Distinct Effects Research Articles

Distinct resting-state effective connectivity of large-scale networks in first-episode and recurrent major depression disorder: evidence from the REST-meta-MDD consortium.

Previous studies have shown disrupted effective connectivity in the large-scale brain networks of individuals with major depressive disorder (MDD). However, it is unclear whether these changes differ between first-episode drug-naive MDD (FEDN-MDD) and recurrent MDD (R-MDD). This study utilized resting-state fMRI data from 17 sites in the Chinese REST-meta-MDD project, consisting of 839 patients with MDD and 788 normal controls (NCs). All data was preprocessed using a standardized protocol. Then, we performed a granger causality analysis to calculate the effectivity connectivity (EC) within and between brain networks for each participant, and compared the differences between the groups. Our findings revealed that R-MDD exhibited increased EC in the fronto-parietal network (FPN) and decreased EC in the cerebellum network, while FEDN-MDD demonstrated increased EC from the sensorimotor network (SMN) to the FPN compared with the NCs. Importantly, the two MDD subgroups displayed significant differences in EC within the FPN and between the SMN and visual network. Moreover, the EC from the cingulo-opercular network to the SMN showed a significant negative correlation with the Hamilton Rating Scale for Depression (HAMD) score in the FEDN-MDD group. These findings suggest that first-episode and recurrent MDD have distinct effects on the effective connectivity in large-scale brain networks, which could be potential neural mechanisms underlying their different clinical manifestations.

Nonequilibrium Ab Initio Molecular Dynamics Simulation of Water Splitting at Fe2O3-Hematite/Water Interfaces in an External Electric Field.

In the exploration of the optimal material for achieving the photoelectrochemical dissociation of water into hydrogen, hematite (α-Fe2O3) emerges as a highly promising candidate for proof-of-concept demonstrations. Recent studies suggest that the concurrent application of external electric fields could enhance the photoelectrochemical (PEC) process. To delve into this, we conducted nonequilibrium ab initio molecular dynamics (NE-AIMD) simulations in this study, focusing on hematite-water interfaces at room temperature under progressively stronger electric fields. Our findings reveal intriguing evidence of water molecule adsorption and dissociation, as evidenced by an analysis of the structural properties of the hydrated layered surface of the hematite-water interface. Additionally, we scrutinized intermolecular structures using radial distribution functions (RDFs) to explore the interaction between the hematite slab and water. Notably, the presence of a Grotthuss hopping mechanism became apparent as the electric field strength increased. A comprehensive discussion based on intramolecular geometry highlighted aspects such as hydrogen-bond lengths, H-bond angles, average H-bond numbers, and the observed correlation existing among the hydrogen-bond strength, bond-dissociation energy, and H-bond lifetime. Furthermore, we assessed the impact of electric fields on the librational, bending, and stretching modes of hydrogen atoms in water by calculating the vibrational density of states (VDOS). This analysis revealed distinct field effects for the three characteristic band modes, both in the bulk region and at the hematite-water interface. We also evaluated the charge density of active elements at the aqueous hematite surface, delving into field-induced electronic charge-density variations through the Hirshfeld charge density analysis of atomic elements. Throughout this work, we drew clear distinctions between parallel and antiparallel field alignments at the hematite-water interface, aiming to elucidate crucial differences in local behavior for each surface direction of the hematite-water interface.

Petrogenesis of Oligocene Granitoids and its Implications on Beryllium Mineralization at Pagele, Nianqingtanggula Mountain (Central Tibet)

AbstractThe newly discovered Oligocene granitoids (33.1–28.7 Ma) at Pagele are magmatic rocks related to beryllium mineralization during the India‐Asia late‐collisional stage. This discovery provides an ideal example to study the late‐collisional orogeny and beryllium prospecting in the Lhasa terrane. The Oligocene granitoids include porphyritic granodiorite, Stage I, II and III granites, and granitic pegmatite. Geochemical analysis shows that the porphyritic granodiorite is characterized by high SiO2, K2O, total ΣREE contents, and (La/Yb)N ratios; while the latter two by higher SiO2, lower ΣREE and (La/Yb)N ratios. Notably, the granitic pegmatite has extremely high Y/Ho, low K/Rb and Zr/Hf, and distinct REE tetrad effect (1.14–1.21). This study suggests that the porphyritic granodiorite may be derived from partial melting of beryllium‐rich materials composed of Lhasa ancient crust (70–80%) and enriched Lhasa lithospheric mantle (20–30%) under the tearing subduction of Indian slab. The three‐stage granites and granitic pegmatite, which contain higher beryllium contents or beryls, were likely generated by highly fractionation of the porphyritic granodioritic magma or other homologous magma. Considering the possible genetic and spatial link between Indian slab tear and rifts, we suggest that highly‐fractionated granites in rifting systems represent important Be prospecting targets in the Lhasa terrane.

Effect of supercritical nitrogen content on the weld lines and mechanical properties of microcellular injection molded double gate PP/Al parts

AbstractInjection molding products made of aluminum flakes and polymer blends exhibit a distinctive esthetic effect. However, during the filling process, the melt flows in different directions converge and collide, resulting in the flop effect of the aluminum flake and consequent weld line formation. Herein, microcellular injection molding (MIM) was employed to fabricate polypropylene/aluminum flakes (PP/Al) composite foamed parts with distinct weld lines using supercritical nitrogen (scN2) as the physical blowing agent. The scN2 content has a significant effect on cell diameter and cell density. When the scN2 content was 0.6%, the weld line width of the foamed part was 13.03 μm, while it was 30.41 μm for the solid counterpart due to the expansion and rupture of cells in the flow front during filling. Moreover, the orientation of Al flakes was mostly along the flow direction for the foamed parts, while it was generally aligned perpendicular to the flow direction for solid parts in the weld line region. In addition, the flexural modulus of foamed parts was increased by 29% compared with the solid parts, although the tensile strength was reduced by 18% due to the alignment of Al flakes and the stress concentration on the cell walls. Therefore, this work provides insight into the improvement of flexural property and the mitigation of weld lines for injection molded composite parts using MIM.

Arresting calcium-regulated sperm metabolic dynamics enables prolonged fertility in poultry liquid semen storage

The preservation of liquid semen is pivotal for both industrial livestock production and genetic management/conservation of species with sperm that are not highly cryo-tolerant. Nevertheless, with regard to poultry semen, even brief in vitro storage periods can lead to a notable decline in fertility, despite the in vivo capacity to maintain fertility for several weeks when within the hen’s sperm storage tubules. For fertility in sperm, intracellular calcium ions ([Ca2+]i) play a key role in signaling towards modifying energy metabolism. While reducing [Ca2+]i has been found to enhance the preservation of sperm fertility in some mammals, the connection between semen fertility and calcium availability in avian sperm has received limited attention. In this study, we demonstrate that the use of extracellular and intracellular calcium chelators in liquid semen extenders, specifically EGTA and EGTA-AM, has distinct effects on prolonging the fertility of chicken sperm. These results were validated through in vivo fertility tests. Mechanistically, the effects observed were linked to coordination of mitochondrial metabolism and ATP catabolism. Despite both calcium chelators inducing hypoxia, they differentially regulated mitochondrial respiration and ATP accumulation. This regulation was closely linked to a bimodal control of dynein ATPase activity; a direct initial activation with reduction in [Ca2+]i, and subsequent suppression by cytoplasmic acidification caused by lactic acid. These findings not only contribute to advancing poultry liquid semen preservation techniques, but also elucidates biologically relevant mechanisms that may underlie storage within the female reproductive tract in birds.

Screening significant properties of macro-fiber composite laminate substrate anisotropy with viscoelastic and thermal considerations at the quasi-static level

A macro-fiber composite (MFC) is a class of smart material actuator that employs piezoceramic fibers to extend or contract under an applied electric field. When embedded on a thin substrate, actuated MFCs induce surface pressure, resulting in out-of-plane motion. Design characteristics of the substrate, such as anisotropy, give rise to unique bend/twist behavior. Previous studies on MFC applications have focused on optimizing patch location in relation to the local design to achieve optimal bend/twist motion. However, the resolution to these approaches is restricted to the design space of the application, presenting an absence in piezoelectric laminate design intuition. This research aims to streamline the initial optimization process by analyzing the significant material properties associated with substrate design. To accomplish this, a viscoelastic piezoelectric plate theory model is developed to accurately capture the displacement behavior of the MFC laminate for any given substrate design. Experimental data is used to validate and refine the model, ensuring it closely represents real-world physics. A 2k fractional factorial design of experiments approach is used to identify significant substrate properties per MFC laminate configuration, assigning each material property a two-level coding system. Three configurations are observed, with each exhibiting distinct significant properties and effects compared to others. Furthermore, the study explores the impact of thermal factors on substrate behavior for these MFC laminates, highlighting how significant properties can be temperature dependent. The contributions to the kinematic response due to substrate property perturbation varies uniquely per material property and MFC laminate configuration. Statistical evidence supports the notion that the hysteretic behavior of a material is unaffected by thermal influences and is solely determined by the elastic constants of the substrate. The maximum remanent hysteretic response is shown to be proportional to the maximum actuation response at near room temperature.

The effects of physiological and injurious hydrostatic pressure on murine ex vivo articular and growth plate cartilage explants: an RNAseq study.

Chondrocytes are continuously exposed to loads placed upon them. Physiological loads are pivotal to the maintenance of articular cartilage health, while abnormal loads contribute to pathological joint degradation. Similarly, the growth plate cartilage is subject to various loads during growth and development. Due to the high-water content of cartilage, hydrostatic pressure is considered one of the main biomechanical influencers on chondrocytes and has been shown to play an important role in the mechano-regulation of cartilage. Herein, we conducted RNAseq analysis of ex vivo hip cap (articular), and metatarsal (growth plate) cartilage cultures subjected to physiological (5 MPa) and injurious (50 MPa) hydrostatic pressure, using the Illumina platform (n = 4 replicates). Several hundreds of genes were shown to be differentially modulated by hydrostatic pressure, with the majority of these changes evidenced in hip cap cartilage cultures (375 significantly upregulated and 322 downregulated in 5 MPa versus control; 1022 upregulated and 724 downregulated in 50 MPa versus control). Conversely, fewer genes were differentially affected by hydrostatic pressure in the metatarsal cultures (5 significantly upregulated and 23 downregulated in 5 MPa versus control; 7 significantly upregulated and 19 downregulated in 50 MPa versus control). Using Gene Ontology annotations for Biological Processes, in the hip cap data we identified a number of pathways that were modulated by both physiological and injurious hydrostatic pressure. Pathways upregulated in response to 50 MPa versus control, included those involved in the generation of precursor metabolites and cellular respiration. Biological processes that were downregulated in this tissue included ossification, connective tissue development, and chondrocyte differentiation. Collectively our data highlights the divergent chondrocyte phenotypes in articular and growth plate cartilage. Further, we show that the magnitude of hydrostatic pressure application has distinct effects on gene expression and biological processes in hip cap cartilage explants. Finally, we identified differential expression of a number of genes that have previously been identified as osteoarthritis risk genes, including Ctsk, and Chadl. Together these data may provide potential genetic targets for future investigations in osteoarthritis research and novel therapeutics.

Using Morphological and Etymological Approaches In Teaching Foreign Language

Etymology is the study of the history of the form of words and, by extension, the origin and evolution of their semantic meaning across time. It is a subfield of historical linguistics, and draws upon comparative semantics, morphology, semiotics, and phonetics. Etymology refers to the origin or derivation of a word.(also known as a lexical change) Etymology is important in teaching because it gives both the teacher and the learner the ability to understand the interconnectedness of history with language. Understanding the interconnectedness of words with each other and the way that words have brought people together and divided them over the centuries has distinctive effects on a pedagogical process. Etymology is the key that unlocks both knowledge and a love of knowledge. Many English learners have their first language as one that is a Latin-based Romance language as Spanish. Many others have a language that is commonly spoken in that is also a Latin-based language. When we teach vocabulary, including the etymology of the word makes it much more likely that our students who are learning English will understand the word better and more quickly. Even students who are not native speakers of a Latin-based language can still benefit from etymology because etymology is the ultimate two-for-one special. When you know one prefix, you probably get access to dozens or even hundreds of applications of that prefix. In this way, etymology becomes somewhat like a master key where, by teaching a single definition we unlock that word, but by teaching the etymology, we unlock many. With etymology, learners start to understand the interconnectedness of language and culture, as well as the interconnectedness of history with language. They had better understand the interconnectedness of words with each other and the way that words have brought people together and divided them over the centuries. Morphology is the study of the internal structure of words and forms a core part of linguistic study today. The term (morphology ) is Greek and is a make-up of morph-meaning “shape, form’”, and –ology which means “ the study of something”. For English teachers, etymology is a threshold concept, alongside its linguistic brother morphology (morphology being the study of forms of words, including prefixes, root words and suffixes, etc.), Many methodologists and teachers do believe that knowledge of etymology facilitates the guessing, recognizing, understanding, and remembering the meanings of words and that this approach is the very heart of word study. The paper presented the use of morphological and etymological approach in teaching foreign language.

A Josephson junction-coupled neuron with double capacitive membranes

The channel currents have distinct magnetic field effect and any changes of the electromagnetic field or electirc stimulus will change the membrane potential effectively. A feasible neuron model considers the distinct physical characteristic is more suitable to mimic the neural activities accompanying with shift in energy level. A Josephson junction (JJ) is connected to a neural circuit for estimating the effect of external magnetic field and two capacitors are connected via a linear resistor for mimicing the capacitive field beside two sides of the cell membrane. Its equivalent Hamilton energy is calculated to show the relation between firing mode and energy level. Noisy disturbance is imposed to predict the occurrence of coherence resonance, and the biophysical neuron is excited to present higher energy level. This new neuron model can address the field effect and the biophysical property of cell membrane considered as combination of capacitive fields in double capacitors. It can mimic the physical property of outer and inner membranes, and energy exchange across the double membranes explains the energy mechanism in neural activities. Time-varying energy diveristy between capacitive field is crucial for supporting continuous firing activities. The JJ channel discerns slight changes in external magnetic field and regularity is stabilized under coherence resonance in presence of noisy excitation on the membrane or ion channels.

Akkermansia muciniphila - friend or foe in colorectal cancer?

Akkermansia muciniphila is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of A. muciniphila among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing Akkermansia sp. appears as a promising approach to the treatment of metabolic and inflammatory diseases. In particular, a number of studies have focused on the role of A. muciniphila in colorectal cancer. Of note, the results of these studies in mice are contradictory: some reported a protective role of A. muciniphila in colorectal cancer, while others demonstrated that administration of A. muciniphila could aggravate the course of the disease resulting in increased tumor burden. More recent studies suggested the immunomodulatory effect of certain unique surface antigens of A. muciniphila on the intestinal immune system. In this Perspective, we attempt to explain how A. muciniphila contributes to protection against colorectal cancer in some models, while being pathogenic in others. We argue that differences in the experimental protocols of administration of A. muciniphila, as well as viability of bacteria, may significantly affect the results. In addition, we hypothesize that antigens presented by pasteurized bacteria or live A. muciniphila may exert distinct effects on the barrier functions of the gut. Finally, A. muciniphila may reduce the mucin barrier and exerts combined effects with other bacterial species in either promoting or inhibiting cancer development.

Tailored Nanoscale Architectures for White Light Photoelectrochemistry: Zinc Oxide Nanorod-Based Copper Oxide Heterostructures

This study investigates the morphological evolution, optical properties, and photoelectrochemical (PEC) performance of copper-oxide-coated ZnO nanorods under different annealing conditions. Distinct effects of annealing temperature and atmosphere on Cu2O and CuO growth on ZnO nanorods were observed. SEM images revealed the transformation of Cu2O from silk-like to mushroom-like structures, while CuO formed interconnecting nanomaterials. XRD and XPS analyses showed peak shifts and binding energy changes, highlighting structural and electronic modifications induced by annealing. Moreover, PEC measurements demonstrated the superior photoresponse of CuO-coated ZnO nanorods, especially under negative bias, attributed to favorable band structure, charge carrier separation, and annealing stability compared to Cu2O-coated ones. A noteworthy discovery is that ZnO nanorods coated with CuO nanostructures, prepared under air conditions at 400 °C annealing temperature, exhibit exceptional photocurrents. Applying a 0.4 V voltage increases the photocurrent by approximately 10 mA/cm2. The findings provide valuable insights into tailoring metal oxide semiconductor nanostructures for potential applications in diverse areas, including photoelectrochemistry. This study offers practical guidance on modulating nanostructure growth through annealing to enhance performance. The results hold significance for PEC water splitting and have far-reaching impacts on photocatalysis, environmental remediation, and solar cells.

Emotion recognition with multi-modal peripheral physiological signals

IntroductionHealthcare wearables allow researchers to develop various system approaches that recognize and understand the human emotional experience. Previous research has indicated that machine learning classifiers, such as Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Decision Tree (DT), can improve the accuracy of physiological signal analysis and emotion recognition. However, various emotions can have distinct effects on physiological signal alterations. Therefore, solely relying on a single type of physiological signal analysis is insufficient for accurately recognizing and understanding human emotional experiences.MethodsResearch on multi-modal emotion recognition systems (ERS) has commonly gathered physiological signals using expensive devices, which required participants to remain in fixed positions in the lab setting. This limitation restricts the potential for generalizing the ERS technology for peripheral use in daily life. Therefore, considering the convenience of data collection from everyday devices, we propose a multi-modal physiological signals-based ERS based on peripheral signals, utilizing the DEAP database. The physiological signals selected for analysis include photoplethysmography (PPG), galvanic skin response (GSR), and skin temperature (SKT). Signal features were extracted using the “Toolbox for Emotional Feature Extraction from Physiological Signals” (TEAP) library and further analyzed with three classifiers: SVM, KNN, and DT.ResultsThe results showed improved accuracy in the proposed system compared to a single-modal ERS application, which also outperformed current DEAP multi-modal ERS applications.DiscussionThis study sheds light on the potential of combining multi-modal peripheral physiological signals in ERS for ubiquitous applications in daily life, conveniently captured using smart devices.

Effects of Sodium Nanoalginate and Lime on Swelling Properties of Expansive Soils

The findings revealed that the addition of nanoalginate and lime had distinct effects on various soil properties. Specifically, the liquid limit (LL) and plastic limit (PL) decreased when sodium nanoalginate and lime were added, while the plasticity index (PI) and shrinkage limit (SL) increased. Furthermore, the soil classification was altered when sodium alginate and lime were introduced to the control soil. Regarding the standard Proctor test, it was observed that adding sodium nanoalginate increased the maximum dry density and reduced the optimal moisture content, whereas lime had the opposite effect by decreasing the maximum dry density and increasing the optimal moisture content. The free swelling and swelling pressure tests indicated that the incorporation of sodium nanoalginate and lime reduced both free swelling and swelling pressure. The most significant reduction was observed in the sample containing 7% sodium nanoalginate and 5% lime. Additionally, the study highlighted the influence of processing time, showing that an increase in the curing time led to a decrease in free swelling and swelling pressure in samples mixed with 3% sodium nanoalginate and lime. The XRD test showed that adding sodium nanoalginate reduced primary minerals, forming SAH, while lime reduced quartz and calcite, creating CSH. Overall, the results suggest that sodium nanoalginate can be a more environmentally friendly alternative to lime for soil stabilization projects.

Association of HBsAg levels with differential gene expression in NK, CD8 T, and memory B cells in treated patients with chronic HBV

HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity. An optimized 10x Genomics single-cell RNA sequencing workflow was applied to blood samples and liver fine-needle aspirates from 18 patients undergoing tenofovir/entecavir (NUC) treatment for chronic HBV infection. They were categorized based on their HBsAg levels: high (920-12,447 IU/ml) or low (1-100 IU/ml). Cluster frequencies, differential gene expression, and phenotypes were analyzed. In the blood of HBV-infected patients on NUC, the proportion of KLRC2+ "adaptive" natural killer (NK) cells was significantly lower in the HBsAg-high group and, remarkably, both KLRC2+ NK and KLRG1+ CD8 T cells display enrichment of lymphocyte activation-associated gene sets in the HBsAg-low group. High levels of HBsAg were associated with mild immune activation in the liver. However, no suppression of liver-resident CXCR6+ NCAM1+ NK or CXCR6+ CD69+ CD8 T cells was detected, while memory B cells showed signs of activation in both the blood and liver. Among NUC-treated patients, we observed a minimal impact of HBsAg on leukocyte populations in the blood and liver. However, for the first time, we found that HBsAg has distinct effects, restricted to NK-, CD8 T-, and memory B-cell subsets, in the blood and liver. Our findings are highly relevant for current clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. This study provides unique insight into the impact of HBsAg on gene expression levels of immune cell subsets in the blood and liver, particularly in the context of NUC-treated chronic HBV infection. It holds significant relevance for current and future clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. Our findings raise questions about the effectiveness of such treatment strategies and challenge the previously hypothesized immunomodulatory effects of HBsAg on immune responses against HBV.

Performance and parameter optimization design of microchannel heat sink with different cavity and rib combinations

Microchannel heat sinks play a crucial role in dissipating heat in microelectronic systems in computer data centers. To enhance their thermal performance, this study proposes a combined microchannel design consisting of various cavity shapes and straight ribs, and analyzes its heat transfer and flow performance through numerical simulation. The heat transfer characteristics of microchannel heat sink with different straight rib structures are compared. Moreover, the four parameters including the relative length (α), relative width of the cavity (β), relative length of straight ribs (γ) and relative width of straight ribs (λ) are investigated, and the effects of Reynolds number variation on heat sink Nusselt number (Nu), friction coefficient (f) and thermal enhancement efficiency (η) are studied. The optimization process employs an artificial neural network and a multi-objective genetic algorithm to determine the optimal compromise solution and heat sink model, utilizing the Nusselt number and friction coefficient as evaluation indices. The results show that rectangular rounded straight rib is the straight rib structures with the best comprehensive thermal performance, with an average η approximately 9.7 % higher than that of the non-straight ribbed heat sink model. Furthermore, the variation in the four studied parameters yields distinct effects on the Nusselt number, friction coefficient, and thermal enhancement efficiency. Notably, the optimal performance is achieved when Nu = 13.59679 and f = 0.11855, with corresponding parameter values of α = 0.1575, β = 0.3931, γ = 0.0714, and λ = 1.2149. Ultimately, these results provide valuable insights into the structural optimization of microchannel heat sink cavity and straight rib combination models.

Transit-induced socioeconomic ascent and new metro stations in Helsinki Metropolitan Area: Distinct effects on renters, homeowners, and pre-existing housing dwellers

In recent years, transit-oriented developments have been studied from different angles in different countries. Question has been raised whether public investments in transportation trigger the areas nearby to gentrify or even cause the affordability paradox for the low-income households if they cannot afford to live in the accessibility improved areas. This article contributes to the literature of transit-induced neighbourhood change by estimating the short-term causal effect of accessibility improvements on neighbourhoods' household income, share of highly educated individuals, and share of low-income households, separating between renters and residents in the existing and new housing stock. We are using a quasi-experimental study design with propensity score matching and difference-in-differences regression setup to analyse the socioeconomic changes in the areas close to the newly built metro stations. Overall, we identify a positive effect on the share of residents with higher educations, but don't see effects on median household income or share of low-income households. However, on closer examination, we find short-term transit-induced changes for residents in old housing stock, and to some extent for homeowners, but for the renters we don't find significant results. The findings of this article show that short-term transit-induced neighbourhood change occurs in areas where accessibility has improved.

Modified Hu-lu-ba-wan protects diabetic glomerular podocytes via promoting PKM2-mediated mitochondrial dynamic homeostasis

BackgroundMitochondrial dysfunction is implicated in the progression of diabetic kidney disease (DKD). Damaged mitochondria produce excessive reactive oxygen species (ROS) that can cause apoptosis. Mitochondrial dynamics control the quality and function of mitochondria. Targeting mitochondrial dynamics may reduce ROS-induced apoptosis and improve renal injury in DKD. Modified Hu-lu-ba-wan (MHLBW) shows distinct clinical effects on DKD patients, which are related to its role in antioxidant stress modulation. However, the relevant mechanisms of MHLBW have not been clearly explored. PurposeThis study was aimed to evaluate the therapeutic effects of MHLBW on spontaneous DKD mice and clarify the potential mechanisms. MethodsThe main components of MHLBW were identified by HPLC. Using db/db mice as DKD models, we evaluated the therapeutic effects of MHLBW on mice after an 8-week administration. We investigated the molecular mechanism of MHLBW in regulating mitochondrial dynamic homeostasis, podocyte apoptosis, and glomerular damage. After that, computational docking analysis and in vitro experiments were conducted for further mechanism verification. ResultsIntragastric administration of MHLBW for 8 weeks in db/db mice significantly improved glucose metabolism, basement membrane thickening, mesangial expansion, glomerular fibrosis, and podocyte injury. MHLBW can reverse podocyte apoptosis via promoting mitochondrial dynamic homeostasis, which was related to regulating the PKM2/ PGC-1α/Opa1 pathway. Berberine (BBR), one of the components of MHLBW, exhibited preeminent affinity with PKM2 as reflected by computational docking analysis. In cultured podocytes, BBR can also prevent apoptosis by promoting PKM2-mediated mitochondrial dynamic homeostasis. ConclusionOur study demonstrates that MHLBW can treat DKD by inhibiting glomerular damage and podocyte apoptosis through positive regulation of PKM2-mediated mitochondrial dynamic homeostasis. These results may provide a potential strategy against DKD.

Environmental quality and its impact on total fertility rate: an econometric analysis from a new perspective

BackgroundEnvironmental quality significantly affects various aspects of human existence. This study employs ecological footprint as a proxy to assess the impact of environmental quality on the TFR, measured as births per woman. This study investigates the extent to which ecological footprint indicators impact on the TFR in across 31 countries between from 1990 to 2017.MethodsWe gathered data on ecological footprints, specifically carbon, agricultural land, grazing land, forest products, and fisheries, from the Global Footprint Network. Information on the TFR, Human Development Index (HDI), and per capita Gross National Income (GNI) were sourced from the World Bank and the United Nations. We applied static panel and quantile regression models to scrutinize the connection between the ecological footprint and TFR, showing how the former influences the latter.ResultsThe outcomes reveal that, in both fixed and random effects models, factors including HDI, carbon, and fishing grounds exert a negative influence on TFR, all at a significance level of p < 0.01. Conversely, cropland and forest product footprints exhibited a favorable impact on the TFR (p < 0.01). Furthermore, GNI per capita positively affected the TFR in both models, with a p-value of 0.01. Quantiles regression analysis demonstrated that HDI and carbon footprint had a negative impact on TFR across all quantiles. This statistical significance is maintained for all quantiles, although it is only significant for the carbon footprint up to the 60th quantile, at p < 0.01.ConclusionsThis study establishes a negative correlation between specific ecological footprint indicators, such as carbon and fishing grounds, and TFR. Conversely, there was a positive correlation between the footprint of forest products and the TFR. The primary conclusion drawn is that there is heterogeneity in the results regarding the relationship between ecological footprint and TFR. Moreover, the ecological footprint indicators considered in this study did not uniformly influence TFR. Each ecological footprint indicator exhibited distinct effects on the TFR, displaying either positive or negative correlation coefficients. Future research endeavors may delve into how ecological footprints impact other population dynamics, such as mortality and migration.

Carbon and Nutrients from Organic Residues Modulate the Dynamics of Prokaryotic and Fungal Communities.

Inputs of carbon (C) and nutrients from organic residues may select specific microbes and shape the soil microbial community. However, little is known about the abiotic filtering of the same residues with different nutrient concentrations applied to the soil. In our study, we explored how applying organic residue, vinasse, as fertilizer in its natural state (V) versus its concentrated form (CV) impacts soil microbiota. We conducted two field experiments, evaluating soil prokaryotic and fungal communities over 24 and 45 days with vinasse (V or CV) plus N fertilizer. We used 16S rRNA gene and ITS amplicon sequencing. Inorganic N had no significant impact on bacterial and fungal diversity compared to the control. However, the varying concentrations of organic C and nutrients in vinasse significantly influenced the soil microbiome structure, with smaller effects observed for V compared to CV. Prokaryotic and fungal communities were not correlated (co-inertia: RV coefficient = 0.1517, p = 0.9708). Vinasse did not change the total bacterial but increased the total fungal abundance. A higher C input enhanced the prokaryotic but reduced the fungal diversity. Our findings highlight vinasse's role as an abiotic filter shaping soil microbial communities, with distinct effects on prokaryotic and fungal communities. Vinasse primarily selects fast-growing microorganisms, shedding light on the intricate dynamics between organic residues, nutrient concentrations, and soil microbes.

A guide to ERK dynamics, part 2: downstream decoding.

Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address the question of how the ERK pathway exerts distinct and context-specific effects on multiple processes. We discuss how the dynamics of ERK activity induce selective changes in gene expression programs, with insights from both experiments and computational models. With a focus on single-cell biosensor-based studies, we summarize four major functional modes for ERK signaling in tissues: adjusting the size of cell populations, gradient-based patterning, wave propagation of morphological changes, and diversification of cellular gene expression states. These modes of operation are disrupted in cancer and other related diseases and represent potential targets for therapeutic intervention. By understanding the dynamic mechanisms involved in ERK signaling, there is potential for pharmacological strategies that not only simply inhibit ERK, but also restore functional activity patterns and improve disease outcomes.