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Growth laws emerging from studies of cell populations provide essential constraints on the global mechanisms that coordinate cell growth1-3. The foundation of bacterial cell cycle studies relies on two interconnected dogmas that were proposed more than 50 years ago-the Schaechter-Maaloe-Kjeldgaard growth law that relates cell mass to growth rate1 and Donachie's hypothesis of a growth-rate-independent initiation mass4. These dogmas spurred many efforts to understand their molecular bases and physiological consequences5-14. Although they are generally accepted in the fast-growth regime, that is, for doubling times below 1 h, extension of these dogmas to the slow-growth regime has not been consistently achieved. Here, through a quantitative physiological study of Escherichia coli cell cycles over an extensive range of growth rates, we report that neither dogma holds in either the slow- or fast-growth regime. In their stead, linear relations between the cell mass and the rate of chromosome replication-segregation were found across the range of growth rates. These relations led us to propose an integral-threshold model in which the cell cycle is controlled by a licensing process, the rate of which is related in a simple way to chromosomal dynamics. These results provide a quantitative basis for predictive understanding of cell growth-cell cycle relationships.

The advent of planar metalenses, including the super-oscillatory lens (SOL) and the supercritical lens (SCL) with distinctive interference properties, has profoundly impacted on the long-lasting perception of the far-field optical diffraction limit. In spite of its conspicuous success in achieving marvelously small focal spots, the planar metalens still faces tough design and fabrication challenges to realize high focusing efficiency. In this work, we demonstrated a dual-mode laser fabrication technique based on two-photon polymerization for realizing the multilevel phase SCL with focusing efficiency spiking. Synergistically controlling two types of movement trajectory, which is implemented with the piezo stage and the scanning galvo mirror, enables the fabrication of complicated structures with sub-diffraction-limit feature size. By utilizing such advantage, SCLs with discretized multilevel phase configurations are explicitly patterned. The experimental characterization results have shown that a four-level phase SCL can focus light into a sub-diffraction-limit spot with the lateral size of 0.41 λ/NA (NA is the numerical aperture), while achieve the focal spot intensity and the energy concentration ratio in the focal region 7.2 times and 3 times that of the traditional binary amplitude-type SCL with the same optimization conditions, respectively. Our results may release the application obstacles for the sub-diffraction-limit planar metalens and enable major advances in the fields from label-free optical super-resolution imaging to high precision laser fabrication.

NLRP3 inflammasome plays a critical spatiotemporal role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). This study reports a mechanistic insight into noncanonical NLRP3 inflammasome activation in microglia for the effector stage of EAE. Microglia-specific deficiency of ASC (apoptosis-associated speck-like protein containing a C-terminal caspase-activation and recruitment [CARD] domain) attenuated T cell expansion and neutrophil recruitment during EAE pathogenesis. Mechanistically, TLR stimulation led to IRAKM-caspase-8-ASC complex formation, resulting in the activation of caspase-8 and IL-1[beta] release in microglia. Noncanonical inflammasome-derived IL- 1[beta] produced by microglia in the CNS helped to expand the microglia population in an autocrine manner and amplified the production of inflammatory cytokines/chemokines. Furthermore, active caspase-8 was markedly increased in the microglia in the brain tissue from patients with multiple sclerosis. Taken together, our study suggests that microglia-derived IL-1[beta] via noncanonical caspase-8-dependent inflammasome is necessary for microglia to exert their pathogenic role during CNS inflammation., IntroductionNumerous studies indicate that the inflammatory process in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is initiated by T cells that are reactive against myelin (1-6). Importantly, a growing [...]

Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disease with cumulative impacts on multiple systems, exhibiting significant extrapulmonary impacts, and posing a serious public health problem. Skeletal muscle dysfunction is one of the most pronounced extrapulmonary effects in patients with COPD, which severely affects patient prognosis and mortality primarily through reduced productivity resulting from muscle structural and functional alterations. Although the detailed pathogenesis of COPD has not been fully determined, some researchers agree that oxidative stress plays a significant role. Oxidative stress not only catalyzes the progression of pulmonary symptoms but also drives the development of skeletal muscle dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), is a key transcription factor that regulates the antioxidant response and plays an enormous role in combating oxidative stress. In this review, we have summarized current research on oxidative stress damage to COPD skeletal muscle and analyzed the role of Nrf2 in improving skeletal muscle dysfunction in COPD through exercise. The results suggest that oxidative stress drives the occurrence and development of skeletal muscle dysfunction in COPD. Exercise may improve skeletal muscle dysfunction in patients with COPD by promoting the dissociation of Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, inducing sequestosome1(p62) phosphorylation to bind with Keap1 competitively leading to Nrf2 stabilization and improving dynamin-related protein 1-dependent mitochondrial fission. Nrf2 may be a key target for exercise anti-oxidative stress to alleviate skeletal muscle dysfunction in COPD. Graphical abstract [ABSTRACT FROM AUTHOR]

Filtration surgery is commonly performed for glaucoma treatment to reduce intraocular pressure (IOP); however, scarring of the filtering bleb is the main cause of failure. In this study, we evaluated the effects of the chloride channel blocker 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid (NPPB) on scar formation in filtering blebs. A glaucoma filtering surgery model was generated using Sprague–Dawley rats, divided into the control and NPPB groups receiving injections of different NPPB concentrations. The IOP of all rats decreased 1‐day post‐surgery and gradually increased afterward. However, IOP in rats from the NPPB groups recovered more slowly than that of the control group rats. In addition, the area and survival times of filtering blebs in rats from the NPPB groups were substantially larger and longer than those in the control group. Twenty‐eight days after surgery, the protein and mRNA expression of collagen I, fibronectin and α‐smooth muscle actin in the filtering area of rats from the NPPB groups were significantly lower than that in the control group rats. Collectively, our study demonstrates that NPPB inhibits filtering bleb scar formation, maintains filtering bleb morphology and prolongs filtering bleb survival time by inhibiting the differentiation of conjunctival fibroblasts and extracellular matrix synthesis. [ABSTRACT FROM AUTHOR]