Intrinsic Regulators of Actomyosin Contractility Engendering Pulsatile Behaviors

Actomyosin contractility regulates various biological processes including cell migration, muscle contraction, and tissue morphogenesis. Cell cortex underlying a membrane, which is a representative actomyosin network in eukaryote cells, exhibits dynamic contractile behaviors. Interestingly, the cell cortex shows reversible aggregation of actin and myosin called pulsatile contraction in diverse cellular phenomena, such as embryogenesis and tissue morphogenesis. While contractile behaviors have been studied in several in vitro experiments and computational studies, none of them demonstrated the pulsatile contraction of actomyosin networks observed in vivo. Here, we used an agent-based computational model based on Brownian dynamics to identify factors facilitating the pulsatile contraction of actomyosin networks. We first tested effects of several important parameters on the morphology, stress generation, and dynamic properties of actomyosin networks in order to understand how they regulate contraction of actomyosin networks. We found that the pulsatile contraction only occurs when there is a subtle balance between force generation from motors, force relaxation via actin turnover, and force sustainment via network connectivity. Our study provides critical insights into understanding the mechanisms and roles of the pulsatile contraction in cells

Higher-Order Weakly Generalized Epiderivatives and Applications to Optimality Conditions

The notions of higher-order weakly generalized contingent epiderivative and higher-order weakly generalized adjacent epiderivative for set-valued maps are proposed. By virtue of the higher-order weakly generalized contingent (adjacent) epiderivatives, both necessary and sufficient optimality conditions are obtained for Henig efficient solutions to a set-valued optimization problem whose constraint set is determined by a set-valued map. The imposed assumptions are relaxed in comparison with those of recent results in the literature. Examples are provided to show some advantages of our notions and results

Research Progress of the International Carbon Tariff: A Review

Under the constraints of the target peak carbon dioxide emissions and carbon neutrality, how the international carbon tariff can be levied have become an important question for scholars and research institutions all over the world. This paper aimed to comprehensively sort the relevant literature on the Carbon Border Adjustment Mechanism from an economic perspective. Based on defining the concept connotation and extension of carbon tariff, we summarized and determined the price mechanism, institutional mechanism, and coordination mechanism of the carbon tariff, and analyzed the impact of carbon tariff on the economic environment and other fields. Further, this paper makes an international comparison of the existing reasonably operable carbon tariff, points out the focus and direction of the next research, and strives to provide valuable experience and theoretical reference for the innovative practice of building the international Carbon Border Adjustment Mechanism. Keywords: carbon tariff, border tax adjustment, connotation and extension, mechanism design, economic impac

Higher-Order Weakly Generalized Epiderivatives and Applications to Optimality Conditions

The notions of higher-order weakly generalized contingent epiderivative and higher-order weakly generalized adjacent epiderivative for set-valued maps are proposed. By virtue of the higher-order weakly generalized contingent adjacent epiderivatives, both necessary and sufficient optimality conditions are obtained for Henig efficient solutions to a set-valued optimization problem whose constraint set is determined by a set-valued map. The imposed assumptions are relaxed in comparison with those of recent results in the literature. Examples are provided to show some advantages of our notions and results

Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1β Mechanism

Diabetes mellitus is an established risk factor associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Sustained activation of Nod-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to the persistent inflammation and impaired cutaneous wound healing in diabetic mice and human. We have recently demonstrated a compelling linkage between M1 macrophages and BRONJ conditions in both murine and human diseases. The aim of this study was to determine whether NLRP3 inflammasome activation is involved in BRONJ development in diabetic mice. We showed an increased incidence of delayed oral wound healing and bone necrosis of extraction sockets in db/db mice compared with those in nondiabetic db/+ controls, which correlated with an elevated expression of NLRP3, caspase-1, and IL-1β in macrophages residing at local wounds. Constitutively, bone marrow-derived macrophages from db/db mice (db/db BMDMs) secrete a relatively higher level of IL-1β than those from db/+ mice (db/+ BMDMs). Upon stimulation by NLRP3 activators, the secretion of IL-1β by db/db BMDMs was 1.77-fold higher than that by db/+ BMDMs (p \u3c 0.001). Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1β secretion by db/+ and db/db BMDMs, respectively, compared with BMDMs derived from nontreated mice (p \u3c 0.001). Importantly, systemic administration of pharmacological inhibitors of NLRP3 activation improved oral wound healing and suppressed BRONJ formation in db/db mice. Mechanistically, we showed that supplementation with intermediate metabolites of the mevalonate pathway, inhibitors of caspase-1 and NLRP3 activation, an antagonist for P2X7R, or a scavenger of reactive oxygen species (ROS), robustly abolished Zol-enhanced IL-1β release from macrophages in response to NLRP3 activation (p \u3c 0.001). Our findings suggest that diabetes-associated chronic inflammatory response may have contributed to impaired socket wound healing and rendered oral wound susceptible to the development of BRONJ via NLRP3 activation in macrophages. © 2015 American Society for Bone and Mineral Research

Use of surface modified porous membranes for fluid distillation

In some embodiments, the present disclosure pertains to systems and methods for distilling a fluid by exposing the fluid to a porous membrane that includes a surface capable of generating heat. In some embodiments, the heat generated at the surface propagates the distilling of the fluid by converting the fluid to a vapor that flows through the porous membrane and condenses to a distillate. In some embodiments, the surface capable of generating heat is associated with a photo-thermal composition that generates the heat at the surface by converting light energy from a light source to thermal energy. In some embodiments, the photo-thermal composition includes, without limitation, noble metals, semiconducting materials, dielectric materials, carbon-based materials, composite materials, nanocomposite materials, nanoparticles, hydrophilic materials, polymers, fibers, meshes, fiber meshes, hydrogels, hydrogel meshes, nanomaterials, and combinations thereof. Further embodiments pertain to methods of making the porous membranes of the present disclosure

Tfp1 is required for ion homeostasis, fluconazole resistance and N-Acetylglucosamine utilization in Candida albicans

AbstractThe vacuolar-type H+-ATPase (V-ATPase) is crucial for the maintenance of ion homeostasis. Dysregulation of ion homeostasis affects various aspects of cellular processes. However, the importance of V-ATPase in Candida albicans is not totally clear. In this study, we demonstrated the essential roles of V-ATPase through Tfp1, a putative V-ATPase subunit. Deletion of TFP1 led to generation of an iron starvation signal and reduced total iron content, which was associated with mislocalization of Fet34p that was finally due to disorders in copper homeostasis. Furthermore, the tfp1∆/∆ mutant exhibited weaker growth and lower aconitase activity on nonfermentable carbon sources, and iron or copper addition partially rescued the growth defect. In addition, the tfp1∆/∆ mutant also showed elevated cytosolic calcium levels in normal or low calcium medium that were relevant to calcium release from vacuole. Kinetics of cytosolic calcium response to an alkaline pulse and VCX1 (VCX1 encodes a putative vacuolar Ca2+/H+ exchanger) overexpression assays indicated that the cytosolic calcium status was in relation to Vcx1 activity. Spot assay and concentration-kill curve demonstrated that the tfp1∆/∆ mutant was hypersensitive to fluconazole, which was attributed to reduced ergosterol biosynthesis and CDR1 efflux pump activity, and iron/calcium dysregulation. Interestingly, carbon source utilization tests found the tfp1∆/∆ mutant was defective for growth on N-Acetylglucosamine (GlcNAc) plate, which was associated with ATP depletion due to the decreased ability to catabolize GlcNAc. Taken together, our study gives new insights into functions of Tfp1, and provides the potential to better exploit V-ATPase as an antifungal target

Global research trends of diabetes remission: a bibliometric study

BackgroundResearch on diabetes remission has garnered prominence in recent years. However, to date, no pertinent bibliometric study has been published. This study sought to elucidate the current landscape and pinpoint potential new research directions through a bibliometric analysis of diabetes remission.MethodsWe perused relevant articles on diabetes remission from January 1, 2000, to April 16, 2023, in the Web of Science. We utilized CiteSpace software and VOSviewer software to construct knowledge maps and undertake analysis of countries, institutional affiliations, author contributions, journals, and keywords. This analysis facilitated the identification of current research foci and forecasting future trends.ResultsA total of 970 English articles were procured, and the annual publication volume manifested a steady growth trend. Most of the articles originated from America (n=342, 35.26%), succeeded by China and England. Pertaining to institutions, the University of Newcastle in England proliferated the most articles (n=36, 3.71%). Taylor R authored the most articles (n=35, 3.61%), and his articles were also the most co-cited (n=1756 times). Obesity Surgery dominated in terms of published articles (n=81, 8.35%). “Bariatric surgery” was the most prevalently used keyword. The keyword-clustering map revealed that the research predominantly centered on diabetes remission, type 1 diabetes, bariatric surgery, and lifestyle interventions. The keyword emergence and keyword time-zone maps depicted hotspots and shifts in the domain of diabetes remission. Initially, the hotspots were primarily fundamental experiments probing the feasibilities and mechanisms of diabetes remission, such as transplantation. Over the course, the research trajectory transitioned from basic to clinical concerning diabetes remission through bariatric surgery, lifestyle interventions, and alternative strategies.ConclusionOver the preceding 20 years, the domain of diabetes remission has flourished globally. Bariatric surgery and lifestyle interventions bestow unique advantages for diabetes remission. Via the maps, the developmental milieu, research foci, and avant-garde trends in this domain are cogently portrayed, offering guidance for scholars

Follow-up of patients with COVID-19 by the Delta variant after hospital discharge in Guangzhou, Guandong, China

The B.1.617.2 (Delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to a new increment in cases across the globe. We conducted a prospective follow-up of COVID-19 cases to explore the recurrence and potential propagation risk of the Delta variant and discuss potential explanations for the infection recurrence. A prospective, non-interventional follow-up of discharged patients who had SARS-CoV-2 infections by the Delta variant in Guangdong, China, from May 2021 to June 2021 was conducted. The subjects were asked to complete a physical health examination and undergo nucleic acid testing and antibody detection for the laboratory diagnosis of COVID-19. In total, 20.33% (25/123) of patients exhibited recurrent positive results after discharge. All patients with infection recurrence were asymptomatic and showed no abnormalities in the pulmonary computed tomography. The time from discharge to the recurrent positive testing was usually between 1-33 days, with a mean time of 9.36 days. The cycle threshold from the real-time polymerase chain reaction assay that detected the recurrence of positivity ranged from 27.48 to 39.00, with an average of 35.30. The proportion of vaccination in the non-recurrent group was higher than that in the recurrently positive group (26% vs. 4%; χ2 = 7.902; P < 0.05). Two months after discharge, the most common symptom was hair loss and 59.6% of patients had no long-term symptoms at all. It is possible for the Delta variant SARS-CoV-2 patients after discharge to show recurrent positive results of nucleic acid detection; however, there is a low risk of continuous community transmission. Both, the physical and mental quality of life of discharged patients were significantly affected. Our results suggest that it makes sense to implement mass vaccination against the Delta variant of SARS-CoV-2