Critical Factor Research Articles

Herbs Used for the Management of Hypertension: A Systematic Review

Background: Hypertension is characterized by persistent high blood pressure and has emerged as a critical risk factor for severe cardiovascular diseases. Although several drugs have been designated to reduce blood pressure, these drugs can potentially cause side effects for patients. Therefore, medicinal plants are used to complement conventional drugs to treat various ailments. Methods: This study reviews the anti-hypertensive potential of herbs and plants and their mechanism of action in reducing blood pressure at their evaluated effective doses. Databases such as PubMed, Scopus, Science Direct, and Google Scholar were used to search articles from January 2016 to Sept 2022. The key search terms included “hypertension”, “lowers blood pressure”, “anti-hypertensive”, and “plants”. These generated 807 documents and using the PRISMA guidelines, thirty plants were identified for this review. Research studies with similar plant parts extracted from similar solvents, more than one dose, and animal models with a positive control were considered in this review. Studies that did not show significant blood pressure reduction were excluded. Results: Based on this criterion, the mechanism of actions of these plants was thematically grouped into three categories, namely 1) antioxidant, 2) angiotensin-converting enzyme (ACE) inhibition, and 3) calcium influx in vascular smooth muscle. The effective doses, plant parts used, and traditional medicine usage are presented in this review. Conclusion: Further research is highly recommended to identify the active compounds and to potentially develop them into anti-hypertensive drugs as well as to establish the safe doses and standardization of these plant extracts. This review is partially funded by grants from the Ministry of Higher Education.

Immunoengineering Biomaterials for Musculoskeletal Tissue Repair across Lifespan.

Musculoskeletal diseases and injuries are among the leading causes of pain and morbidity worldwide. Broad efforts have focused on developing pro-regenerative biomaterials to treat musculoskeletal conditions; however, these approaches have yet to make a significant clinical impact. Recent studies have demonstrated that the immune system is central in orchestrating tissue repair and that targeting pro-regenerative immune responses can improve biomaterial therapeutic outcomes. However, aging is a critical factor negatively affecting musculoskeletal tissue repair and immune function. Hence, understanding how age affects the response to biomaterials is essential for improving musculoskeletal biomaterial therapies. This review focuses on the intersection of the immune system and aging in response to biomaterials for musculoskeletal tissue repair. The article introduces the general impacts of aging on tissue physiology, the immune system, and the response to biomaterials. Then, it explains how the adaptive immune system guides the response to injury and biomaterial implants in cartilage, muscle, and bone and discusses how aging impacts these processes in each tissue type. The review concludes by highlighting future directions for the development and translation of personalized immunomodulatory biomaterials for musculoskeletal tissue repair.

The Effect of Innovation on the Performance of SMEs in Zimbabwe: A Case Study of Manufacturing Companies in Harare

Technological Innovation has become an indispensable tool for organizations to gain competitive advantage, increase performance, venture into new markets and survive in such a competitive atmosphere. A plethora of research has found that technological innovation is a critical factor that improves organizational performance. The study focused on investigating the effects of technological innovation on the performance of SMEs in the manufacturing industry. The study objectives were to establish the factors that influence technological innovativeness among manufacturing SMEs in Zimbabwe, determine the effect of product innovation on the performance of manufacturing SMEs, to ascertain the effect of process innovation on the performance of manufacturing SMEs in Zimbabwe and to establish the challenges faced by SMEs in the manufacturing sector adopting technological innovation in Zimbabwe. A quantitative research approach was adopted. The researcher used simple random sampling in this study and every member in the sample size has an equal opportunity to be selected. A total sample size of 66 respondents was selected randomly. A structured questionnaire was distributed to respondents and the response rate was approximately 76%. Data was processed on excel which was later uploaded on the SPSS and SmartPLS version 3.2.1 softwares. Cronbach Alpha of 0.886 was obtained and this indicated the strong reliability and validity of the study results. Composite and Average variance extracted was also used to assessed the validity of the study. It was discovered that experienced human capital, leadership, access to funding, competition, and organisation mission and culture are important in influencing innovation in SMEs. In addition, the study revealed that product and process innovation had an impact on manufacturing SMEs’ organizational performance that was statistically significant. It emerged that product and process innovation improves a number of financial performance indicators for a business, including sales growth, market expansion, rising customer happiness, and rising profit margins. Therefore, in line with the findings, the study recommends that the government must develop and implement a wide range of innovation policies that encourage best practices and support company growth and should support the creation and ongoing operation of innovative businesses through partnerships. Future studies should expand the study’s scope and sample size and other factors related to product and process innovations. In addition, future research has to take into account the creation of national and regional government policies that encourage innovation among SMEs.

Strategic human resource management for sustainability in creative industries: A review and framework proposal

Strategic Human Resource Management (SHRM) has emerged as a critical approach for fostering sustainability within the dynamic landscape of creative industries. This review presents a comprehensive review of existing literature on SHRM in the context of creative industries, culminating in a proposed framework aimed at enhancing sustainability in these sectors. The review begins by examining the unique challenges faced by creative industries, characterized by rapid technological advancements, evolving consumer preferences, and intense competition. In this context, traditional HRM approaches are often insufficient, necessitating a strategic alignment between HR practices and organizational objectives to ensure long-term viability. Key themes identified in the literature review include talent management, organizational culture, employee engagement, and leadership development. Effective talent management strategies are crucial for attracting, retaining, and developing skilled individuals who drive innovation and creativity within creative firms. Furthermore, fostering a supportive organizational culture that values diversity, collaboration, and experimentation is vital for promoting sustainability in these industries. Employee engagement emerges as a critical factor influencing organizational performance and resilience, particularly in creative environments where intrinsic motivation plays a significant role. Moreover, leadership development programs tailored to the unique needs of creative professionals can empower individuals to navigate uncertainty and drive strategic initiatives that contribute to organizational sustainability. Building upon these insights, this review proposes a framework for SHRM in creative industries, integrating strategic planning, talent management, culture development, and leadership practices. The framework emphasizes the alignment between HR strategies and business goals, emphasizing the importance of agility, innovation, and adaptability in response to dynamic market conditions. Strategic Human Resource Management plays a pivotal role in enhancing sustainability within creative industries by fostering a culture of innovation, empowering employees, and cultivating leadership capabilities. The proposed framework provides a roadmap for organizations seeking to navigate the complexities of the creative landscape while maximizing long-term success and resilience.

Decreasing exciton dissociation rates for reduced voltage losses in organic solar cells

Enhancing the device electroluminescence quantum efficiency (EQEEL) is a critical factor in mitigating non-radiative voltage losses (VNR) and further improving the performance of organic solar cells (OSCs). While the common understanding attributes EQEEL in OSCs to the dynamics of charge transfer (CT) states, persistent efforts to manipulate these decay dynamics have yielded limited results, with the EQEEL of high-efficiency OSCs typically remaining below 10−2%. This value is considerably lower than that observed in high efficiency inorganic photovoltaic devices. Here, we report that EQEEL is also influenced by the dissociation rate constant of singlet states (kDS). Importantly, in contrast to the traditional belief that advocates maximizing kDS for superior photovoltaic quantum efficiency (EQEPV), a controlled reduction in kDS is shown to enhance EQEEL without compromising EQEPV. Consequently, a promising experimental approach to address the VNR challenge is proposed, resulting in a significant improvement in the performance of OSCs.

Suppressing Element Inhomogeneity Enables 14.9% Efficiency CZTSSe Solar Cells.

Kesterites, Cu2ZnSn(SxSe1- x)4 (CZTSSe), solar cells suffer from severe open-circuit voltage (VOC) loss due to the numerous secondary phases and defects. The prevailing notion attributes this issue to Sn-loss during the selenization. However, this work unveils that, instead of Sn-loss, elemental inhomogeneity caused by Cu-directional diffusion toward Mo(S,Se)2 layer is the critical factor in the formation of secondary phases and defects. This diffusion decreases the Cu/(Zn+Sn) ratio to 53% at the bottom fine-grain layer, increasing the Sn-/Zn-related bulk defects. By suppressing the Cu-directional diffusion with a blocking layer, the crystal quality is effectively improved and the defect density is reduced, leading to a remarkable photovoltaic coversion efficiency (PCE) of 14.9% with a VOC of 576mV and a certified efficiency of 14.6%. The findings provide insights into element inhomogeneity, holding significant potential to advance the development of CZTSSe solar cells.

Drug Solubility Prediction: A Comparative Analysis of GNN, MLP, and Traditional Machine Learning Algorithms

The effective development and design of pharmaceuticals hold fundamental importance in the fields of medicine and the pharmaceutical industry. In this process, the accurate prediction of drug molecule solubility is a critical factor influencing the bioavailability, pharmacokinetics, and toxicity of drugs. Traditionally, mathematical equations based on chemical and physical properties have been used for drug solubility prediction. However, in recent years, with the advancement of artificial intelligence and machine learning techniques, new approaches have been developed in this field. This study evaluated different modeling approaches consisting of Graph Neural Networks (GNN), Multilayer Perceptron (MLP), and traditional Machine Learning (ML) algorithms. The Random Forest (RF) model stands out as the optimal performer, manifesting superior efficacy through the attainment of minimal error rates. It attains a Root Mean Square Error (RMSE) value of 1.2145, a Mean Absolute Error (MAE) value of 0.9221, and an R-squared (R2) value of 0.6575. In contrast, GNN model displays comparatively suboptimal performance, as evidenced by an RMSE value of 1.8389, an MAE value of 1.4684, and an R2 value of 0.2147. These values suggest that the predictions of this model contain higher errors compared to other models, and its explanatory power is lower. These findings highlight the performance differences among different modeling approaches in drug solubility prediction. The RF model is shown to be more effective than other methods, while the GNN model performs less effectively. This information provides valuable insights into which model should be preferred in pharmaceutical design and development processes.

Evaluating the influence of Cynodon dactylon on the wave force and wave erosion in the water-level fluctuation zone of the Three Gorges Reservoir Area

Wave erosion is the main erosion type in the water-level fluctuation zone (WLFZ) of the Three Gorges Reservoir Area (TGRA). Despite vegetation can effectively mitigate wave erosion in the WLFZ, its influence on the wave force and wave erosion remains unclear. Therefore, the wave experiments were conducted under 3 Cynodon dactylon coverage rates (0, 30% and 60%) and 9 wave conditions (3 wave heights of 4, 6 and 8 cm combined with 3 wave periods of 1, 2 and 3 s) to analyse the wave force (expressed as the wave pressure on the slope surface and the pore water pressure in the slope) and wave erosion rate, and the factors influencing wave erosion were identified. The results indicated that the wave pressure, pore water pressure and wave erosion rate increased by 19.14%–104.75%, 16.84%–65.04% and 23.33%–91.64%, respectively, as wave height increases. The wave pressure decreased by 1.50%–31.23% followed by an increase by 22.05% to 87.10% with the increase of wave period, whereas the pore water pressure and wave erosion rate decreased by 28.33%–53.59% and 20.46%–63.59%, respectively. However, these quantities decreased by 2.10%–50.84%, 17.06%–40.23% and 17.28%–82.18%, respectively, with the increase of Cynodon dactylon coverage rate. It was also discovered that the pore water pressure and Cynodon dactylon coverage rate attained the highest positive and negative correlation coefficients with the wave erosion rate, respectively. In addition, pore water pressure accumulation is the most critical influence factor on wave erosion, and Cynodon dactylon could effectively reduce the pore water pressure via its roots, thus improving the slope wave erosion resistance. This study could be useful to understand the mechanism of plants on controlling wave erosion and could provide a scientific reference for wave erosion control and the ecological construction in the WLFZ.

Integrative analysis of metabolism subtypes and identification of prognostic metabolism-related genes for glioblastoma.

Increasing evidence has demonstrated that cancer cell metabolism is a critical factor in tumor development and progression; however, its role in glioblastoma (GBM) remains limited. In the present study, we classified GBM into three metabolism subtypes (MC1, MC2, and MC3) through cluster analysis of 153 GBM samples from the RNA-sequencing data of The Cancer Genome Atlas (TCGA) based on 2752 metabolism-related genes (MRGs). We further explored the prognostic value, metabolic signatures, immune infiltration, and immunotherapy sensitivity of the three metabolism subtypes. Moreover, the metabolism scoring model was established to quantify the different metabolic characteristics of the patients. Results showed that MC3, which is associated with a favorable survival outcome, had higher proportions of isocitrate dehydrogenase (IDH) mutations and lower tumor purity and proliferation. The MC1 subtype, which is associated with the worst prognosis, shows a higher number of segments and homologous recombination defects and significantly lower mRNA expression-based stemness index (mRNAsi) and epigenetic-regulation-based mRNAsi. The MC2 subtype has the highest T-cell exclusion score, indicating a high likelihood of immune escape. The results were validated using an independent dataset. Five MRGs (ACSL1, NDUFA2, CYP1B1, SLC11A1, and COX6B1) correlated with survival outcomes were identified based on metabolism-related co-expression module analysis. Laboratory-based validation tests further showed the expression of these MRGs in GBM tissues and how their expression influences cell function. The results provide a reference for developing clinical management approaches and treatments for GBM.

Abstract 279: Iatrogenic immunosuppression emplaces tacrolimus to drive squamous skin cancer progression and influence the microenvironment

Abstract One in thirteen organ transplant recipients (OTRs) develop post-transplant cutaneous squamous cell carcinoma (cSCC), leading to significant morbidity upon disease progression. Although chronic ultraviolet (UV) exposure primarily underlies keratinocyte carcinogenesis, long-term immunosuppression is a critical etiologic risk factor due to reduced systemic surveillance of dysplasia. Calcineurin inhibitors such as tacrolimus are commonly administered to suppress the immune system by blocking T-cell proliferation and preventing donor organ rejection. Contrarily, studies have evinced the off-target effects of immunosuppressives, namely azathioprine and cyclosporine, but not tacrolimus — the most widely used in all immunosuppression. In addition, the preclinical research literature has overlooked the contribution of stromal fibroblasts in the cSCC tumor microenvironment (TME). Hence, we hypothesize that tacrolimus exerts direct carcinogenic effects on keratinocytes and fibroblasts in the skin. We further postulate that tacrolimus enables a tumor-permissive microenvironment by activating dermal fibroblasts to cause aggressive and invasive keratinocyte carcinoma in OTRs. To examine this cellular crosstalk phenomenon, we used human keratinocytes, primary dermal fibroblasts and cSCC cells in mono- and co-cultures to mimic cutaneous and tumor complexities. Next, we assessed the molecular mechanisms utilized by tacrolimus to potentiate tumorigenesis pertinent to cell survival, proliferation and invasion. Herein, we show that tacrolimus promotes cell survival dose-dependently in cSCC cells. We also found that a fibroblast-cSCC spheroid co-culture significantly enhances cell invasion. In a wound-healing migration assay, tacrolimus increased the migratory capacity of normal keratinocytes and cSCC cells. However, cell proliferation remains nebulous due to cyclical dose-response effects in vitro. We then queried whether cell proliferation is affected in vivo using immunodeficient mice, and similar results were observed. We confirmed via immunoblotting that tacrolimus induced elevated expression of proliferation markers at distinct drug concentrations. Altogether, our findings illuminate keratinocyte-stroma interactions and particularly isolate the contributory role of tacrolimus in non-immune mediated cSCC pathogenesis. This knowledge suggests newer immunosuppressives that do not inhibit calcineurin activity may help relieve cutaneous malignancies in transplant recipients. Citation Format: Edwin Kumah, Yash Chhabra, Vania Wang, Agrani Dixit, Ashani Weeraratna, Kristin Bibee. Iatrogenic immunosuppression emplaces tacrolimus to drive squamous skin cancer progression and influence the microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 279.

Disruptive factors of vendor-managed inventory in the manufacturing industry

ABSTRACT Vendor-managed inventory began in the early 1980s when retailers demanded that vendors accept responsibility for replenishment based on the retailer’s sales data. Hence, this study identified and examined the critical factor of VMI’s success in the manufacturing industry. 252 valid responses were collected from the manufacturers using a non-probability purposive sampling approach, later analysed using Smart PLS-SEM. The study’s results indicated that information quality has a significant positive effect on VMI success. Similarly, information sharing also has a significant positive effect on VMI. Joint planning also has a significant positive effect on VMI success. Lastly, relationship quality and resource sharing also positively affect VMI’s success. The supplier should be represented in a cross-functional committee tasked with developing proposals and feedback for the system’s continual development. This helps VMI decision-makers avoid a strong buyer viewpoint. Further, the findings of this study give new information to policymakers and SC professionals to understand the optimisation of replenishment choices between the buyer and the supplier.

Identification of Quality Markers in Schisandra chinensis (Turcz.) Baill. Using UPLC-Q-Extractive Orbitrap/MS, Chemometric Analysis, and Network Pharmacology

Chemical composition is a critical factor for determining the efficacy of any traditional Chinese medicine (TCM) and can be used as an indicator of commercial quality. To develop a new strategy for discovering potential quality markers (Q-markers) of TCM by integrating ultra-performance liquid chromatography-Q-extractive orbitrap/mass spectrometry (UPLC-Q-Extractive Orbitrap/MS), chemometric analysis, and network pharmacology, using Schisandra chinensis (Turcz.) Baill. (S. chinensis) as an example. The chemical profiling of S. chinensis was performed using UPLC-Q-Extractive Orbitrap/MS, followed by identification of hepatoprotective Q-markers through a comprehensive understanding of chemometric analysis and virtual target prediction of network pharmacology. Six compounds were considered potent candidates for Q-markers, which were identified as schisandrol A (6), angeloylgomisin H (10), schisantherin A (17), schisantherin B (18), schisandrin A (23), and schisandrin C (26). All Q-markers exhibited significant hepatoprotective activity, as evidenced by in vitro experiments. Subsequently, a method for simultaneous quantification was established and employed to analyse seven batches of S. chinensis. Therefore, the integrated approach of UPLC-Q-Extractive Orbitrap/MS, chemometrics, and network pharmacology proved to be an effective strategy for the discovery of Q-markers that can assist in assessing the overall chemical consistency of samples and provide a basis for quality evaluation of the material basis of S. chinensis.

The interpretation of animate nouns in child and adult Mandarin: from the Universal Grinder to syntactic structure

Abstract Using animate nouns to refer to entities in the world involves a complex interaction of ontology, cognition and language. The present study evaluates two accounts of the use of animate nouns, with Mandarin Chinese as the vehicle for testing between the competing accounts. One account was proposed by Cheng et al. (2008. How universal is the Universal Grinder? In Marjo van Koppen & Bert Botma (eds.), Linguistics in the Netherlands, 50–62. Amsterdam & Philadelphia: John Benjamins). These researchers contend that the count interpretation is basic for Mandarin animate nouns, due to a lexical blocking effect. To access the alternative, mass interpretation requires some kind of pragmatic coercion. A second account was proposed by Pelletier, based on English (1975. Non-Singular reference: Some preliminaries. Philosophia 5(4). 451–465; 2012. Lexical nouns are both +MASS and +COUNT, but they are neither +MASS nor + COUNT. In Diane Massam (ed.), Count and mass across languages, 9–26. Oxford: Oxford University Press). We extend this account to Mandarin animate nouns, proposing that they are encoded in the mental lexicon with both a count sense and a mass sense. To adjudicate between the accounts, we conducted four experiments that were designed to assess the interpretation assigned to animate nouns by Mandarin-speaking children and adults. The experimental conditions manipulated both the syntactic structures of the sentences and the non-linguistic contexts in which those sentences were presented. The experimental findings support our proposal that both mass and count interpretations of animate nouns are available to children and adults when sentences are presented in contexts that are congruent with these interpretations. The findings also suggest that syntactic structure is an even more critical factor in determining the interpretation that is assigned to animate nouns in Mandarin.

Neutrophil to Lymphocyte Ratio in Patients with Major Depressive Disorder

Introduction: Depression is common mood disorder that is linked to systemic inflammation. The neutrophil-lymphocyte ratio (NLR) is a non-specific inflammatory marker that is inexpensive and easy to measure. Low-grade inflammation occurs in a subgroup of patients with Major Depressive disorder (MDD). Objective: To examine the role of inflammation in the etiology of depression based on the NLR in MDD patients who are undergoing no pharmacological therapy. Methods: This observational study was carried out in the Department of Psychiatry of Jahurul Islam Medical College Hospital (JIMCH), Bajitpur, Kishoregonj between December 2013 and May 2014. Subjects between the ages of 18 and 65 were included in the study that involved 61 subjects with diagnosed MDD, who received no pharmacological therapy of depression within the past 01 month were included in the study, while the control group included 67 healthy subjects with having no psychiatric disease. A sociodemographic information form and a Beck Depression Scale were administered, and the blood was taken for biochemical analysis and complete blood parameters were evaluated in the hematology laboratory of JIMCH. All data were expressed as mean±SD. For statistical analysis, Chi-square test (χ2) was used to compare categorical variables, frequencies, and ratios. An independent sample ‘t’ test was used to compare normally distributed variables between two groups. Results: In the present study, we found Significance difference in the NLR, neutrophil count, lymphocyte percentage and leukocyte values of the patient group when compared with control group (P<0.05). Conclusion: The study reveals that NLR tends to be higher in patients with MDD, and a high NLR value supports the view that inflammation is a critical factor in the etiology of MDD. JAFMC Bangladesh. Vol 19, No 1 (June) 2023: 72-75

The Application of Environmental, Social and Governance Standards in Operational Risk Management in SSC in Poland

Organizations are facing increasing pressure to be transparent about their performance and to accept responsibility for their impacts on both society and the environment. The role of ESG is essential from a reporting standpoint. New regulations are forcing organizations to focus more on cascading ESG risk management in order to ensure that the various ESG objectives are analyzed and monitored at the group and subsidiary levels. This article employed the results of an empirical study conducted on risk management concerning shared service centers in Poland. In addition, a case study was conducted based on their internal reports and financial statements. At this stage, SSCs are focusing solely on financial risks and are ignoring the broader perspective. Thus, the promotion of ESG practices in organizations currently represents the most critical factor. ESG-related activities should be cascaded to company subsidiaries, especially those that employ internally separated processes, operate globally and are responsible for end-to-end processes. Based on an analysis of financial statements, few entities currently even consider operational risks, including ESG-related risks. Companies should re-examine their internal governance approach so as to ensure the effective cascading of ESG objectives to the lower levels of the organizational structure.

Effect of urbanization on groundwater resources hydrodynamics and bearing capacity: a case study from the Bayraklı region, İzmir, Türkiye

The bearing capacity of soil is a critical factor in the design of foundations for civil engineering structures. The bearing capacity depends on soil properties, as well as the location of the water table. A rise in the groundwater level can be dramatic, especially in highly urbanized regions, and can affect the bearing capacity of foundations. In this study, groundwater-level fluctuations in a highly urbanized region in İzmir, the third largest city in Türkiye, was monitored over a 1 year period, and its effect on reducing the bearing capacity, which is not considered in foundation design and construction, was investigated. For this purpose, four observation wells equipped with groundwater data loggers were used to determine the variations in groundwater level over 1 year. Using the Terzaghi approach to calculate the bearing capacity, normalized bearing capacity plots for various foundation width/depth ( B / D f ) ratios were generated for all four observation wells. Remarkable bearing capacity changes of 10.94, 8.21, 7.62 and 9.29% were observed in four different observation wells (OW-1, OW-3, OW-6 and OW-9, respectively). The study showed that changes in groundwater level in the region caused by urbanization poses a potential risk to the sustainability of previously constructed foundations.

Mechanistic Insights and Potential Therapeutic Implications of NRF2 in Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a complication of diabetes, especially type 2 diabetes (T2D), characterized by damage in the central nervous system and cognitive impairment, which has gained global attention. Despite the extensive research aimed at enhancing our understanding of DE, the underlying mechanism of occurrence and development of DE has not been established. Mounting evidence has demonstrated a close correlation between DE and various factors, such as Alzheimer's disease-like pathological changes, insulin resistance, inflammation, and oxidative stress. Of interest, nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor with antioxidant properties that is crucial in maintaining redox homeostasis and regulating inflammatory responses. The activation and regulatory mechanisms of NRF2 are a relatively complex process. NRF2 is involved in the regulation of multiple metabolic pathways and confers neuroprotective functions. Multiple studies have provided evidence demonstrating the significant involvement of NRF2 as a critical transcription factor in the progression of DE. Additionally, various molecules capable of activating NRF2 expression have shown potential in ameliorating DE. Therefore, it is intriguing to consider NRF2 as a potential target for the treatment of DE. In this review, we aim to shed light on the role and the possible underlying mechanism of NRF2 in DE. Furthermore, we provide an overview of the current research landscape and address the challenges associated with using NRF2 activators as potential treatment options for DE.

New aspects of femtosecond laser ablation of Si in water: a material perspective

We report a study of the role of material’s conductivity in determining the morphology of nanoparticles and nanostructures produced by ultrafast laser ablation of solids. Nanoparticles and textured surfaces formed by laser ablation display a wide variation in size and morphology depending on the material. In general, these qualities can be grouped as to material type, insulator, semiconductor, or metal; although each has many other different material properties that make it difficult to identify the critical material factor. In this report, we study these nanoparticle/surface structural characteristics as a function of silicon (Si) resistivity, thus honing-in on this critical parameter and its effects. The results show variations in morphology, optical, and nonlinear properties of Si nanoparticles. The yield of colloidal Si nanoparticles increased with an increase in the conductivity of Si. Laser-induced periodic surface structures formed on ablated substrates are also found to be sensitive to the initial conductivity of the material. Further, the laser ablation of Gamma-irradiated Si has been investigated to verify the influence of altered conductivity on the formation of Si nanoparticles. These observations are interpreted using the basic mechanisms of the laser ablation process in a liquid and its intricate relation with the initial density of states and thermal conductivities of the target material.

Eco-evolutionary evidence for the global diversity pattern of Cycas (Cycadaceae).

The evolution of the latitudinal diversity gradient (LDG), characterized by a peak in diversity toward the tropics, has captured significant attention in evolutionary biology and ecology. However, the inverse LDG (i-LDG) mechanism, wherein species richness increases toward the poles, remains inadequately explored. Cycads are among one of the oldest lineages of extant seed plants and have undergone extensive diversification in the tropics. Intriguingly, the extant cycad abundance exhibits an i-LDG pattern, and the underlying causes for this phenomenon remain largely elusive. Here, using 1,843 nuclear genes from a nearly complete sampling, we conducted comprehensive phylogenomic analyses to establish a robust species-level phylogeny for Cycas, the largest genus within cycads. We then reconstructed the spatial-temporal dynamics and integrated global environmental data to evaluate the roles of species ages, diversification rates, contemporary environment, and conservatism to ancestral niches in shaping the i-LDG pattern. We found Cycas experienced decreased diversification rates, coupled with the cooling temperature since its origin in the Eocene from continental Asia. Different regions have distinctively contributed to the formation of i-LDG for Cycas, with the northern hemisphere acting as evolutionary museums and the southern hemisphere serving as cradles. Moreover, water-related climate variables, specifically precipitation seasonality and potential evapotranspiration, were identified as paramount factors constraining Cycas species richness in the rainforest biome near the equator. Notably, the adherence to ancestral monsoonal climates emerges as a critical factor in sustaining the diversity pattern. This study underscores the imperative of integrating both evolutionary and ecological approaches to comprehensively unravel the mechanisms underpinning global biodiversity patterns.

Desulfovibrio desulfuricans and its derived metabolites confer resistance to FOLFOX through METTL3

Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. In comparison, Desulfovibrio was more abundant in the NCB group. Invivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).