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The transcription factor E2F links the RB pathway to the p53 pathway upon loss of function of pRB, thereby playing a pivotal role in the suppression of tumorigenesis. E2F fulfills a major role in cell proliferation by controlling a variety of growth-associated genes. The activity of E2F is controlled by the tumor suppressor pRB, which binds to E2F and actively suppresses target gene expression, thereby restraining cell proliferation. Signaling pathways originating from growth stimulative and growth suppressive signals converge on pRB (the RB pathway) to regulate E2F activity. In most cancers, the function of pRB is compromised by oncogenic mutations, and E2F activity is enhanced, thereby facilitating cell proliferation to promote tumorigenesis. Upon such events, E2F activates the Arf tumor suppressor gene, leading to activation of the tumor suppressor p53 to protect cells from tumorigenesis. ARF inactivates MDM2, which facilitates degradation of p53 through proteasome by ubiquitination (the p53 pathway). P53 suppresses tumorigenesis by inducing cellular senescence or apoptosis. Hence, in almost all cancers, the p53 pathway is also disabled. Here we will introduce the canonical functions of the RB-E2F-p53 pathway first and then the non-classical functions of each component, which may be relevant to cancer biology.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

Background: Malnutrition in cardiovascular disease is associated with poor prognosis, especially in patients with heart failure and acute coronary syndrome (ACS). High bleeding risk is also linked to coronary artery disease prognosis, including ACS. However, whether the extent of malnutrition and high bleeding risk have a cumulative impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention remains unclear. Methods: We analyzed 275 patients with ACS treated with percutaneous coronary intervention. The Controlling Nutritional Status score and Japanese version of the Academic Research Consortium for High Bleeding Risk criteria (J-HBR) were retrospectively evaluated. The primary and secondary outcomes were adjusted using the inverse probability treatment weighting method. Results: The prevalence of moderate or severe malnutrition in this cohort was 16%. Kaplan–Meier analysis showed a significantly higher incidence of major adverse cardiovascular and cerebrovascular events in patients who were moderately or severely malnourished than in those who were not. Notably, the incidence of these major events was similar between severely malnourished patients with J-HBR and those without. Conclusion: Moderate or severe malnutrition has a significant impact on the long-term prognosis of patients with ACS who undergo percutaneous coronary intervention.

Upper: Giant impact (Courtesy NASA/JPL-Caltech); chondrule, majorite in shocked enstatite (Courtesy Miyahara); Lower: Collision of planetesimals (Courtesy NASA/JPL-Caltech); Raman mapping of wadsleyite and ringwoodite in Peace River L6 (Courtesy Miyahara and El Goresy).

Background: Despite endoscopic thyroid surgery contributing to excellent cosmetic outcomes, it requires longer surgical time than open surgery. This study evaluates the factors associated with operative time in video-assisted neck surgery. Methods: We retrospectively reviewed patients who underwent hemithyroidectomy by video-assisted neck surgery at a single hospital between 2017 and 2021. The clinical parameters were evaluated: age, sex, body weight, body mass index, coexistence of Hashimoto thyroiditis, side of operation, surgical approach to thyroid (midline approach or lateral approach), operation time, amount of blood loss during surgery, maximum tumor diameter and tumor volume, and postoperative complications. These parameters were compared to investigate the association of operative time and surgical approach. Results: Seventy consecutive patients were enrolled in this study, the median age at operation was 50 years, and there were 6 (8.6%) men and 64 (91.4%) women. The median body weight and body mass index at operation were 56.6 kg and 21.5, respectively. Coexistence of Hashimoto thyroiditis was found in 17 (24.3%) patients. Significant differences were found between the groups with longer and shorter operation time than median 201 minutes in surgical approaches to the thyroid (P

Developments in Prussian blue analogues (PBAs) have centred solely on their crystalline state. Here, the authors describe the preparation of the glassy state of PBAs via a mechanically induced crystal-to-glass transformation and explore their properties.

Abstract Pancreatic cancer is a highly challenging malignancy with extremely poor prognosis. Cytoglobin (CYGB), a hemeprotein involved in liver fibrosis and cancer development, is expressed in pericytes of all organs. Here, we examined the role of CYGB in the development of pancreatic cancer. CYGB expression appeared predominately in the area surrounding adenocarcinoma and negatively correlated with tumor size in patients with pancreatic cancer. Directly injecting 7, 12-dimethylbenz[a]anthracene into the pancreatic tail in wild-type mice resulted in time-dependent induction of severe pancreatitis, fibrosis, and oxidative damage, which was rescued by Cygb overexpression in transgenic mice. Pancreatic cancer incidence was 93% in wild-type mice but only 55% in transgenic mice. Enhanced CYGB expression in human pancreatic stellate cells in vitro reduced cellular collagen synthesis, inhibited cell activation, increased expression of antioxidant-related genes, and increased CYGB secretion into the medium. Cygb-overexpressing or recombinant human CYGB (rhCYGB) -treated MIA PaCa-2 cancer cells exhibited dose-dependent cell cycle arrest at the G1 phase, diminished cell migration, and reduction in colony formation. RNA sequencing in rhCYGB-treated MIA PaCa-2 cells revealed downregulation of cell cycle and oxidative phosphorylation pathways. An increase in MIA PaCa-2 cell proliferation and reactive oxygen species production by H2O2 challenge was blocked by rhCYGB treatment or Cygb overexpression. PANC-1, OCUP-A2, and BxPC-3 cancer cells showed similar responses to rhCYGB. Known antioxidants N-acetyl cysteine and glutathione also inhibited cancer cell growth. These results demonstrate that CYGB suppresses pancreatic stellate cell activation, pancreatic fibrosis, and tumor growth, suggesting its potential therapeutic application against pancreatic cancer.

Abstract Neumann band in iron meteorites, which is deformation twins in kamacite (Fe–Ni alloy), has been known to be a characteristic texture indicating ancient collisions on parent bodies of meteorites. We conducted a series of shock recovery experiments on bcc iron with the projectile velocity at 1.5 km/s at various initial temperatures, room temperature, 670 K, and 1100 K, and conducted an annealing experiment on the shocked iron. We also conducted numerical simulations with the iSALE-2D code to investigate peak pressure and temperature distributions in the nontransparent targets. The effects of pressure and temperature on the formation and disappearance of the twins (Neumann band) were explored based on laboratory and numerical experiments. The twin was formed in the run products of the experiments conducted at room temperature and 670 K, whereas it was not observed in the run product formed by the impact at 1100 K. The present experiments combined with the numerical simulations revealed that the twin was formed by impacts with various shock pressures from 1.5–2 GPa to around 13 GPa. The twin in iron almost disappeared by annealing at 1070 K. The iron meteorites with Neumann bands were shocked at this pressure range and temperatures at least up to 670 K, and were not heated to the temperatures above 1070 K after the Neumann band formation.

An important question that is being increasingly studied across subdisciplines of Heliophysics is “how do mesoscale phenomena contribute to the global response of the system?” This review paper focuses on this question within two specific but interlinked regions in Near-Earth space: the magnetotail’s transition region to the inner magnetosphere and the ionosphere. There is a concerted effort within the Geospace Environment Modeling (GEM) community to understand the degree to which mesoscale transport in the magnetotail contributes to the global dynamics of magnetic flux transport and dipolarization, particle transport and injections contributing to the storm-time ring current development, and the substorm current wedge. Because the magnetosphere-ionosphere is a tightly coupled system, it is also important to understand how mesoscale transport in the magnetotail impacts auroral precipitation and the global ionospheric system response. Groups within the Coupling, Energetics and Dynamics of Atmospheric Regions Program (CEDAR) community have also been studying how the ionosphere-thermosphere responds to these mesoscale drivers. These specific open questions are part of a larger need to better characterize and quantify mesoscale “messengers” or “conduits” of information—magnetic flux, particle flux, current, and energy—which are key to understanding the global system. After reviewing recent progress and open questions, we suggest datasets that, if developed in the future, will help answer these questions.

IntroductionStroke is one of the most common neurological disorders worldwide. Stroke survivors have restricted activities of daily living (ADL) and lower functional independence measures (FIM) after disease onset. Recovery of postural control abilities in patients with stroke is one of the most important therapeutic goals. In this study, we examined the differences in the FIM motor items between groups that performed postural control exercises with the upper limb and those that performed postural control exercises without the upper limb.MethodsThe medical records of patients with stroke admitted and discharged from the Recovery Rehabilitation Unit at Azumino Red Cross Hospital between 2016 and 2018 were reviewed. We retrospectively investigated the relationships between postural control exercises with or without upper limbs, FIM motor items at admission and discharge, and percentage of gait acquisition at discharge.Results and DiscussionAmong the thirteen FIM motor items, nine (bathing, dressing the upper body, dressing the lower body, toileting, transfers [bed, chair, and wheelchair], transfers [toilet], transfers [tub or shower], locomotion, and climbing of stairs) were significantly different between the two groups (those who performed postural control exercises with the upper limb and those who performed postural control exercises without the upper limb). Patients with stroke who performed postural control exercises without the upper limbs showed a higher percentage of gait acquisition. Touch contact during quiet standing reduces body sway and the associated fluctuations. However, continual practice of postural control with a small degree of body sway for a long period after a stroke would result in decreased pressure on the sole. This may hinder postural control relearning. Touch contact also reduces anticipatory postural adjustment, which may limit the improvement in balance ability during physical exercise. Postural control exercises without the upper limbs improve postural control ability and may be beneficial from a long-term perspective.

Complement is involved in the pathogenesis of neuroimmune disease, but the detailed pathological roles of the complement pathway remain incompletely understood. Recently, eculizumab, a humanized anti-C5 monoclonal antibody, has been clinically applied against neuroimmune diseases such as myasthenia gravis and neuromyelitis optica spectrum disorders (NMOSD). Clinical application of eculizumab is also being investigated for another neuroimmune disease, Guillain-Barré syndrome (GBS). However, while the effectiveness of eculizumab for NMOSD is extremely high in many cases, there are some cases of myasthenia gravis and GBS in which eculizumab has little or no efficacy. Development of effective biomarkers that reflect complement activation in these diseases is therefore important. To identify biomarkers that could predict disease status, we retrospectively analyzed serum levels of complement factors in 21 patients with NMOSD and 25 patients with GBS. Ba, an activation marker of the alternative complement pathway, was elevated in the acute phases of both NMOSD and GBS. Meanwhile, sC5b-9, an activation marker generated by the terminal complement pathway, was elevated in NMOSD but not in GBS. Complement factor H (CFH), a complement regulatory factor, was decreased in the acute phase as well as in the remission phase of NMOSD, but not in any phases of GBS. Together, these findings suggest that complement biomarkers, such as Ba, sC5b-9 and CFH in peripheral blood, have potential utility in understanding the pathological status of NMOSD.