Pain is a complex and multifaceted experience. Recent research has increasingly focused on the role of endoplasmic reticulum (ER) stress in the induction and modulation of pain. The ER is an essential organelle for cells and plays a key role in protein folding and calcium dynamics. Various pathological conditions, such as ischemia, hypoxia, toxic substances, and increased protein production, may disturb protein folding, causing an increase in misfolding proteins in the ER. Such an overload of the folding process leads to ER stress and causes the unfolded protein response (UPR), which increases folding capacity in the ER. Uncompensated ER stress impairs intracellular signaling and cell function, resulting in various diseases, such as diabetes and degenerative neurological diseases. ER stress may be a critical universal mechanism underlying human diseases. Pain sensations involve the central as well as peripheral nervous systems. Several preclinical studies indicate that ER stress in the nervous system is enhanced in various painful states, especially in neuropathic pain conditions. The purpose of this narrative review is to uncover the intricate relationship between ER stress and pain, exploring molecular pathways, implications for various pain conditions, and potential therapeutic strategies. Full article

The traditional design method for terahertz metasurface biosensors is cumbersome and time-consuming, requires expertise, and often leads to significant discrepancies between expected and actual values. This paper presents a novel approach for the fast, efficient, and convenient inverse design of THz metasurface sensors, leveraging convolutional neural network techniques based on deep learning. During the model training process, the magnitude data of the scattering parameters collected from the numerical simulation of the THz metasurface served as features, paired with corresponding surface structure matrices as labels to form the training dataset. During the validation process, the thoroughly trained model precisely predicted the expected surface structure matrix of a THz metasurface. The results demonstrate that the proposed algorithm realizes time-saving, high-efficiency, and high-precision inversion methods without complicated data preprocessing and additional optimization algorithms. Therefore, deep learning algorithms offer a novel approach for swiftly designing and optimizing THz metasurface sensors in biomedical detection, bypassing the complex and specialized design process of electromagnetic devices, and promising extensive prospects for their application in the biomedical field. Full article

Recent increases in gas-fired power generation have engendered increased interdependencies between natural gas and power transmission systems. These interdependencies have amplified existing vulnerabilities in gas and power grids, where disruptions can require the curtailment of load in one or both systems. Although typically operated independently, coordination of these systems during severe disruptions can allow for targeted delivery to lifeline services, including gas delivery for residential heating and power delivery for critical facilities. To address the challenge of estimating maximum joint network capacities under such disruptions, we consider the task of determining feasible steady-state operating points for severely damaged systems while ensuring the maximal delivery of gas and power loads simultaneously, represented mathematically as the nonconvex joint Maximal Load Delivery (MLD) problem. To increase its tractability, we present a mixed-integer convex relaxation of the MLD problem. Then, to demonstrate the relaxation’s effectiveness in determining bounds on network capacities, exact and relaxed MLD formulations are compared across various multi-contingency scenarios on nine joint networks ranging in size from 25 to 1191 nodes. The relaxation-based methodology is observed to accurately and efficiently estimate the impacts of severe joint network disruptions, often converging to the relaxed MLD problem’s globally optimal solution within ten seconds. Full article

Alberta’s forest industry is predicted to be impacted by a medium-term decline in timber supply. Intensive silviculture tools, such as pre-commercial thinning, have been shown to increase individual tree growth, shorten rotation lengths, and improve stand merchantability in important commercial species such as lodgepole pine. However, lodgepole pine stands are susceptible to western gall rust infections, and thinning at an early stage may increase infection rates. This study collected tree and stand level data from 33 operational harvest origin lodgepole pine stands consisting of 11 stands thinned at age 17–19 years (PCT_18), 11 stands thinned at age 23–25 (PCT_24), and 11 unthinned stands. Approximately 40 years after pre-commercial thinning, merchantable volume is similar in all stands but thinned stands, regardless of timing, had greater individual tree size (~15% higher) compared to unthinned stands. Pre-commercially thinned stands also had a higher potential for commercial thinning since they have lower variability in tree size and longer live crown lengths. In addition, delayed thinning (PCT_24) reduced western gall rust infections and the severity of infections compared to both PCT_18 and unthinned stands. In conclusion, pre-commercial thinning should be considered for lodgepole pine stands in order to address timber supply issues in Alberta. Full article

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl₂, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl₂ treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl₂ was inhibited by MMP7 knockdown, suggesting that MgCl₂ enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl₂ inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial. Full article

The global issue for proton exchange membrane fuel cell market development is a reduction in the device cost through an increase in efficiency of the oxygen reduction reaction occurring at the cathode and an extension of the service life of the electrochemical device. Losses in the fuel cell performance are due to various degradation mechanisms in the catalytic layers taking place under conditions of high electric potential, temperature, and humidity. This review is devoted to recent advances in the field of increasing the efficiency and durability of electrocatalysts and other electrode materials by introducing structured carbon components into their composition. The main synthesis methods, physicochemical and electrochemical properties of materials, and performance of devices on their basis are presented. The main correlations between the composition and properties of structured carbon electrode materials, which can provide successful solutions to the highlighted issues, are revealed. Full article

Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1^fl/fl) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD. Full article

Water scarcity is an important threat to food security in the Tigris–Euphrates river system. Water scarcity is a huge worldwide problem that results from the rapid increase in water demand, which exceeds the amount of available water. The most significant problems currently affecting countries are food insecurity water scarcity. The Tigris–Euphrates river system countries suffer from different political issues, such as the Syrian war and internal civil conflicts in Iraq. In addition, this area consists of only three countries: Iraq, Syria, and Turkey, but it affects the entire Middle East. Turkey has established many irrigation projects compared to Iraq, which still suffers from the previous American invasion. Therefore, this study examines the Tigris–Euphrates river system (using two countries) to examine the relationship between water scarcity and food security from 1992 to 2020. This study will be conducted using a fixed and random regression approach over 18 years. The results show a negative relationship between water scarcity and food security in the short run, at a 10% significance level, and a long-term positive relationship of 1%. Thus, the use of research and development and the encouragement of investments will help policymakers to develop a nexus between water scarcity and food security. Full article

This paper aims to emphasize the need for enhancing inclusivity and accessibility within smart-city societies. It represents the first attempt to apply Amartya Sen’s capability approach by exploring the implications of digital divides for promoting inclusive and climate-friendly cities that prioritize well-being, equity, and societal participation. Sen’s framework recognizes individual variations in converting resources into valuable ‘functionings’, and herein emphasizes the importance of aligning personal, social, and environmental conversion factors for individuals to fully navigate, participate in, and enjoy the benefits provided by smart cities. Adopting the capability approach and employing a cross-disciplinary analysis of the scientific literature, the primary objective is to broaden understanding of how to improve inclusivity and accessibility within smart-city societies, with a specific focus on marginalized community members facing first- and second-level digital divides. This paper underscores the importance of adopting a systemic perspective on climate-smart city navigation and stresses the importance of establishing a unified governing body responsible for monitoring, evaluating, and enhancing smart-city functionality. The paper concludes by summarizing some policy recommendations to boost social inclusion and address climate change in smart cities, such as creating capability-enhancing institutions, safeguarding redundancy in public-choice options, empowering citizens, and leveraging academic knowledge in smart-city policy formulation. Full article

In Germany, there are over 32,000 schools, representing great potential for climate protection. On the one hand, this applies to educational work, as understanding the effects of climate change and measures to reduce GHG emissions is an important step to empower students with knowledge and skills. On the other hand, school buildings are often in bad condition, energy is wasted, and the possibilities for using renewable energies are hardly used. In our “Schools4Future” project, we enabled students and teachers to draw up their own CO₂ balances, identify weaknesses in the building, detect wasted electricity, and determine the potential for using renewable energies. Emissions from the school cafeteria, school trips, and paper consumption could also be identified. The fact that the data can be collected by the students themselves provides increased awareness of the contribution made to the climate balance by the various school areas. The most climate-friendly school emits 297 kg whilst the school with the highest emissions emits over one ton CO₂ per student and year. Our approach is suitable to qualify students in the sense of citizen science, carry out a scientific investigation, experience self-efficacy through one’s own actions, and engage politically regarding their concerns. Full article

Wounds are breaks in the continuity of the skin and underlying tissues, resulting from external causes such as cuts, blows, impacts, or surgical interventions. Countless individuals suffer minor to severe injuries, with unfortunate cases even leading to death. In today’s scenario, several commercial products are available to facilitate the healing process of wounds, although chronic wounds still present more challenges than acute wounds. Nevertheless, the huge demand for wound-care products within the healthcare sector has given rise to a rapidly growing market, fostering continuous research and development endeavors for innovative wound-healing solutions. Today, there are many commercially available products including those based on natural biopolymers, stem cells, and microRNAs that promote healing from wounds. This article explores the recent breakthroughs in wound-healing products that harness the potential of natural biopolymers, stem cells, and microRNAs. A comprehensive exploration is undertaken, covering not only commercially available products but also those still in the research phase. Additionally, we provide a thorough examination of the opportunities, obstacles, and regulatory considerations influencing the potential commercialization of wound-healing products across the diverse markets of Europe, America, and Asia. Full article

To explore how endophytic microbial compositions in amaranth roots are influenced by various fertilization methods and to determine whether these microbes are associated with amaranthin formation, we conducted an analysis of the endophytic microbial community structure. The roots of amaranth plants subjected to different fertilization treatments—conventional fertilization without potassium (NP), conventional fertilization without phosphorus (NK), conventional fertilization without nitrogen (PK), and balanced fertilization (NPK)—were examined. The results showed that the proportions of Streptomyces, Actinospica, and Burkholderia-Caballeronia-Paraburkholderia in the amaranth roots under the balanced fertilization (NPK) treatment were all greater than those in the amaranth roots under the nitrogen (PK), phosphorus (NK), and potassium (NP) deficiency fertilization treatments. In contrast, the proportions of Phenylobacterium, Acrocalymma, Neocosmospora, Fusarium, Acidovorax, Gibellulopsis, Cladosporium, Dactylonectria, and Gibberella in the amaranth roots under the nutrient deficiency fertilization (NP, NK, and PK) treatments were higher than those in the amaranth roots under the balanced fertilization treatment. Additionally, a significantly positive correlation was found between Streptomyces and the amaranthin content. Furthermore, Acrocalymma, Neocosmospora, and Fusarium exhibited significantly negative correlations with the amaranthin content. The above results suggested that endophytes could easily colonize in amaranth roots as beneficial microorganisms under balanced fertilization conditions. In other words, the balanced fertilization (N, P and K fertilizers are 188.0, 53.0 and 50.0 kg·hm⁻², respectively) could recruit more beneficial endogenous microorganisms in amaranth roots for improving their growth and quality. Full article

In 2022, an unprecedented outbreak of mpox raged in several nations. Sequences from the 2022 outbreak reveal a higher nucleotide substitution if compared with the estimated rate for orthopoxviruses. Recently, intra-lesion SNVs (single nucleotide variants) have been described, and these have been suggested as possible sources of genetic variation. Until now, it has not been clear if the presence of several SNVs could represents the result of local mutagenesis or a possible co-infection. We investigated the significance of SNVs through whole-genome sequencing analysis of four unrelated mpox cases. In addition to the known mutations harboured by the circulating strains of virus (MPXV), 7 novel mutations were identified, including SNVs located in genes that are involved in immune evasion mechanisms and/or viral fitness, six of these appeared to be APOBEC3-driven. Interestingly, three patients exhibited the coexistence of mutated and wild-type alleles for five non-synonymous variants. In addition, two patients, apparently unrelated, showed an analogous pattern for two novel mutations, albeit with divergent frequencies. The coexistence of mixed viral populations, harbouring non-synonymous mutations in patients, supports the hypothesis of possible co-infection. Additional investigations of larger clinical cohorts are essential to validating intra-patient viral genome heterogeneity and determining the possibility of co-presence events of slightly divergent MPXV strains. Full article

mTOR is a central regulator of cell growth and metabolism in response to mitogenic and nutrient signals. Notably, mTOR is not only found in the cytoplasm but also in the nucleus. This review highlights direct involvement of nuclear mTOR in regulating transcription factors, orchestrating epigenetic modifications, and facilitating chromatin remodeling. These effects intricately modulate gene expression programs associated with growth and metabolic processes. Furthermore, the review underscores the importance of nuclear mTOR in mediating the interplay between metabolism and epigenetic modifications. By integrating its functions in nutrient signaling and gene expression related to growth and metabolism, nuclear mTOR emerges as a central hub governing cellular homeostasis, malignant transformation, and cancer progression. Better understanding of nuclear mTOR signaling has the potential to lead to novel therapies against cancer and other growth-related diseases. Full article

The Chinese Loess Plateau has undergone extensive revegetation to restore degraded land and enhance carbon sequestration. However, soil organic carbon (SOC) sequestrated in the soil profiles of deep-rooted plants has not been fully studied. Here, we investigated the SOC within a 0–23 m profile in farmlands and apple orchards converted from farmlands with different ages (A5, <5 years; A10, ~10 years; A15, ~15 years; A20, >20 years) and the controlling factors on three loess tablelands (Changwu, Qingyang, and Luochuan). The results show that SOC stocks among farmlands and orchards showed no significant difference (p = 0.88); however, SOC stocks showed a trend with tree ages, i.e., a decrease for A5 and A10 but an increase for A15 and A20. For the vertical variability, the SOC stock was the highest within 0–1 m, regardless of the standing age; however, the SOC stock in this layer only accounted for 8.8% of the total SOC stock (97.93 ± 9.18 kg m⁻²). Climate accounted for 82% of the variations and controlled the changes in SOC in the 0–1 m range, while soil texture dominated the SOC in the soil below 1 m, accounting for 57% of the SOC variations. The variations in SOC in the thick, unsaturated zones provide implications for future land use management and the sustainability of apple orchards in arid regions. Full article

In this study, the fatigue strength of polished drill pipe specimens was investigated and compared with previous test results of corroded and not-corroded pipes. The resonant fatigue test rig, which was designed and implemented by the University of Pisa, is initially presented by providing a detailed description of the set-up of the machine, the calibration of the strain gauges, the control system, and the correct identification of the vibrational node locations. A polishing rig was also designed and put into operation to remove the corrosion pits from the outer surface of almost the entire length of the drill pipe specimens. After the fatigue tests with the resonant rig, and the observation of the fatigue fracture of the specimens, a few samples were extracted from different zones (corroded and not corroded) of the failed drill pipe specimens. This allowed for investigations to be carried out using a scanning electronic microscope. The obtained results were analyzed using the Murakami model, and a discussion is presented about the effect of the corrosion pits on the fatigue strength. Full article

Many liqueurs, including spirits infused with botanicals, are crafted not only for their taste and flavor but also for potential medicinal benefits. However, the scientific evidence supporting their medicinal effects remains limited. This study aims to verify in vitro anticancer activity and bioactive compounds in shochu spirits infused with Cordyceps militaris, a Chinese medicine. The results revealed that a bioactive fraction was eluted from the spirit extract with 40% ethanol. The infusion time impacted the inhibitory effect of the spirit extract on the proliferation of colon cancer-derived cell line HCT-116 cells, and a 21-day infusion showed the strongest inhibitory effect. Furthermore, the spirit extract was separated into four fractions, A-D, by high-performance liquid chromatography (HPLC), and Fractions B, C, and D, but not A, exerted the effects of proliferation inhibition and apoptotic induction of HCT-116 cells and HL-60 cells. Furthermore, Fractions B, C, and D were, respectively, identified as adenosine, cordycepin, and N⁶-(2-hydroxyethyl)-adenosine (HEA) by comprehensive chemical analyses, including proton nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FT-IR), and electrospray ionization mass spectrometry (ESI-MS). To better understand the bioactivity mechanisms of cordycepin and HEA, the agonist and antagonist tests of the A3 adenosine receptor (A3AR) were performed. Cell viability was suppressed by cordycepin, and HEA was restored by the A3AR antagonist MR1523, suggesting that cordycepin and HEA possibly acted as agonists to activate A3ARs to inhibit cell proliferation. Molecular docking simulations revealed that both adenosine and cordycepin bound to the same pocket site of A3ARs, while HEA exhibited a different binding pattern, supporting a possible explanation for the difference in their bioactivity. Taken together, the present study demonstrated that cordycepin and HEA were major bioactive ingredients in Cordyceps militaries-infused sweet potato shochu spirits, which contributed to the in vitro anticancer activity. Full article

African horse sickness is a severe and often fatal disease affecting all species of equids. The aetiological agent, African horse sickness virus (AHSV), can be differentiated into nine serotypes. The identification of AHSV serotypes is vital for disease management, as this can influence vaccine selection and help trace disease incursion routes. In this study, we report the development and optimisation of a novel, molecular-based assay that utilises multiplex PCR and microsphere-based technology to expedite detection and differentiation of multiple AHSV serotypes in one assay. We demonstrated the ability of this assay to identify all nine AHSV serotypes, with detection limits ranging from 1 to 277 genome copies/µL depending on the AHSV serotype. An evaluation of diagnostic sensitivity and specificity revealed a sensitivity of 88% and specificity of 100%. This method can serotype up to 42 samples per run and can be completed in approximately 4–6 h. It provides a powerful tool to enhance the rapidity and efficiency of AHSV serotype detection, thereby facilitating the generation of epidemiological data that can help understand and control the incidence of AHSV worldwide. Full article

Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50–64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62–0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52–1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence. Full article

Ultrasonic vibration-assisted con-rod fracture splitting (UV-CFS) was used to carry out the fracture experiment of 1045 quenched and tempered steel. The effect of ultrasonic vibration on the fracture properties was studied, the fracture microstructure and the evolution of dislocations near the fracture were analyzed and the microscopic mechanism was analyzed. The results show that in the case of conventional fracture splitting without amplitude, the dimple and the fracture belong to ductile fracture. With the increase in ultrasonic amplitude, the plasticity and pore deformation of the con-rod samples decrease at first and then increase; when the amplitude reaches a certain point, the load required for cracking is reduced to a minimum and the ultrasonic hardening effect is dominant, resulting in a decrease in the plasticity of the sample, a cleavage fracture, a brittle fracture, the minimum pore deformation and high cracking quality. The research results also show that with the increase in ultrasonic amplitude, the fracture dislocation density decreases at first, then increases, and dislocation entanglement and grain breakage appear, then decrease, and multiple dislocation slip trajectories appear. The changes in the dislocation density and microstructure are consistent with the above results. Full article

An accurate simulation and projection of future warming are needed for a proper policy response to expected climate change. We examine the simulations of the mean global and Arctic surface air temperatures by the CMIP6 (Climate Models Intercomparison Project phase 6) climate models. Most models overestimate the observed mean global warming. Only seven out of 19 models considered simulate global warming that is within ±15% of the observed warming between the average of the 2014–2023 and 1961–1990 reference period. Ten models overestimate global warming by more than 15% and only one of the models underestimates it by more than 15%. Arctic warming is simulated by the CMIP6 climate models much better than the mean global warming. The reason is an equal spread of over and underestimates of Arctic warming by the models, while most of the models overestimate the mean global warming. Eight models are within ±15% of the observed Arctic warming. Only three models are accurate within ±15% for both mean global and Arctic temperature simulations. Full article

RAMOSA1 (RA1) is a Cys2-His2-type (C2H2) zinc finger transcription factor that controls plant meristem fate and identity and has played an important role in maize domestication. Despite its importance, the origin of RA1 is unknown, and the evolution in plants is only partially understood. In this paper, we present a well-resolved phylogeny based on 73 amino acid sequences from 48 embryophyte species. The recovered tree topology indicates that, during grass evolution, RA1 arose from two consecutive SUPERMAN duplications, resulting in three distinct grass sequence lineages: RA1-like A, RA1-like B, and RA1; however, most of these copies have unknown functions. Our findings indicate that RA1 and RA1-like play roles in the nucleus despite lacking a traditional nuclear localization signal. Here, we report that copies diversified their coding region and, with it, their protein structure, suggesting different patterns of DNA binding and protein–protein interaction. In addition, each of the retained copies diversified regulatory elements along their promoter regions, indicating differences in their upstream regulation. Taken together, the evidence indicates that the RA1 and RA1-like gene families in grasses underwent subfunctionalization and neofunctionalization enabled by gene duplication. Full article