therapies. The use of HC as a nutraceutical is localized within some parts of Southeast Asia. Further technological advances can establish it as a nutraceutical-based functional food against pathogenic enveloped viruses like COVID 19., Competing Interests: The authors declare no conflicts of interest., (© 2022 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a chronic motor disorder, characterized by progressive loss of dopaminergic neurons. Numerous studies suggest that glucagon-like peptide-1 (GLP-1) secretagogue has a neuroprotective role in PD models. The present study evaluated potential of coffee bioactive compounds in terms of their ability to bind GPR-40/43 and tested the neuroprotective effect of best candidate on rotenone-induced PD mice acting via GLP-1 release. In silico molecular docking followed by binding free energy calculation revealed that chlorogenic acid (CGA) has a strong binding affinity for GPR-40/43 in comparison to other bioactive polyphenols. Molecular dynamics simulation studies revealed stable nature of GPR40-CGA and GPR43-CGA interaction and also provided information about the amino acid residues involved in binding. Subsequently, in vitro studies demonstrated that CGA-induced secretion of GLP-1 via enhancing cAMP levels in GLUTag cells. Furthermore, in vivo experiments utilizing rotenone-induced mouse model of PD revealed a significant rise in plasma GLP-1 after CGA administration (50 mg/kg, orally for 13 weeks) with concomitant increase in colonic GPR-40 and GPR-43 mRNA expression. CGA treatment also prevented rotenone-induced motor and cognitive impairments and significantly restored the rotenone-induced oxidative stress. Meanwhile, western blot results confirmed that CGA treatment downregulated rotenone-induced phosphorylated alpha-synuclein levels by upregulating PI3K/AKT signaling and inactivating GSK-3β through the release of GLP-1. CGA treatment ameliorated rotenone-induced dopaminergic nerve degeneration and alpha-synuclein accumulation in substantia nigra and augmented mean density of dopaminergic nerve fibers in striatum. These findings demonstrated novel biological function of CGA as a GLP-1 secretagogue. An increase in endogenous GLP-1 may render neuroprotection against a rotenone mouse model of PD and has the potential to be used as a neuroprotective agent in management of PD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease (PD) patients not only show motor features such as bradykinesia, tremor, and rigidity but also non-motor features such as anxiety, depression, psychosis, memory loss, attention deficits, fatigue, sexual dysfunction, gastrointestinal issues, and pain. Many pharmacological treatments are available for PD patients; however, these treatments are partially or transiently effective since they only decrease the symptoms. As these therapies are unable to restore dopaminergic neurons and stop the development of Parkinson's disease, therefore, the need for an effective therapeutic approach is required. The current review summarizes novel targets for PD, that can be utilized to identify disease-modifying treatments., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With the scaling of lateral dimensions in advanced transistors, an increased gate capacitance is desirable both to retain the control of the gate electrode over the channel and to reduce the operating voltage 1 . This led to a fundamental change in the gate stack in 2008, the incorporation of high-dielectric-constant HfO 2  (ref.  2 ), which remains the material of choice to date. Here we report HfO 2 -ZrO 2 superlattice heterostructures as a gate stack, stabilized with mixed ferroelectric-antiferroelectric order, directly integrated onto Si transistors, and scaled down to approximately 20 ångströms, the same gate oxide thickness required for high-performance transistors. The overall equivalent oxide thickness in metal-oxide-semiconductor capacitors is equivalent to an effective SiO 2 thickness of approximately 6.5 ångströms. Such a low effective oxide thickness and the resulting large capacitance cannot be achieved in conventional HfO 2 -based high-dielectric-constant gate stacks without scavenging the interfacial SiO 2 , which has adverse effects on the electron transport and gate leakage current 3 . Accordingly, our gate stacks, which do not require such scavenging, provide substantially lower leakage current and no mobility degradation. This work demonstrates that ultrathin ferroic HfO 2 -ZrO 2 multilayers, stabilized with competing ferroelectric-antiferroelectric order in the two-nanometre-thickness regime, provide a path towards advanced gate oxide stacks in electronic devices beyond conventional HfO 2 -based high-dielectric-constant materials., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)