Progressive Pulmonary Fibrosis Is Caused by Elevated Mechanical Tension on Alveolar Stem Cells.

Fibrosis can develop in most organs and causes organ failure. The most common type of lung fibrosis is known as idiopathic pulmonary fibrosis, in which fibrosis starts at the lung periphery and then progresses toward the lung center, eventually causing respiratory failure. Little is known about the mechanisms underlying the pathogenesis and periphery-to-center progression of the disease. Here we discovered that loss of Cdc42 function in alveolar stem cells (AT2 cells) causes periphery-to-center progressive lung fibrosis. We further show that Cdc42-null AT2 cells in both post-pneumonectomy and untreated aged mice cannot regenerate new alveoli, resulting in sustained exposure of AT2 cells to elevated mechanical tension. We demonstrate that elevated mechanical tension activates a TGF-ß signaling loop in AT2 cells, which drives the periphery-to-center progression of lung fibrosis. Our study establishes a direct mechanistic link between impaired alveolar regeneration, mechanical tension, and progressive lung fibrosis.

Anatomically distinct fibroblast subsets determine skin autoimmune patterns.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment1-3. Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body4-6. Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8+ T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8+ cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases.

Characterisation of the interplay between microstructure and opto-electronic properties of Cu(In,Ga)S2solar cells by using correlative CL-EBSD measurements.

Cathodoluminescence and electron backscatter diffraction have been applied to exactly the same grain boundaries (GBs) in a Cu(In,Ga)S2solar absorber in order to investigate the influence of microstructure on the radiative recombination behaviour at the GBs. Two different types of GB with different microstructure were analysed in detail: random high angle grain boundaries (RHAGBs) and Σ3 GBs. We found that the radiative recombination at all RHAGBs was inhibited to some extent, whereas at Σ3 GBs three different observations were made: unchanged, hindered, or promoted radiative recombination. These distinct behaviours may be linked to atomic-scale grain boundary structural differences. The majority of GBs also exhibited a small spectral shift of about ±10 meV relative to the local grain interior (GI) and a few of them showed spectral shifts of up to ±40 meV. Red and blue shifts were observed with roughly equal frequency.

Spatiotemporal optical properties of dissolved organic matter in a sluice-controlled coastal plain river with both salinity and trophic gradients.

Due to the combined effect of sluices and sea tide, the sluice-controlled coastal plain river would be characterized by both trophic state and salinity gradients, affecting the spatiotemporal optical properties of dissolved organic matter (DOM). In this study, we investigated the spatiotemporal variation of water quality parameters and optical properties of DOM in the Haihe River, a representative sluice-controlled coastal plain river in Tianjin, China. A significant salinity gradient and four trophic states were observed in the water body of the Haihe River. Two humic- and one protein-like substances were identified from the DOM by the three-dimensional fluorescence spectra combined with the parallel factor (PARAFAC) analysis. Pearson's correlation analysis and redundancy analysis (RDA) showed that the salinity significantly affected the abundance of chromophoric DOM (CDOM) but did not cause significant changes in the fluorescence optical characteristics. In addition, the effect of Trophic state index (TSI) on the CDOM abundance was greater than that on the fluorescence intensity of fluorescent dissolved organic matter (FDOM). In the water body with both salinity and trophic state gradients, TSI posed a greater influence than salinity on the CDOM abundance. Our results fill the research gap in spatiotemporal DOM characteristics and water quality variation in water bodies with both salinity and trophic state gradients. These results are beneficial for clarifying the joint influence of saline intrusion and sluices on the DOM characteristics and water quality in sluice-controlled coastal plain rivers.

Substituent, Solvent, and Dispersion Effects on the Zwitterionic Character and Dimerization Thermochemistry of the Group 6 Fulvene Metal Tricarbonyl Complexes.

Dimerizations of fulvene metal tricarbonyl complexes of the type (C5H4CRR')M(CO)3 (R, R' = MeO, Me, H; M = Cr, Mo, W) to form a metal-metal bond and a new carbon-carbon bond, thereby giving binuclear cyclopentadienyl metal carbonyl derivatives, are predicted to be thermochemically favored but to have significant activation energies ranging from ΔE = 19 to 42 kcal/mol. However, the introduction of dimethylamino but not methoxy substituents onto the exocyclic carbon atom changes the situation drastically so that the monomers [C5H4CH(NMe2)]M(CO)3 and [C5H4C(NMe2)2]M(CO)3 become strongly thermochemically favored, lying ΔE = 43 kcal/mol (M = W) to 63 kcal/mol (M = Cr) below their corresponding dimers. In such dimethylamino-substituted (fulvene)M(CO)3 derivatives, the M-C distance to the exocyclic fulvene carbon is lengthened beyond the bonding distance to give a zwitterionic structure with a pentahapto fulvene ligand. Such M-C distances in (fulvene)M(CO)3 complexes, which have preferred zwitterionic structures, increase with increasing solvent polarity (i.e., dielectric constant) until a saturation point is reached.

Water quality characteristics and assessment of Yongding New River by improved comprehensive water quality identification index based on game theory.

The Yongding New River is essential for the water supplies of Tianjin. To date, there is no comprehensive report that assesses the year-round water quality of the Yongding New River Main stream. Moreover, little attention has been given to determining a combined weight for improving the traditional comprehensive water quality identification index (ICWQII) by the game theory. Seven water quality parameters were investigated monthly along the main stream of the Yongding New River from May 2018 to April 2019. Organic contaminants and nitrogen pollution were mainly caused by point sources pollution, and the total phosphorus mainly by non-point source pollution. Dramatic spatio-temporal variations of water quality parameters were jointly caused by different pollutant sources and hydrometeorological factors. In terms of this study, an improved comprehensive water quality identification index (ICWQII) based on entropy weight or variation coefficient and traditional CWQII underestimated the water qualities, and an ICWQII based on the superstandard multiple method overvalued the assessments. By contrast, water qualities assessments done with an ICWQII based on the game theory matched perfectly with the practical situation. The ICWQII based on game theory proposed in this study takes into account not only the degree of disorder and variation of water quality data, but also the influence of standard-exceeded pollution indicators, whose results are relatively reasonable. All findings and the ICWQII based on game theory can provide scientific support for decisions related to the water environment management of the Yongding New River and other waters.

Comparative Study of the Thermal Stabilities of the Experimentally Known High-Valent Fe(IV) Compounds Fe(1-norbornyl)4 and Fe(cyclohexyl)4.

The high stability of the experimentally known homoleptic 1-norbornyl derivative (nor)4Fe of iron in the unusual +4 oxidation state is a consequence of the high reaction barriers of the singlet or triplet potential surfaces constrained by the global dispersion attraction and the great steric demands of the norbornyl groups. The much more limited stability of the corresponding cyclohexyl derivative (cx)4Fe may result from the conical intersection between the singlet potential surface and the quintet spin potential surface arising from the weaker dispersion attraction and the reduced steric effect of the cyclohexyl groups relative to the 1-norbornyl groups. In contrast, the high stability of the likewise experimentally known (cx)4M (M = Ru or Os) structures results from the larger ligand field splitting (Δ) of the d-orbital energies for the second and third-row transition metals ruthenium and osmium relative to that of the first-row transition metal iron. The cyclohexyl derivative (cx)4Fe is predicted to be reactive toward carbon monoxide to insert CO into up to two Fe-C bonds. However, the dispersion effect as well as the much larger size of the 1-norbornyl substituents prevents similar reactivity of (nor)4Fe with carbon monoxide.

Conservation-Dissipation Formalism for soft matter physics: I. Augmentation to Doi's variational approach.

In the first paper of this series, we prove that by choosing the proper variational function and variables, the variational approach proposed by Doi in soft matter physics is equivalent to the Conservation-Dissipation Formalism. To illustrate the correspondence between these two theories, several novel examples in soft matter physics, including the particle diffusion in dilute solutions, polymer phase separation dynamics and nematic liquid crystal flows, are carefully examined. Based on our work, a deep connection among the generalized Gibbs relation, the second law of thermodynamics and the variational principle in non-equilibrium thermodynamics is revealed.

Conservation-Dissipation Formalism for soft matter physics: II. Application to non-isothermal nematic liquid crystals.

For most existing non-equilibrium theories, the modeling of non-isothermal processes is a hard task. Intrinsic difficulties involve the non-equilibrium temperature, the coexistence of conserved energy and dissipative entropy, etc. In this paper, by taking the non-isothermal flow of nematic liquid crystals as a typical example, we illustrate that thermodynamically consistent models in either vectorial or tensorial forms can be constructed within the framework of the Conservation-Dissipation Formalism (CDF). And the classical isothermal Ericksen-Leslie model and Qian-Sheng model are shown to be special cases of our new vectorial and tensorial models in the isothermal, incompressible and stationary limit. Most importantly, from the above examples, it is known that CDF can easily solve the issues relating with non-isothermal situations in a systematic way. The first and second laws of thermodynamics are satisfied simultaneously. The non-equilibrium temperature is defined self-consistently as a partial derivative of the entropy function. Relaxation-type constitutive relations are constructed, which give rise to classical linear constitutive relations, like Newton's law and Fourier's law, in stationary limits. Therefore, CDF is expected to have a broad scope of applications in soft matter physics, especially under complicated situations, such as non-isothermal, compressible and nanoscale systems.

Dispersion Effects in Stabilizing Organometallic Compounds: Tetra-1-norbornyl Derivatives of the First-Row Transition Metals as Exceptional Examples.

In 1972 Bower and Tennett first synthesized a series of tetra-1-norbornyl derivatives, (nor)4M, of the first-row transition metals from titanium to cobalt. These were found to be exceptionally stable for homoleptic metal alkyls containing only metal-carbon σ-bonds. The theoretical energies for the dissociation of 1-norbornyl ligands from these unusually high oxidation state organometallics through the reactions (nor)4M → (nor)3M + nor• and (nor)4M → (nor)2M + nor-nor indicate that dispersion effects play an important role in determining their exceptional stability. Thus, all of the (nor)4M (M = Ti to Cu) derivatives are viable with respect to 1-norbornyl radical dissociation when the London dispersion effect is considered. However, (nor)4Cu becomes disfavored if the dispersion correction is ignored. Thus, the stability of the (nor)4M molecules is seen to arise from the favorable combination of steric and dispersion force effects of the four 1-norbornyl groups tetrahedrally disposed around the metal atom and maximizing the dispersion attraction between them in a spherical hydrocarbon structure with a central metal atom. The tri-1-norbornyl derivatives (nor)3M appear be disfavored with respect to disproportionation into (nor)4M + (nor)2M. This is consistent with the experimental syntheses of the (nor)4M (M = Cr to Co) derivatives with the metal in the +4 oxidation by reactions with 1-norbornyllithium with metal halides in the +2 or +3 metal oxidation states. Both the OPBE method and the BPW91 method predict high-spin states for the d2 and d3 complexes (nor)4Cr and (nor)4Mn but low-spin states for (nor)4Fe and (nor)4Co, consistent with experiment.

Tuning the Magnetic Anisotropy at a Molecule-Metal Interface.

We demonstrate that a C(60) overlayer enhances the perpendicular magnetic anisotropy of a Co thin film, inducing an inverse spin reorientation transition from in plane to out of plane. The driving force is the (60)/Co interfacial magnetic anisotropy that we have measured quantitatively in situ as a function of the (60) coverage. Comparison with state-of-the-art ab initio calculations show that this interfacial anisotropy mainly arises from the local hybridization between (60) p(z) and Co d(z(2)) orbitals. By generalizing these arguments, we also demonstrate that the hybridization of (60) with a Fe(110) surface decreases the perpendicular magnetic anisotropy. These results open the way to tailor the interfacial magnetic anisotropy in organic-material-ferromagnet systems.

Cell growth and size homeostasis in silico.

Cell growth in size is a complex process coordinated by intrinsic and environmental signals. In a research work performed by a different group, size distributions of an exponentially growing population of mammalian cells were used to infer cell-growth rate in size. The results suggested that cell growth was neither linear nor exponential, but subject to size-dependent regulation. To explain the observed growth pattern, we built a mathematical model in which growth rate was regulated by the relative amount of mRNA and ribosomes in a cell. Under the growth model and a stochastic division rule, we simulated the evolution of a population of cells. Both the sampled growth rate and size distribution from this in silico population agreed well with experimental data. To explore the model space, alternative growth models and division rules were studied. This work may serve as a starting point to understand the mechanisms behind cell growth and size regulation using predictive models.

Identification of 8 candidate microsatellite instability loci in colorectal cancer and validation of the ACVR2A mechanism in the tumor progression.

This study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A's influence on CRC advancement through in vivo tumor experiments and hematoxylin-eosin (HE) staining. Transwell assays gauged ACVR2A's role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC's PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A's influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A's critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.

Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.

Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.

Revolutionizing soil heavy metal remediation: Cutting-edge innovations in plant disposal technology.

Soil contamination with heavy metals has emerged as a global environmental threat, compromising agricultural productivity, ecosystem integrity, and human health. Conventional remediation techniques often fall short due to high costs, operational complexities, and environmental drawbacks. Plant-based disposal technologies, including biochar, phytometallurgy, and phrolysis, have emerged as promising solutions in this regard. Grounded in a novel experimental framework, biochar is studied for its dual role as soil amendment and metal adsorbent, while phytometallurgy is explored for its potential in resource recovery and economic benefits derived from harvested metal-rich plant biomass. Pyrolysis, in turn, is assessed for transforming contaminated biomass into value-added products, thereby minimizing waste. These plant disposal technologies create a circular model of remediation and resource utilization that holds the potential for application in large-scale soil recovery projects, development of environmentally friendly agro-industries, and advancement in sustainable waste management practices. This review mainly discussed cutting-edge plant disposal technologies-biochar application, phytometallurgy, and pyrolysis-as revolutionary approaches to soil heavy metal remediation. The efficacy, cost-effectiveness, and environmental impact of these innovative technologies are especially evaluated in comparison with traditional methods. The success of these applications could signal a paradigm shift in how we approach both environmental remediation and resource recovery, with profound implications for sustainable development and circular economy strategies.

Directed Evolution of Escherichia coli Nissle 1917 to Utilize Allulose as Sole Carbon Source.

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D-allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence-activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme-substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D-allulose in promoting health and well-being.

Investigation of the Solar Hydrogen Sensitivity of GeSe Thin Film Photoelectrode with Photoelectrochemical Environment.

GeSe photovoltaic thin films are very promising for photoelectrochemical (PEC) hydrogen evolution. The GeSe-based PEC water splitting device is a system containing a photoelectrode, electrolyte, and other packages, and the performance of the GeSe photoelectrode inside the system is very sensitive to the PEC system environment, such as the electrolyte temperature, pH, and concentration. Here, we reveal how the electrolyte environment at the electrolyte/photoelectrode interface influences the optoelectronic/PEC properties of GeSe photoelectrodes. It was found that the photocurrent density of the GeSe photoelectrode increased with temperature between 10 and 50 °C but decreased when the temperature was over 50 °C. In addition, the pH values of the electrolyte were inversely proportional to the photocurrent density of the GeSe photoelectrode. Moreover, the PEC performance improved as the sodium ion concentration of the electrolyte increased. The results in this work should provide a new direction for further optimizing the performance of photoelectrodes.

Dexamethasone Does Not Provide Additional Clinical Analgesia Effect to Local Wound Infiltration: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Although the use of dexamethasone as an adjunct agent is associated with alleviating pain and prolonging analgesic duration in local wound infiltration (LWI), efficacy and safety of dexamethasone infiltration have not been fully explored. The study sought to quantify the pooled effects of dexamethasone infiltration on postoperative pain, analgesic consumption, and side effects through a review of randomized controlled trials (RCTs). Approach: RCTs comparing dexamethasone + LWI with LWI alone were retrieved from seven electronic databases. Co-primary outcomes were rest pain scores and cumulative morphine equivalent consumption within 24 h postoperatively. The study followed PRISMA, AMSTAR, and the Cochrane Collaboration. Results: Eight trials comprising 609 patients were included in the final analysis. Results indicated that dexamethasone infiltration effects were only statistical but not clinically significant at individual time points of rest pain and patient satisfaction scores. Notably, the effect of dexamethasone infiltration therapy on other pain-related parameters, including cumulative morphine consumption (mean difference, -9.05 mg; 95% CI: -22.47 to 4.37), was not significantly different compared with the control group. Analysis showed no significant differences in safety indicators between the two groups. The overall quality of evidence was high to very low. Innovation: Although statistically significant effects of dexamethasone infiltration were observed for some outcomes of postoperative wound pain, the overall benefits were below the expected minimal clinically important difference. Conclusions: In summary, the current evidence does not support routine clinical use of dexamethasone in LWI. However, further studies should explore the clinical value of preemptive analgesia and safety of a combination of dexamethasone with ropivacaine for LWI.

STEMI patients receiving percutaneous coronary intervention for a culprit lesion with coronary artery bifurcation-efficacy and safety of the jailed semi-inflated balloon.

Background: We aimed to evaluate the efficacy and safety of the 'jailed semi-inflated balloon technique' (JSIBT) for side branch (SB) protection in STEMI patients with a culprit lesion involving a coronary artery bifurcation while undergoing emergent percutaneous coronary intervention (PCI). Methods: We treated between Jan, 2011 and Jun, 2020, a total of 264 STEMI patients with a culprit lesion that involved a coronary artery bifurcation using primary PCI. In 30 patients, SB was protected by JSIBT (the JSIBT group). In 234 patients, SB was either protected or not protected by a placed wire (the non-JSIBT group). Results: In both groups, after PCI procedure, TIMI flows of main vessel (MV) and SB were increased significantly compared with their measurements before the procedure. TIMI flows of post-procedural MV were similar between the two groups. In the JSIBT group, TIMI flows of SB both peri-procedure and post-procedure measurements were significantly greater than the non-JSIBT group. Despite a higher incidence of SB dissection in the JSIBT group, no inter-group difference was found in their total SB complications (like SB dissection, SB occlusion, wire entrapment or balloon rupture/entrapment). While JSIBT was an independent predictor for the SB TIMI 3 flow measured at the end of primary PCI, it was not an independent predictor for SB complications. Conclusion: The use of JSIBT as a method of SB protection during primary PCI not only provided better SB protection, but it also had a similar rate of SB complications compared with those with or without prior application of SB wire. This technique may be an effective method of protecting SB for STEMI patients involving coronary artery bifurcation and underwent emergent PCI.