The nematode effector Mj-NEROSs interacts with Rieske's iron-sulfur protein influencing plastid ROS production to suppress plant immunity.

Root-knot nematodes (RKN; Meloidogyne species) are plant pathogens that introduce several effectors in their hosts to facilitate infection. The actual targets and functioning mechanism of these effectors largely remain unexplored. This study illuminates the role and interplay of the Meloidogyne javanica nematode effector ROS suppressor (Mj-NEROSs) within the host plant environment. Mj-NEROSs suppresses INF1-induced cell death as well as flg22-induced callose deposition and reactive oxygen species (ROS) production. A transcriptome analysis highlighted the downregulation of ROS-related genes upon Mj-NEROSs expression. NEROSs interacts with the plant Rieske's iron-sulfur protein (ISP) as shown by yeast-two-hybrid and bimolecular fluorescence complementation. Secreted from the subventral pharyngeal glands into giant cells, Mj-NEROSs localizes in the plastids where it interacts with ISP, subsequently altering electron transport rates and ROS production. Moreover, our results demonstrate that isp Arabidopsis thaliana mutants exhibit increased susceptibility to M. javanica, indicating ISP importance for plant immunity. The interaction of a nematode effector with a plastid protein highlights the possible role of root plastids in plant defense, prompting many questions on the details of this process.

Oocyte mitochondria link maternal environment to offspring phenotype.

During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies1, frogs1, and humans2. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance1,2, is regulated by maternal insulin signaling1. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)2. In Caenorhabditis elegans, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes3. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring's ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp-1 (complex III subunit) altered offspring's response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild-type isp-1 in germ cells (oocytes) was sufficient to restore offspring's normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring's response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother's environment to adaptive changes in offspring metabolism. The data also raise the possibility that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria is to tailor offspring metabolism to best match the environment of their mother.

Prevalence and Clinical Characteristics of Sleeping Paralysis: A Systematic Review and Meta-Analysis.

Sleep paralysis (SP) is a mixed state of consciousness and sleep, combining features of rapid eye movement (REM) sleep with those of wakefulness. The exact cause of SP is unknown, and its prevalence varies among the studies. We aim to identify SP's global prevalence, the affected population's characteristics, and the SP's clinical picture. We searched three databases (PubMed, Scopus, and Web of Science (WoS)) using a unique search strategy to identify eligible studies. All observational studies identifying the prevalence or frequency of sleeping paralysis were included. No exclusions are made based on country, race, or questionnaire. The analysis was performed using the latest version of R software (R Core Team, Vienna, Austria). The analysis included 76 studies from 25 countries with 167,133 participants. The global prevalence of SP was 30% (95% CI (22%, 39%)). There were similar frequencies of isolated SP and SP (33%, 95% CI (26%, 42%), I2 = 97%, P <0.01; 31%, 95% CI (21%, 43%), I2 = 100%, P = 0, respectively). A subgroup analysis showed that the majority of those who experienced SP were psychiatric patients (35%, 95% CI (20%, 55%), I2 = 96%, P <0.01). The prevalence among non-psychiatric patients was among students (34%, 95% CI (23%, 47%), I2 = 100%, P = 0). Auditory and visual hallucinations were reported in 24.25% of patients. Around 4% had only visual hallucinations. Meta-regression showed no association between the frequency of SP and sex. Publication bias was detected among the included studies through visual inspection of funnel plot asymmetry. Our findings revealed that 30% of the population suffered from SP, especially psychiatric patients and students. The majority of SP cases lacked associated hallucinations, while a noteworthy proportion experienced combined visual and auditory hallucinations.

Effects of temperature and initial pH on the growth of four dominant cyanobacteria species in biological soil crusts.

Biological soil crusts are of great significance for environment health and sustainable development in arid and semi-arid areas. Cyanobacteria, Microcoleus vaginatus, Scytonema sp., Nostoc sp., and Anabaena sp. are the dominant species in microbial community of biological soil crusts worldwide. Considering their broad application prospect, it is meaningful to cultivate them extensively. We examined the effects of temperature (10, 20, 25, 30, 35 ℃) and initial pH (4, 6, 8, 10, 12) on biomass and solution pH towards the four species of cyanobacteria with liquid culture in laboratory. The results showed that the biomass of the four cyanobacterial species grew slowly under 20 ℃, and that all species could grow in 25-35 ℃, with the highest growth rate at 25 and 30 ℃. The optimum culture temperature of different cyanobacterial species was slightly different. The optimum culture temperature was 25-30 ℃ for Scytonema sp. and Nostoc sp., and 30 ℃ for M. vaginatus and Anabaena sp. The four cyanobacterial species had a strong ability to adjust solution pH and proliferate in five different initial pH conditions. The highest maximum biomass and specific growth rate were recorded in the culture environment with initial pH of 4, while the lowest maximum biomass and specific growth rate were observed in initial pH of 12. Our results would provide scientific basis for the propagation of dominant cyanobacteria in biological soil crusts.

Dual Action of Reduced Allergenicity and Improved Memory of Instant Soybean Powder Hydrolysates.

Soy allergens are susceptible to inducing allergic reactions in infants and young animals, which have an impact on the effective daily utilization of proteins. In this study, we used Alcalase-hydrolyzed instant soybean powder (ISP) to clarify the sensitization changes of instant soybean powder hydrolysates (ISPH), and we explored the assisted memory-enhancing effects. BALB/c mice in the ISPH group showed significant improvement in the allergy symptoms, with their allergy symptom scores decreasing to (1.57 ± 0.53) and their specific serum IgE and IgG1 binding capacity decreasing by 28.00 and 25.73% (P < 0.05), which suppressed the mast cell degranulation rate. Meanwhile, the plasma HIS and IL-4 levels decreased by 12.59 and 25.32%, and the plasma INF-γ and IL- 10 levels increased by 30.64 and 27.79%, which obviously regulated the imbalance of Th1/Th2 cells and attenuated the tissue damage (P < 0.05). Furthermore, ISPH improved behavioral characteristics, increased cholinergic system activity, reduced neuronal cell damage or apoptosis, and increased the number of Nissl bodies to help improve memory in Kunming mice (P < 0.05). In general, alcalase-hydrolyzed ISP had the dual effects of reducing allergenicity and aiding in memory improvement.

Human papillomavirus expression in relation to biological behavior, Ki-67 proliferative marker, and P53 prognostic marker in Schneiderian papilloma.

Various malignant and benign tumors can arise in the sinonasal cavity, including inverted papilloma (IP), a benign neoplasm with unique clinical characteristics. However, the mechanisms involved in the recurrence, occurrence, and malignant transformation of IP remain debatable. This study aimed to investigate the impact of human papillomavirus (HPV) infections on IP by comparing the number of infections in cases with epithelial tissue dysplasia and explore the predictive role of proliferative and prognostic markers in dysplasia. Tissue blocks from 35 cases of sinonasal papilloma, collected between 2015 and 2021 from the laboratory archives of the Medical City of Ghazi Al-Hererri Hospital in Baghdad, Iraq, were immunohistochemically stained with monoclonal antibodies (mAbs) to detect Ki-67 and p53. A quantitative immunohistochemical analysis was conducted to analyze the results. Polymerase chain reaction (PCR) was performed to detect HPV genotypes 16/18 and 6/11 in the tissues. There was an insignificant increase in Ki-67 and p53 expression in inverted papillomas with dysplasia. HPV11 was the most prevalent genotype in 34.3% of the patients, followed by HPV16 and HPV18 in 31.4% of the patients for each virus. The least common virus detected was human papillomavirus 6 (8.6%), which did not show any significant association with the degree of dysplasia. Viral detection proliferation and apoptosis had no impact on tumor dysplasia amongst all the patients, showing no relationship with the evaluated cases.

Effect of Imperial Smelting Process Slag Addition in Self Compacting Concrete Concrete on the Efficiency of Electrochemical Chloride Extraction.

This paper presents the analysis of how ISP slag addition affects the effectiveness of chloride extraction from self-compacting concrete. Corrosion processes were initiated by chloride ions added to concrete by the method accelerated with an electric field. Corrosion of reinforcement was monitored using the method of linear polarization resistance (LPR). Polarization measurements of steel reinforcement and chloride profiles were analysed to evaluate the effectiveness of electrochemical extraction. Microstructural analysis was conducted on a specimen of concrete after migration and extraction of chlorides. The presence of chloride ions and the application of an electric field during migration were tested with respect to the changed microstructure of concrete evaluated on the basis of image analysis using a scanning electron microscope (SEM). The research contributes to a better understanding of the corrosion processes caused by the presence of chloride ions in concretes in which ISP slag was used as a substitute for sand in various amounts. Thanks to the treatments of concrete with already corroding reinforcement bars, it can be concluded that the moderate replacement of sand with ISP slag limited to 25% allows for the effective inhibition of corrosion processes taking place in these concretes. However, it is not possible to completely withdraw already started corrosion processes in steel. The observations of the microstructure of concrete in which sand was completely replaced with ISP slag indicate that after prolonged use of the chloride extraction process, we can expect a change in the microstructure and the formation of ettringite, which may cause the concrete structure to burst. The obtained information will contribute to the development of modelling methods for chloride ion extraction from a wide range of currently used concretes.

Changing Treatment Philosophy of Slipped Capital Femoral Epiphysis (SCFE) after Introduction of the Modified Dunn Procedure (MDP): Our Experience with MDP and Its Complications.

BACKGROUND: The modified Dunn procedure (MDP) has become popular during the last 16 years to treat severely displaced slipped capital femoral epiphysis (SCFE) while "in situ" pinning (ISP) has remained valid to treat mild to moderate SCFE, although the indication limit of the Southwick angle (SA) has not yet been established for either procedure. In this context, we reviewed two cohorts of patients with SCFE, one treated by ISP and the other by MDP. We also tried to better elucidate the etiopathogenesis of hip instability, a severe complication of MDP. METHODS: Fifty-one consecutive patients with 62 hips affected by SCFE were treated by us from 2015 to 2019: 48 hips with a SA ≤ 40° had ISP while 14, with the SA > 40°, had MDP. The latter also had a CT scan to better investigate the SCFE morphology. Results were assessed using the Harris Hip Score. RESULTS: The mean length of follow up of the two cohorts was 5.4 years (range: 3 to 8 years). Of the 35 hips operated by ISP with a full follow-up evaluation, 30 had an excellent or good result, 3, fair, and 2, poor. Of the 14 hips that underwent MDP, 11 had an excellent or good result, 1, fair, and 2, poor. A CT scan showed femoro-acetabular incongruency in two unstable hips following MDP. CONCLUSIONS: We performed ISP in chronic SCFE with the SA ≤ 40° and MDP in acute and chronic SCFE with the SA > 40°, with satisfactory results. In both acute-on-chronic and chronic long-lasting SCFE with severe displacement, planned for MDP, a CT scan should be carried out to evaluate possible femoro-acetabular incongruency that may cause hip instability.

Polyplacophoran Feeding Traces on Mediterranean Pliocene Sirenian Bones: Insights on the Role of Grazing Bioeroders in Shallow-Marine Vertebrate Falls.

Chitons (Polyplacophora) include some of the most conspicuous bioeroders of the present-day shallow seas. Abundant palaeontological evidence for the feeding activity of ancient chitons is preserved in the form of radular traces that are usually found on invertebrate shells and hardgrounds. We report on widespread grazing traces occurring on partial skeletons of the extinct sirenian Metaxytherium subapenninum from the Lower Pliocene (Zanclean) of Arcille (Grosseto Province, Tuscany, Italy). These distinctive ichnofossils are described under the ichnotaxonomic name Osteocallis leonardii isp. nov. and interpreted as reflecting substrate scraping by polyplacophorans. A scrutiny of palaeontological literature reveals that similar traces occur on fossil vertebrates as old as the Upper Cretaceous, suggesting that bone has served as a substrate for chiton feeding for more than 66 million years. Whether these bone modifications reflect algal grazing, carrion scavenging or bone consumption remains unsure, but the first hypothesis appears to be the most parsimonious, as well as the most likely in light of the available actualistic data. As the role of bioerosion in controlling fossilization can hardly be overestimated, further research investigating how grazing organisms contribute to the biostratinomic processes affecting bone promises to disclose new information on how some marine vertebrates manage to become fossils.

Specialized herbivory in fossil leaves reveals convergent origins of nyctinasty.

Plants can move in various complex ways in response to external stimuli.1,2 These mechanisms include responses to environmental triggers, such as tropic responses to light or gravity and nastic responses to humidity or contact.3 Nyctinasty, the movements involving circadian rhythmic folding at night and opening at daytime of plant leaves or leaflets, has attracted the attention of scientists and the public for centuries.4,5 In his canonical work entitled The Power of Movement in Plants, Charles Darwin carried out pioneering observations to document the diverse range of movements in plants.6 His systematic examination of plants showing "sleep [folding] movements of leaves" led him to conclude that the legume family (Fabaceae) includes many more nyctinastic species than all other families combined.3 Darwin also found that a specialized motor organ, the pulvinus, is responsible for most sleep movements of plant leaves, although differential cell division and the hydrolysis of glycosides and phyllanthurinolactone also facilitate nyctinasty in some plants.7,8 However, the origin, evolutionary history, and functional benefits of foliar sleep movements remain ambiguous owing to the lack of fossil evidence for this process. Here, we document the first fossil evidence of foliar nyctinasty based on a symmetrical style of insect feeding damage (Folifenestra symmetrica isp. nov.) in gigantopterid seed-plant leaves from the upper Permian (∼259-252 Ma) of China. The pattern of insect damage indicates that the host leaves were attacked when mature but folded. Our finding reveals that foliar nyctinasty extends back to the late Paleozoic and evolved independently among various plant lineages.

Prospective 5-year follow-up of L5-S1 versus L4-5 midline decompression and interspinous-interlaminar fixation as a stand-alone treatment for spinal stenosis compared with laminectomies.

Background: Spinal stenosis treatment includes laminectomies with or without fusion or with interspinous distraction with or without fixation. Lack of published data on interspinous fixation devices (IFD) at L5-S1 is less considered as an option due to the smaller anatomical S1 spinous process and the higher stresses from the immobile sacrum. Our objective was to evaluate the outcomes of an IFD used as a stand-alone treatment for spinal stenosis at L5-S1 and L4-5 compared to historical data on open laminectomies. Methods: Prospective comparative cohort study (Level 2) looking at collected preoperatively and postoperatively Visual Analog Scores (VAS) and Oswestry Disability Index (ODI) data, complications, and revision rates on 100 consecutive patients with spinal stenosis treated with midline decompression and InSpan (InSpan LLC, Malden, MA, USA) IFD, at L5-S1 and L4-5, up to five-year follow-up. All patients were treated by a single surgeon in an academic private practice. Historical published outcome data for open laminectomies were compared. Results: Among the 100 patients, 45 underwent surgery at L5-S1 with a mean VAS pain score that decreased by 75% and ODI improved by 63% (P<0.001). Fifty-five patients had surgery at L4-5 with mean VAS and ODI scores improved by 80% and 66% (P<0.001) respectively. Preoperative and postoperative ODI and preoperative VAS scores were similar at L5-S1 and L4-5, however, postoperative VAS scores were significantly less for L4-5 versus L5-S1 (P<0.01). All surgeries were completed in less than one hour. There was a total of one L4-5 revision (1.8%) and two L5-S1 revisions (4.4%). Comparable laminectomy data showed decrease in VAS and ODI scores by 51% and 62% (P<0.05). The reoperation rate for laminectomies at five to ten years varied up to 24%. Conclusions: Spinal stenosis patients treated with midline decompression and InSpan IFD, used as a stand-alone treatment for interspinous-interlaminar fixation, at L4-5 and L5-S1, showed improved outcome scores and low complication and revision rates at five years and were comparable to historical open laminectomy data. InSpan is a successful substitute for laminectomies in selected patients and was performed in less than 60 minutes. We recommend choosing the appropriately sized implant to achieve adequate distraction decompression to avoid recurrent symptoms.

Uniformity Correction of CMOS Image Sensor Modules for Machine Vision Cameras.

Flat-field correction (FFC) is commonly used in image signal processing (ISP) to improve the uniformity of image sensor pixels. Image sensor nonuniformity and lens system characteristics have been known to be temperature-dependent. Some machine vision applications, such as visual odometry and single-pixel airborne object tracking, are extremely sensitive to pixel-to-pixel sensitivity variations. Numerous cameras, especially in the fields of infrared imaging and staring cameras, use multiple calibration images to correct for nonuniformities. This paper characterizes the temperature and analog gain dependence of the dark signal nonuniformity (DSNU) and photoresponse nonuniformity (PRNU) of two contemporary global shutter CMOS image sensors for machine vision applications. An optimized hardware architecture is proposed to compensate for nonuniformities, with optional parametric lens shading correction (LSC). Three different performance configurations are outlined for different application areas, costs, and power requirements. For most commercial applications, the correction of LSC suffices. For both DSNU and PRNU, compensation with one or multiple calibration images, captured at different gain and temperature settings are considered. For more demanding applications, the effectiveness, external memory bandwidth, power consumption, implementation, and calibration complexity, as well as the camera manufacturability of different nonuniformity correction approaches were compared.

Comparison of bronchial methylene blue staining and modified inflation-deflation method in identifying the intersegmental plane during lung segmentectomy.

Background: Identification of the intersegmental plane (ISP) is the critical step in lung segmentectomy because of the complicated anatomic variations. Bronchial methylene blue staining was developed by our team in 2015 and is now commonly used at our center, it could rapidly and accurately identify the ISP. In this study, we aimed to compare bronchial methylene blue staining with the modified inflation-deflation method in terms of their perioperative characteristics and to present our experience of the methylene blue method. Methods: From June 2020 to September 2021, the data of 112 patients with pulmonary ground-glass nodules who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Sixty-two patients underwent bronchial methylene blue staining, and 50 patients underwent the modified inflation-deflation method. Results: Both methods could accurately identify the ISP. The time taken to clearly display the ISP (82.94±28.08 vs. 868.20±145.89 seconds; P<0.001) and the surgical duration (131.69±32.05 vs. 146.08±28.11 minutes; P=0.014) were significantly shorter in the bronchial methylene blue staining group than in the modified inflation-deflation group. There were no significant differences between the two groups in the bleeding volume, drainage time, and length of postoperative hospital stay, as well as in most other perioperative characteristics. Conclusions: Compared with the modified inflation-deflation method, the bronchial methylene blue staining method can quickly display the ISP and shorten the surgical duration. This method is safe and feasible, can be widely applied during thoracoscopic anatomic segmentectomy.

Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.

Myocardial infarction (MI) triggers an inflammatory response that transitions from pro-inflammatory to reparative over time. Restoring sympathetic nerves in the heart after MI prevents arrhythmias. This study investigated if reinnervation altered the immune response after MI. This study used quantitative multiplex immunohistochemistry to identify the immune cells present in the heart 2 weeks after ischemia-reperfusion. Two therapeutics stimulated reinnervation, preventing arrhythmias and shifting the immune response from inflammatory to reparative, with fewer pro-inflammatory macrophages and more regulatory T cells and reparative macrophages. Treatments did not alter macrophage phenotype in vitro, which suggested reinnervation contributed to the altered immune response.

Effect of antifreeze proteins on the freeze-thaw cycle of foods: fundamentals, mechanisms of action, current challenges and recommendations for future work.

Freezing is widely used in food preservation, but if not carried out properly, ice crystals can multiply (nucleation) or grow (recrystallization) rapidly. This also affects thawing, causing structural damage and affecting overall quality. The objective of this review is to comprehensively study the cryoprotective effect of antifreeze proteins (AFPs), highlighting their role in the freeze-thaw process of food. The properties of AFPs are based on their thermal hysteresis capacity (THC), on the modification of crystal morphology and on the inhibition of ice recrystallization. The mechanism of action of AFPs is based on the adsorption-inhibition theory, but the specific role of hydrogen and hydrophobic bonds/residues and structural characteristics is also detailed. Because of the properties of AFPs, they have been successfully used to preserve the quality of a wide variety of refrigerated and frozen foods. Among the limitations of the use of AFPs, the high cost of production stands out, but currently there are solutions such as the use the production of recombinant proteins, cloning and chemical synthesis. Although in vitro, in vivo and human studies have shown that AFPs are non-toxic, their safety remains a matter of debate. Further studies are recommended to expand knowledge about AFPs, to reduce costs in their large-scale production, to understand their interaction with other food compounds and their possible effects on the consumer.

Strategic job market-guided development of pharmacy bachelor's curriculum and its importance in maintaining the profession viability in the Middle Eastern countries: Colleges of pharmacy in the UAE as a model.

The Middle East has high youth population; however, it is challenged by uncertain economic situation. Higher education plays a crucial role in the development of nations by equipping generations with the knowledge and skill through cumulative curriculum development. Like other professions, pharmacy is a dynamic field of study where continuous improvements are required to keep the viability of the profession and endow future generations with up to date skills. This article describes a strategy for pharmacy curriculum development considering four layers. The strategy starts from the understanding of the current situation in a university, looking into national, international accreditations and job market. The strategy covers development from program to subject's level. The strategy is applied to pharmacy programs in the UAE. Upon analysis, several recommendations were obtained for curriculum improvements. At individual university level, there is a need to work on clinical oriented topics in the curriculum to fit with international accreditation and country's vision. Details on this can be taken form deeper analysis of job market and stakeholders in the UAE. On the national level, unifications of total credit hours for the degree across universities needs to be envisaged with limits on contact experiential hours. The strategy has the potential of extrapolating to other Middle Eastern countries.

General Internet service assessment by latency including partial measurements.

Latency is one of the key parameters of Internet services. However, it is difficult to correctly assess a service by its latency. Many latency measurements are blocked en route by routers and firewalls. For this reason, the service latency is not fully known. This work proposes a method to assess Internet services including the blocked latency measurements. Survival theory is applied to process latency values. The results show that the omission of blocked latencies from statistical processing severely underestimates the service latency. Two Internet service providers were compared as an example. Their latency difference was 9 ms using the traditional approach. The survival latency resulted in a difference of 17 ms. The method of survival latency can be used to increase revenues in e-commerce and to improve the experience of online gaming.

Modulation of the proteoglycan receptor PTPσ promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality rates. However, extant investigations have mainly focused on gray matter injury within the primary injury site after ICH rather than on white matter (WM) injury in the brain and spinal cord. This focus partly accounts for the diminished therapeutic discovery. Recent evidence suggests that chondroitin sulphate proteoglycans (CSPG), which can bind to the neural transmembrane protein tyrosine phosphatase-sigma (PTPσ), may facilitate axonal regrowth and remyelination by ameliorating neuroinflammation. METHODS: A clinically relevant ICH model was established using adult C57BL/6 mice. The mice were then treated systemically with intracellular sigma peptide (ISP), which specifically targets PTPσ. Sensorimotor function was assessed by various behavioral tests and electrophysiological assessment. Western blot was used to verify the expression levels of Iba-1 and different inflammatory cytokines. The morphology of white matter tracts of brain and spinal cord was evaluated by immunofluorescence staining and transmission electron microscopy (TEM). Adeno-associated virus (AAV) 2/9 injection was used to assess the ipsilateral axonal compensation after injury. Parallel in vitro studies on the effects of CSPG interference on oligodendrocyte-DRG neuron co-culture explored the molecular mechanism through which ISP treatment promoted myelination capability. RESULTS: ISP, by targeting PTPσ, improved WM integrity and sensorimotor recovery via immunomodulation. In addition, ISP administration significantly decreased WM injury in the peri-hematomal region as well as cervical spinal cord, enhanced axonal myelination and facilitated neurological restoration, including electrophysiologically assessed sensorimotor functions. Parallel in vitro studies showed that inhibition of PTPσ by ISP fosters myelination by modulating the Erk/CREB signaling pathway. CONCLUSIONS: Our findings revealed for the first time that manipulation of PTPσ signaling by ISP can promote prolonged neurological recovery by restoration of the integrity of neural circuits in the CNS through modulation of Erk/CREB signaling pathway.

Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway.

Novel drugs are required for non-small cell lung cancer (NSCLC) treatment urgently. Repurposing old drugs as new treatments is a practicable approach with time and cost savings. Some studies have shown that carrimycin, a Chinese Food and Drug Administration (CFDA)-approved macrolide antibiotic, possesses potent anti-tumor effects against oral squamous cell carcinoma. However, its detailed component and underlying mechanisms in anti-NSCLC remain unknown. In our study, isovalerylspiramycin I (ISP-I) was isolated from carrimycin and demonstrated a remarkable anti-NSCLC efficacy in vitro and in vivo with a favorable safety profile. It has been proven that in NSCLC cell lines H460 and A549, ISP-I could induce G2/M arrest and apoptosis, which was mainly attributed to ROS accumulation and subsequently PI3K/AKT signaling pathway inhibition. Numerous downstream genes including mTOR and FOXOs were also changed correspondingly. An observation of NAC-induced reverse effect on ISP-I-leading cell death and PI3K/AKT pathway inhibition, emphasized the necessity of ROS signaling in this event. Moreover, we identified ROS accumulation and PI3K/AKT pathway inhibition in tumor xenograft models in vivo as well. Taken together, our study firstly reveals that ISP-I is a novel ROS inducer and may act as a promising candidate with multi-target and low biological toxicity for anti-NSCLC treatment.

Assessment of PCL between dental implant prosthesis and natural teeth using a digital force analyzer.

BACKGROUND: The prime concern of an implant-supported prosthesis (ISP) is to maintain an optimal proximal contact tightness, which further maintains arch integrity, improves masticatory effectiveness, and minimizes peri-implantitis. OBJECTIVE: To investigate the loss of proximal contact tightness between single tooth implant-supported prosthesis and the adjacent natural teeth. METHODS: Forty patients treated by a single mandibular first molar ISP, aged between 18-50 years were selected. All were randomly allocated in Group I and Group II. Group I, 20 subjects who have received ISP without an insertion of Essix retainer, and Group II patients received an insertion with Essix retainer. The groups were subdivided into Subgroup A, B, and Subgroup C, D, in which A and C are control groups. To measure the tightness at proximal contact points, a digital force analyzer was used. Proximal contact tightness (PCT) was measured immediately after the placement of the prosthesis, 3 months, 6 months, and 1-year follow-up respectively, and the PCT values at end of 1 year were statistically evaluated. Statistical analysis was done, mean and standard deviation was calculated by independent sample t-test wit p< 0.05 as a statistically significant value. RESULTS: In Group I, towards the end of 1 year, 2.09 N (65.5%) and 1.50 N (53.1%) loss of PCT were found on mesial and distal contact areas respectively. In Group II, loss of PCT at mesial contact area was 0.87 N (28.9%) and at distal contact area was 1.77 N (53.3%), which is significantly less compared with the non-usage of Essix retainer (p< 0.05). CONCLUSION: The usage of Essix retainer, PCT increases especially on the mesial contact area. The frequency of contact loss was decreased. Thus, to minimize the loss of proximal contact the usage of Essix retainer is recommended.