The crosstalk between SUMOylation and immune system in host-pathogen interactions.

Pathogens can not only cause infectious diseases, immune system diseases, and chronic diseases, but also serve as potential triggers or initiators for certain tumors. They directly or indirectly damage human health and are one of the leading causes of global deaths. Small ubiquitin-like modifier (SUMO) modification, a type of protein post-translational modification (PTM) that occurs when SUMO groups bond covalently to particular lysine residues on substrate proteins, plays a crucial role in both innate and adaptive immunologic responses, as well as pathogen-host immune system crosstalk. SUMOylation participates in the host's defense against pathogens by regulating immune responses, while numerically vast and taxonomically diverse pathogens have evolved to exploit the cellular SUMO modification system to break through innate defenses. Here, we describe the characteristics and multiple functions of SUMOylation as a pivotal PTM mechanism, the tactics employed by various pathogens to counteract the immune system through targeting host SUMOylation, and the character of the SUMOylation system in the fight between pathogens and the host immune system. We have also included a summary of the potential anti-pathogen SUMO enzyme inhibitors. This review serves as a reference for basic research and clinical practice in the diagnosis, prognosis, and treatment of pathogenic microorganism-caused disorders.

Subspace Identification of Bridge Frequencies Based on the Dimensionless Response of a Two-Axle Vehicle.

As an essential reference to bridge dynamic characteristics, the identification of bridge frequencies has far-reaching consequences for the health monitoring and damage evaluation of bridges. This study proposes a uniform scheme to identify bridge frequencies with two different subspace-based methodologies, i.e., an improved Short-Time Stochastic Subspace Identification (ST-SSI) method and an improved Multivariable Output Error State Space (MOESP) method, by simply adjusting the signal inputs. One of the key features of the proposed scheme is the dimensionless description of the vehicle-bridge interaction system and the employment of the dimensionless response of a two-axle vehicle as the state input, which enhances the robustness of the vehicle properties and speed. Additionally, it establishes the equation of the vehicle biaxial response difference considering the time shift between the front and the rear wheels, theoretically eliminating the road roughness information in the state equation and output signal effectively. The numerical examples discuss the effects of vehicle speeds, road roughness conditions, and ongoing traffic on the bridge identification. According to the dimensionless speed parameter Sv1 of the vehicle, the ST-SSI (Sv1 < 0.1) or MOESP (Sv1 ≥ 0.1) algorithm is applied to extract the frequencies of a simply supported bridge from the dimensionless response of a two-axle vehicle on a single passage. In addition, the proposed methodology is applied to two types of long-span complex bridges. The results show that the proposed approaches exhibit good performance in identifying multi-order frequencies of the bridges, even considering high vehicle speeds, high levels of road surface roughness, and random traffic flows.

The kinesin Kif21b binds myosin Va and mediates changes in actin dynamics underlying homeostatic synaptic downscaling.

Homeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Postsynaptic guanylate kinase-associated protein (GKAP) controls the bidirectional synaptic scaling of AMPA receptors (AMPARs); however, mechanisms by which chronic activity triggers cytoskeletal remodeling to downscale synaptic transmission are barely understood. Here, we report that the microtubule-dependent kinesin motor Kif21b binds GKAP and likewise is located in dendritic spines in a myosin Va- and neuronal-activity-dependent manner. Kif21b depletion unexpectedly alters actin dynamics in spines, and adaptation of actin turnover following chronic activity is lost in Kif21b-knockout neurons. Consistent with a role of the kinesin in regulating actin dynamics, Kif21b overexpression promotes actin polymerization. Moreover, Kif21b controls GKAP removal from spines and the decrease of GluA2-containing AMPARs from the neuronal surface, thereby inducing homeostatic synaptic downscaling. Our data highlight a critical role of Kif21b at the synaptic actin cytoskeleton underlying homeostatic scaling of neuronal firing.

Understanding the molecular mechanism of leaf morphogenesis in vegetable crops conduces to breeding process.

Leaf morphology can affect the development and yield of plants by regulating plant architecture and photosynthesis. Several factors can determine the final leaf morphology, including the leaf complexity, size, shape, and margin type, which suggests that leaf morphogenesis is a complex regulation network. The formation of diverse leaf morphology is precisely controlled by gene regulation on translation and transcription levels. To further reveal this, more and more genome data has been published for different kinds of vegetable crops and advanced genotyping approaches have also been applied to identify the causal genes for the target traits. Therefore, the studies on the molecular regulation of leaf morphogenesis in vegetable crops have also been largely improved. This review will summarize the progress on identified genes or regulatory mechanisms of leaf morphogenesis and development in vegetable crops. These identified markers can be applied for further molecular-assisted selection (MAS) in vegetable crops. Overall, the review will contribute to understanding the leaf morphology of different crops from the perspective of molecular regulation and shortening the breeding cycle for vegetable crops.

Endoscopic Evaluation at 1 Month After Ileocolic Resection for Crohn's Disease Predicts Future Postoperative Recurrence and Is Safe.

BACKGROUND: Endoscopy remains the gold standard for evaluating postoperative recurrence in Crohn's disease. Timely therapy adjustment according to endoscopic findings can improve long-term outcomes. OBJECTIVE: We aimed to determine the characteristics, clinical values, and safety of the endoscopic evaluation at 1 month after surgery. DESIGN: This was a prospective observational study. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: Patients with Crohn's disease undergoing ileocolic resection between January 2016 and November 2018 were included. INTERVENTIONS: The first postoperative ileocolonoscopy was performed at 4-5 weeks after surgery. MAIN OUTCOME MEASURES: The primary outcome was postoperative recurrence within 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors. RESULTS: Among 84 ileocolonoscopies at 4-5 weeks, no endoscopic complication occurred. The main endoscopic findings at the first evaluation were anastomotic circumferential ulcers (10, 11.9%), anastomotic scattered ulcers (35, 41.7%), ulcers in the neoterminal ileum (16, 19.0%), edema in anastomosis (50, 59.5%), mild narrowing in anastomosis (7, 8.3%), and mild narrowing in neoterminal ileum (3, 3.6%). Anastomotic scattered ulcers were associated with future postoperative recurrence (OR, 2.532 (95% CI, 1.02-6.32), p = 0.046). Fecal calprotectin >150 ug/g on postoperative day 14 could predict anastomotic scattered ulcers (OR' 2.91 (95% CI, 1.31-7.47), p = 0.027). The modified Rutgeerts score was used to define endoscopic findings: i0, 37 (44.0%); i1, 4 (4.8%); i2a, 29 (34.5%); i2b, 11 (13.1%); i3, 0; i4, 3 (3.6%). Score ≥i2a were associated with future postoperative recurrence (OR, 3.17 (95% CI, 1.22-8.27), p = 0.018). No factor was associated with a Rutgeerts score of ≥i2a at the first endoscopic evaluation. LIMITATIONS: This was a single-center study with a small cohort of patients. CONCLUSIONS: Endoscopic evaluation at 1 month after surgery in CD was safe. Anastomotic scattered ulcers occurred in nearly half of patients and were associated with future postoperative recurrence. See Video Abstract at http://links.lww.com/DCR/B760.LA EVALUACIÓN ENDOSCÓPICA A UN MES DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PARA LA ENFERMEDAD DE CROHN, PREDICE FUTURA RECURRENCIA POSOPERATORIA Y ES SEGURAANTECEDENTES:La endoscopia sigue siendo el estándar de oro para evaluar la recurrencia posoperatoria en la enfermedad de Crohn (EC). El ajuste oportuno en la terapia de acuerdo con los hallazgos endoscópicos, puede mejorar los resultados a largo plazo.OBJETIVO:Determinar las características, valores clínicos y seguridad de la evaluación endoscópica, al mes de la cirugía.DISEÑO:Estudio observacional prospectivo.ENTORNO CLINICO:El estudio se llevó a cabo en un hospital de referencia terciario.PACIENTES:Se incluyeron pacientes con EC sometidos a resección ileocólica entre enero de 2016 y noviembre de 2018.INTERVENCIONES:La primera ileocolonoscopia posoperatoria se realizó a las 4-5 semanas posteriores a la cirugía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia posoperatoria dentro de los 12 meses posteriores a la cirugía. Se realizaron análisis univariados y multivariados para identificar factores de riesgo.RESULTADOS:Entre 84 ileocolonoscopias a las 4-5 semanas, no ocurrió ninguna complicación endoscópica. Los principales hallazgos endoscópicos en la primera evaluación, fueron úlceras anastomóticas circunferenciales (10, 11,9%), úlceras anastomóticas dispersas (35, 41,7%), úlceras en el íleon neo-terminal (16, 19,0%), edema en la anastomosis (50, 59,5%), estrechamiento leve en la anastomosis (7, 8,3%) y estrechamiento leve en el íleon neo-terminal (3, 3,6%). Las úlceras anastomóticas dispersas se asociaron con recurrencia posoperatoria futura (OR, 2,532 (95% CI, 1,02-6,32), p = 0,046). La calprotectina fecal en el post d 14 > 150 ug / g podría predecir úlceras anastomóticas dispersas (OR' 2,91 (95% CI, 1,31-7,47), p = 0,027). Se utilizó la puntuación de Rutgeerts modificada para definir los hallazgos endoscópicos: i0, 37 (44,0%); i1, 4 (4,8%); i2a, 29 (34,5%); i2b, 11 (13,1%); i3, 0; i4, 3 (3,6%). La puntuación ≥i2a se asoció con recurrencia posoperatoria futura (OR, 3,17 (95% CI, 1,22-8,27), p = 0,018). Ningún factor se asoció con ≥i2a en la primera endoscopia.LIMITACIONES:Estudio de un solo centro con una pequeña cohorte de pacientes.CONCLUSIONES:La evaluación endoscópica al mes de la cirugía en EC, fue segura. Se produjeron úlceras anastomóticas dispersas en casi la mitad de los pacientes y se asociaron con una futura recurrencia posoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B760. (Traducción - Dr. Fidel Ruiz Healy).

Role of Extended Mesenteric Excision in Postoperative Recurrence of Crohn's Colitis: A Single-Center Study.

INTRODUCTION: The mesentery is involved in Crohn's disease. The impact of the extent of mesenteric resection on postoperative disease progression in Crohn's disease remains unconfirmed. This study aimed to determine the association between resection of the mesentery and postoperative outcomes in patients with Crohn's colitis (CC) undergoing colorectal surgery. METHODS: Patients with CC who underwent colorectal resection between January 2000 and December 2018 were reviewed, and the data were gathered from a prospectively maintained database. Patients were divided into 2 groups according to the extent of mesenteric resection, the extensive mesenteric excision (EME) group and the limited mesenteric excision (LME) group. Outcomes including early postoperative morbidities and surgical recurrence were compared between the 2 groups. RESULTS: Of the 126 patients included, 60 were in the LME group and 66 in the EME group. There was no significant difference between the 2 groups in early postsurgical outcomes except the intraoperative blood loss was increased in the LME group (P = 0.002). Patients in the EME group had a longer postoperative surgical recurrence-free survival time when compared with those in the LME group (P = 0.01). LME was an independent predictor of postoperative surgical recurrence (hazard ratio 2.67, 95% confidence interval 1.04-6.85, P = 0.04). This was further confirmed in the subgroup analysis of patients undergoing colorectal resection and anastomosis (hazard ratio 2.83, 95% confidence interval 1.01-7.96, P = 0.048). DISCUSSION: In patients undergoing surgery for CC, inclusion of the mesentery is associated with similar short-term outcomes and improved long-term outcomes compared with those seen when the mesentery is retained.

A biomimicking design for mechanical knee joints.

In this paper we present a new bioinspired bicondylar knee joint that requires a smaller actuator size when compared to a constant moment arm joint. Unlike existing prosthetic joints, the proposed mechanism replicates the elastic, rolling and sliding elements of the human knee. As a result, the moment arm that the actuators can impart on the joint changes as function of the angle, producing the equivalent of a variable transmission. By employing a similar moment arm-angle profile as the human knee the peak actuator force for stair ascent can be reduced by 12% compared to a constant moment arm joint addressing critical impediments in weight and power for robotics limbs. Additionally, the knee employs mechanical 'ligaments' containing stretch sensors to replicate the neurosensory and compliant elements of the joint. We demonstrate experimentally how the ligament stretch can be used to estimate joint angle, therefore overcoming the difficulty of sensing position in a bicondylar joint.