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Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoAmediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endodermC&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis. [ABSTRACT FROM AUTHOR]

Objectives: Upper extremity deep vein thrombosis (UEDVT) is associated with pulmonary embolism and other complications, but there are no recommendations for UEDVT prophylaxis. The purpose of this study was to establish incidence and risk factors for UEDVT and to determine efficacy of pharmacologic prophylaxis for UEDVT prevention. Methods: For this retrospective cohort study, we identified medical patients aged 18 years and older admitted to 13 Cleveland Clinic hospitals from January 2011 to December 2019. Patients with venous thromboembolism (VTE) on admission, length of stay <1 day, and who received therapeutic anticoagulation were excluded. The potential risk factors included demographics, comorbidities, and medical procedures. Comorbidities were identified via International Classification of Diseases codes, (ICD9 and ICD10), procedures from flowsheets, and prophylaxis from medications administered in the electronic medical record. DVT events were identified by a combination of International Classification of Diseases codes and confirmed by chart review. We performed multivariable logistic regression to identify independent risk factors and the association between VTE prophylaxis and UEDVT. The model's C statistic was obtained using 1000 bootstrap runs. Results: Of 194,809 patients, 496 (0.25% of cohort, 36.8% of all VTE) developed UEDVT by 14 days. In the logistic regression model (bias-corrected C statistic 0.87), 11 risk factors predicted UEDVT, the strongest being peripherally inserted central catheter (odds ratio [OR] 4.62, 95% confidence interval [CI] 3.81-5.60) and central venous catheter (OR 3.57, 95% CI 2.91-4.37). The predicted risk among individuals ranged from 0.02% to 23.4%. Prophylaxiswas negatively associated with the development of UEDVT (OR 0.72, 95% CI 0.60-0.87). Conclusions: UEDVT is rare but some patients are high risk. Therefore, UEDVTrisk factors should be added toVTE risk assessmentmodels, and patients at high risk for UEDVT should receive chemoprophylaxis. [ABSTRACT FROM AUTHOR]

In this study, a long-lived triplet state urea-functionalized carbon nitride (urea-CNx) was successfully synthesized. It possesses a significant specific surface area, an extended excited state lifetime, and a wide band gap and can be used as recyclable and efficient photocatalyst. Urea-CNx was applied for metal-free photo atom transfer radical polymerization (photo-ATRP) of methyl methacrylate as a heterogeneous catalyst without any co-catalysts and it exhibited impressive catalytic activity. It combines both photosensitization and catalytic effects within the ATRP system. The ATRP process utilizing methyl methacrylate as the monomer yields polymers with well-matched molecular weights and narrow PDI (Đ = 1.38) when exposed to blue light irradiation. Good time control and high end group fidelity were demonstrated through intermittent on–off light experiments, precise polymerization of various monomers, and synthesis of block copolymers. The oxygen-tolerant photo-ATRP polymerization was proposed to operate via a reactive oxygen species (ROS)-mediated oxidative quenching pathway mechanism, which was found to significantly enhance the reaction rate of the radical polymerization system. Remarkably, even after 10 cycles, the catalytic efficiency of urea-CNx catalyzed oxygen-tolerant photo-ATRP remained largely unaffected. The system’s advantageous features include being completely metal-free, requiring no cocatalysts, and its good sustainability and “oxygen acceleration” behavior. These features provide a new idea and reliable experimental basis for exploring greener, simpler and more economical photo-ATRP polymerisation processes and applications. [ABSTRACT FROM AUTHOR]

This study aimed to explore the patterns of postoperative recurrence in patients with pT2-3N0M0 esophageal squamous cell carcinoma (ESCC) and to identify the risk factors for the recurrence. Patients with pT2-3N0M0 ESCC who were treated at our hospital from January 2010 to August 2019 were divided into three categories: those with anastomotic recurrence, those with lymph node recurrence, and those with hematogenous metastasis. The sites of initial recurrence and metastasis were counted and potential risk factors were analyzed using univariate and multivariate Cox proportional hazard regression. Four hundred and eighty-five patients with pT2-3N0M0 ESCC were ultimately included, 176 (36.29%) of whom experienced tumor recurrence or metastasis. Cox multivariate analysis revealed that the postoperative T-stage, procedure, tumor location, and degree of differentiation were independent risk factors for postoperative recurrence (P < 0.05). The median time of recurrence was 38 months, and the most common site of recurrence was the lymph nodes in 126 patients (71.59%), followed by hematogenous metastasis in 73 patients (41.47%), and anastomotic recurrence in 21 patients (11.93%). 119 patients (67.61%) experienced recurrence within 36 months, with a probability of recurrence of 84.09% within 5 years, and recurrence remained relatively unchanged after 5 years. The proportion of postoperative lymph node recurrence and hematogenous metastasis in patients with pT3N0M0 ESCC was significantly higher than that in patients with pT2N0M0 ESCC (P < 0.05). At higher tumor locations in the body, the proportion of lymph node recurrence increased (P < 0.05). In conclusion, postoperative T-stage, procedure, tumor location, and degree of differentiation were independent risk factors for postoperative recurrence in pT2-3N0M0 ESCC, with regional lymph node recurrence being the most common pattern, emphasizing the importance of regional lymph nodes in this context. [ABSTRACT FROM AUTHOR]

Rabbit hemorrhagic disease (RHD) causes lethal fulminant hepatitis in rabbits. Two different genotypes (GI.1 and GI.2) responsible for RHD are reported. GI.2 was first detected in France in 2010 and subsequently spread to other countries in Europe. In April 2020, GI.2 was detected in China. In this study, we report a novel recombinant strain of fatal rabbit hemorrhagic disease virus 2 (RHDV2 or GI.2) detected from domestic rabbits in three provinces in China in 2020-2021. Full-length genomic analysis has revealed that the recombinant virus contained an RHDV2 capsid gene and nonstructural genes from an unclassified lagovirus genotype. This type of virus emerged and circulated throughout China within a year after the initial detection of the original RHDV2. Compared with the original strain, the new virus showed a longer infected time and lower mortality rate but almost the same viral load at the moribund stage of infection. This might have resulted in high virus contamination in the environment, facilitating virus transmission. As the consequences of the presence of novel recombinant strains are unpredictable, the circulation of the novel variant in the population should be carefully monitored in China. [ABSTRACT FROM AUTHOR]

Background: Septic shock is the leading cause of acute kidney injury (AKI) in critically ill patients. The foundation of early septic shock management includes early fluid resuscitation, but the association between fluid resuscitation rates and kidney outcomes remains unclear. This investigation examines the association between fluid resuscitation rate and AKI recovery. Methods: In the medical intensive care unit of Mayo Clinic Rochester, adult patients with AKI and septic shock were retrospectively studied from January 1, 2006 to May 31, 2018. The surviving sepsis campaign recommends an initial fluid bolus of 30 ml/kg for sepsis resuscitation. The cohort of patients was divided into three groups based on the average fluid resuscitation time (<1 h, 1.1–3 h, >3 h) and the corresponding fluid rate ≥0.5, 0.17–0.49, and <0.17 ml/kg/min, respectively. The primary outcome was the recovery of AKI on day 7. To account for potential confounders, multivariable regression analyses were conducted. Results: After meeting the eligibility, 597 patients were included in the analysis. The AKI recovery was considerably different among the groups (P = 0.006). Patients in group 1 who received fluid resuscitation faster had a higher rate of AKI recovery (53%) compared to group 2 and group 3 (50% and 37.8%). Conclusion: In septic shock patients with AKI, a higher fluid resuscitation rate of 30ml/kg IV fluids within the 1st‑h sepsis diagnosis(i.e., >0.50 ml/kg/min) lead to higher AKI recovery compared with slower infusion rates. [ABSTRACT FROM AUTHOR]

The article discusses international collaboration, trade, and technological advancements assisting in raising global living standards in Australia. Topics discussed including gradual increased reported cases of racism and xenophobia during the COVID-19 pandemic, 25 percent of teachers in Australia work in schools where 30 percent of the students are from socioeconomically disadvantaged homes, and Australian Curriculum has adopted that all teachers are required to support students.

During an ischemic stroke, the brain releases various factors, including glutamate and γ-aminobutyric acid. Glutamate can cause neurotoxic effects through certain receptors and exacerbate neurological damage, while γ-aminobutyric acid as an inhibitory neurotransmitter can antagonize the excitotoxic effects of glutamate and enhance the tolerance of neurons to ischemia. Therefore, in this study, the content of amino acid neurotransmitters in brain tissue before ischemia, after 10 min of ischemia, hypothermic perfusion, and rewarming were analyzed by high-performance liquid chromatography-UV in an animal model of ischemic stroke generated by blocking the bilateral common carotid arteries of rhesus monkeys. The changes in amino acid neurotransmitters in the rhesus monkey brain during post-ischemia hypothermic perfusion and rewarming were investigated by statistical methods of repeated measures ANOVA, showing that the concentration change of glutamate had not only a temporal factor but also was influenced by temperature, and there was an interaction effect between the two. Time but not temperature affected the change in γ-aminobutyric acid concentration, and there was an interaction effect between the two. Accordingly, hypoperfusion exerts a protective effect during ischemia by inhibiting the release of excitatory amino acid neurotransmitters, while the antagonistic effect of GABA on Glu is not significant. [ABSTRACT FROM AUTHOR]

The accuracy of slope mechanical parameter values determines the accuracy of slope stability assessments and the effectiveness of protective measures. Traditional methods for obtaining geotechnical parameters cannot entirely take into consideration the size, disturbance, variability, and uncertainty of mechanical parameters. Hence, we aimed to propose two algorithmic models for the geotechnical parameters of highway slope materials based on an improved non-dominated sorting genetic algorithm II (NSGA-II) combined with a GA-optimised backpropagation (BP) neural network (NN),named BPGA- NSGA-Ⅱ model and improved BPGA- NSGA-Ⅱ model.The results indicated that compared with the original NSGA-II model, the improved model showed a substantial shift in the Pareto front, and the errors are smaller than the original model.Among the two improved models, the improved BPGA-NSGA-II model has higher inversion accuracy.Therefore, this study provides a scientifically effective method for improving the accuracy of the geotechnical parameter inversion for highway slope materials. [ABSTRACT FROM AUTHOR]

Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (þ)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9μM (ursolic acid as positive control, IC50 - 8.3μM). [ABSTRACT FROM AUTHOR]

The article discusses a study on thermostable ionizable lipid-like nanoparticle (iLAND) as small interfering RNA (siRNA) treatment for hyperlipidemia. It rationally designs a series of ionizable lipid-like materials; and fabricated and evaluated four panels of lipid formulations in four representative structures. It concludes that siRNA@iLAND with thermostable A1-D1-5 offers value for siRNA delivery, hyperlipidemia therapy and prevention of metabolic diseases.

Manganese(II) acetate was reacted with indane-1,2,3-trione-1,2-dioxime (H2L), producing three new MnIII complexes containing a MnIII3O unit. Complex 1 is a zero-dimensional (0D) trinuclear manganese(III) cluster. Complexes 2 and 3 show different two-dimensional (2D) structures with their trinuclear manganese(III) units bridged through Na(I) ions. A study of the magnetic properties manifests that antiferromagnetic coupling is clearly dominant in complexes 1 and 2. In contrast, complex 3 is a single-molecule magnet with dominant ferromagnetic couplings between its metal ions. The Na(I) ions adjust the topologies of these complexes, which thus tunes the magnetic-related parameters such as the Mn-O-N-Mn dihedral angle and finally leads to the achievement of single-molecule magnets. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. METHODS: In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-mg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-mg of mRNA-1653 or placebo. RESULTS: Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-µg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-µg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-µg or 30-µg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; MPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF 5 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. CONCLUSIONS: mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA- 1653 or its components for the prevention of hMPV and PIV3. [ABSTRACT FROM AUTHOR]

When the wind speed changes significantly in a permanent magnet synchronous wind power generation system, the maximum power point cannot be easily determined in a timely manner. This study proposes a maximum power reference signal search method based on fuzzy control, which is an improvement to the climbing search method. A neural network-based parameter regulator is proposed to address external wind speed fluctuations, where the parameters of a proportional-integral controller is adjusted to accurately monitor the maximum power point under different wind speed conditions. Finally, the effectiveness of this method is verified via Simulink simulation. [ABSTRACT FROM AUTHOR]

Large deformation of surrounding rock makes the internal space of a tunnel cannot meet the requirements of normal use after support, even leads to the instability of surrounding rock and destruction of the tunnel structure. In order to optimize the parameters of the primary support to control the deformation of surrounding rock, field tests and numerical simulations are carried out. Based on the engineering geological conditions and the deformation monitoring data of surrounding rock, four important creep parameters of the improved Burgers model are inversed by numerical simulation, considering the creep of surrounding rock in tunnel construction. The results show that it is feasible to use tunnel crown settlement as a control indicator to determine the thickness of shotcrete. Short rock bolts are preferentially used in the tunnel arches, and a combination of long and short rock bolts should be used on the sidewall to control the large deformation of surrounding rock. When the excavation method of upper-lower bench is used in the single-track railway with a relatively large high-span ratio, the horizontal convergence monitoring points of the upper bench are recommended to be set 0.8-0.9 times the height of the upper bench from the tunnel arch crown, and those of the lower bench are recommended to be set 0.6-0.7 times the total height of the upper-lower bench from the tunnel arch crown. [ABSTRACT FROM AUTHOR]

Ground settlement during and after tunnelling using TBM results in varying dynamic and static load action on the geo-stratum. It is an undesirable effect of tunnel construction causing damage to the surface and subsurface infrastructure, safety risk, and increased construction cost and quality issues. Ground settlement can be influenced by several factors, like method of tunnelling, tunnel geometry, location of tunnelling machine, machine operational parameters, depth & its changes, and mileage of recording point from starting point. In this study, a description and evaluation of the performance of the artificial neural network (ANN)was undertaken and a comparison with multiple linear regression (MLR) was carried out on ground settlement prediction. The performance of these models was evaluated using the coefficient of determination R2, root mean square error (RMSE) and mean absolute percentage error (MAPE). For ANN model, the R2, RMSE and MAPE were calculated as 0.9295, 4.2563 and 3.3372, respectively, while for MLR, the R2, RMSE and MAPE, were calculated as 0.5053, 11.2708, 6.3963 respectively. For ground settlement prediction, bothANNandMLRmethodswere able to predict significantly accurate results. It was further noted that the ANN performance was higher than that of the MLR. [ABSTRACT FROM AUTHOR]

Nonlinear compression has become an obligatory technique along with the development of ultrafast lasers in generating ultrashort pulses with narrow pulse widths and high peak power. In particular, techniques of nonlinear compression have experienced a rapid progress as ytterbium (Yb)-doped lasers with pulse widths in the range from hundreds of femtoseconds to a few picoseconds have become mainstream laser tools for both scientific and industrial applications. Here, we report a simple and stable nonlinear pulse compression technique with high efficiency through cascaded filamentation in air followed by dispersion compensation. Pulses at a center wavelength of 1040 nm with millijoule pulse energy and 160 fs pulse width from a high-power Yb:CaAlGdO4 regenerative amplifier are compressed to 32 fs, with only 2.4% loss from the filamentation process. The compressed pulse has a stable output power with a root-mean-square variation of 0.2% over 1 hour. [ABSTRACT FROM AUTHOR]

Context • Osteoarthritis (OA) is a high-incidence, chronic condition, with an extremely high prevalence among older adults. OA seriously compromises the normal living of OA patients, and it’s imperative to find a novel therapy as soon as possible to improve their prognosis and life quality. Objective • The study intended to investigate the therapeutic effects of Curcumin (Cur) on OA and to explore its preliminary mechanism of action, with the aim of offering more accurate guidance for use of OA therapy. Design • The research team designed a prospective nonrandomized controlled trial. Setting • The study took place in the Department of Orthopedics at Sir Run Run Hospital at Nanjing Medical University in Nanjing, China. Participants • Participants were 107 OA patients treated at the hospital between March 2019 and January 2020. Intervention • Participants were divided into two groups, 51 in the Cur group and 56 in the ibuprofen group. Outcome Measures • The clinical efficacy and safety of the two groups were observed. In addition, the research team performed in-vitro studies. Chondrocytes HC-a and C28/I2 were purchased to evaluate the intracellular inflammatory response and apoptosis rate under the intervention of Cur and Wnt/β-catenin pathway inhibitors. Results • No significant differences existed in the clinicalefficacy rate between the two groups (P>.05), but the Cur group show higher improvements in safety, joint mobility, and inhibition of inflammation (P < .05). In-vitro experiments showed that Cur inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/β-catenin inhibitor did the opposite (P<.05). Conclusions • Cur can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/β-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes. [ABSTRACT FROM AUTHOR]

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single-cell RNA-Seq, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validations of 2 isoform switching events in CERS5 and MPZL1 show regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in affecting glioma malignancy and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas. [ABSTRACT FROM AUTHOR]

The article discusses the comparison between ketamine and electroconvulsive therapy (ECT) for the treatment of non-psychotic, treatment-resistant major depression. It mentions several letters raise concerns and questions regarding the study's methodology, including the use of unilateral ECT, concurrent medications, and patient characteristics, suggesting that the trial may not give ECT a fair comparison.

Background: Mufangji tang (MFJT) is composed of Ramulus Cinnamomi, Radix Ginseng, Cocculus orbiculatus (Linn.) DC., and Gypsum. In clinical settings, MFJT has been effectively employed in addressing a range of respiratory disorders, notably including pulmonary arterial hypertension (PAH). However, the mechanism of action of MFJT on PAH remains unknown. Methods: In this study, a monocrotaline-induced PAH rat model was established and treated with MFJT. The therapeutic effects of MFJT on PAH rat model were evaluated. Network pharmacology was conducted to screen the possible targets for MFJT on PAH, and the molecular docking between the main active components and the core targets was carried out. The key targets identified from network pharmacology were tested. Results: Results showed significant therapeutic effects of MFJT on PAH rat model. Analysis of network pharmacology revealed several potential targets related to apoptosis, inflammation, oxidative stress, and vascular remodeling. Molecular docking showed that the key components were well docked with the core targets. Further experimental validation results that MFJT treatment induced apoptosis (downregulated Bcl-2 levels and upregulated Bax levels in lung tissue), inhibited inflammatory response and oxdative stress (decreased the levels of IL-1β, TNF-α, inducible NOS, and malondialdehyde, and increased the levels of endothelial nitric oxide synthase, nitric oxide, glutathione and superoxide dismutase), reduced the proliferation of pulmonary arterial smooth muscle cells (downregulated ET-1 and β-catenin levels and ERK1/2 phosphorylation, increased GSK3β levels). Conclusion: Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis, inhibition of inflammation and oxidative stress, and the prevention of vascular remodeling. [ABSTRACT FROM AUTHOR]

The air quality in China has changed due to the implementation of clean air actions since 2013. Evaluating the spatial pattern of PM2.5 and the effectiveness of reducing anthropogenic emissions in urban and nonurban areas is crucial. Therefore, the China Long-term Air Pollutant dataset for PM2.5 (CLAP_PM2.5) was generated from 2010 to 2022 with a daily 0.1° resolution using the random forest model and integrating multiple data sources, including extensive in-situ PM2.5 measurements, visibility, satellite retrievals, surface and upper-level meteorological data and other ancillary data. The CLAP_PM2.5 dataset is more reliable and accurate than other public datasets. Analysis of CLAP_PM2.5 from 2010 to 2022 reveals the decrease in positive urban-nonurban PM2.5 differences and higher decreasing rates of PM2.5 in most city clusters in eastern China. Furthermore, separating meteorological and emission contributions to the PM2.5 variability by a meteorological normalization approach indicates that meteorological contribution gradually changed from unfavorable to PM2.5 reduction during 2013-2017 to favorable to decline enhancement during 2018-2022, and in urban regions, meteorological contribution is higher than that in nonurban areas. Overall, the reduction in deweathered PM2.5 concentrations highlights China's significant achievements in terms of comprehensive clean air actions. [ABSTRACT FROM AUTHOR]

Five-membered pyrroline nitroxides with high-potential is fascinating as catholyte for aqueous organic redox flow batteries (AORFBs), however, it suffers from a primary deficiency of insufficient stability due to ring-opening side reaction. Herein we report a spatial structure regulation strategy by host-guest chemistry, encapsulating 3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl (CPL) into hydrosoluble cyclodextrins (CDs) with an inclusion structure of N-O· head towards cavity bottom, to boost the solubility and cyclability of pyrroline nitroxides significantly. The armor-clad CPL (CPL⊂HP-β-CD) catholyte in 0.05-0.5 M presents a battery capacity fade rate as low as 0.002 %/cycle (0.233 %/day) compared to the sole CPL in 0.05 M (0.039 %/cycle or 5.23 %/day) over 500 cycles in assembled AORFBs. The optimized reclining spatial structure with N-O· head towards CD cavity bottom effectively inhibits the attack of Lewis base species on the hydrogen abstraction site in pyrroline ring, and thus avoids the ring-opening side reaction of pyrroline nitroxides. [ABSTRACT FROM AUTHOR]

Plants produce various pigments that not only appear as attractive colors but also provide valuable resources in applications in daily life and scientific research. Biosynthesis pathways for these natural plant pigments are well studied, and most have multiple enzymes that vary among plant species. However, adapting these pathways to animals remains a challenge. Here, we describe successful biosynthesis of betalains, water-soluble pigments found only in a single plant order, Caryophyllales, in transgenic silkworms by coexpressing three betalain synthesis genes, cytochrome P450 enzyme CYP76AD1, DOPA 4,5-dioxygenase, and betanidin 5-O-glucosyltransferase. Betalains can be synthesized in various tissues under the control of the ubiquitous IE1 promoter but accumulate mainly in the hemolymph with yields as high as 274 μg/ml. Additionally, transformed larvae and pupae show a strong red color easily distinguishable from wild-type animals. In experiments in which expression is controlled by the promoter of silk gland-specific gene, fibroin heavy-chain, betalains are found predominantly in the silk glands and can be secreted into cocoons through spinning. Betalains in transformed cocoons are easily recovered from cocoon shells in water with average yields reaching 14.4 μg/mg. These data provide evidence that insects can synthesize natural plant pigments through a complex, multiple enzyme-mediated synthesis pathway. Such pigments also can serve as dominant visible markers in insect transgenesis applications. This study provides an approach to producing valuable plant-derived compounds by using genetically engineered silkworms as a bioreactor. [ABSTRACT FROM AUTHOR]

Towards the end of 2019, a novel coronavirus pneumonia (coronavirus disease 19, COVID-19) caused by SARS-CoV-2 infection emerged in Wuhan. The SARS-CoV-2 virus quickly spread across the globe, seriously affecting public health and economic development of countries worldwide. Currently, antiviral drugs developed for COVID-19 lack strong clinical trial support and the high mutation rate of the virus causes difficulties in vaccine development, thus a complex and delayed large scale role out of an efficacious vaccine. Traditional Chinese medicine (TCM) has been used for treating various conditions for thousands of years and has a unique systems theory. It can be individualized into specific therapeutic regimens according to the patients' physical condition, clinical symptoms, and other distinguishing factors. In addition, TCM often has different effects at different disease stages, thus contributing to disease prevention, treatment, and rehabilitation. Existing evidence shows that TCM has efficacy in the treatment of COVID-19. The active ingredients of TCM have various pharmacological properties, including antiviral, anti-inflammatory, and immunomodulatory activity, with clinical trials showing that these prescriptions reduce symptoms of COVID-19, promote viral clearance, and ultimately improve survival in infected patients. This article discusses the advantages and mechanisms of TCM in the treatment of COVID-19, hoping to provide a reference platform in the fight against the disease. [ABSTRACT FROM AUTHOR]

Introduction: Admission hyperglycemia is a common finding after spontaneous intracerebral hemorrhage (ICH) secondary to pre-existing diabetes mellitus (DM) or stress-induced hyperglycemia (SIH). Studies of the causal relationship between SIH and ICH outcomes are rare. Aim: We aimed to identify whether SIH or pre-existing DM was the cause of admission hyperglycemia associated with ICH outcomes. Methods: Admission glycosylated hemoglobin (HbA1c), glucose levels, and comorbidity data from the prospective, multicenter cohort, Chinese Cerebral Hemorrhage: Mechanisms and Intervention Study (CHEERY), were collected and analyzed. According to different admission blood glucose and HbA1c levels, patients were divided into nondiabetic normoglycemia (NDN), diabetic normoglycemia (DN), diabetic hyperglycemia (DH), and SIH groups. Modified Poisson regression models were used to analyze ICH outcomes in the different groups. Results: In total, 1372 patients were included: 388 patients with admission hyperglycemia, 239 with DH, and 149 with SIH. In patients with hyperglycemia, SIH was associated with a higher risk of pulmonary infection [risk ratios (RR): 1.477, 95% confidence interval (CI): 1.004–2.172], 30-day (RR: 1.068, 95% CI: 1.009–1.130) and 90- day mortality after ICH (RR: 1.060, 95% CI: 1.000–1.124). Conclusions: Admission hyperglycemia is a common finding after ICH, and SIH is a sensitive predictor of the risk of pulmonary infection and all-cause death after ICH. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the imaging characteristics of Xp11.2/TFE3 translocation renal cell carcinoma and explore the relationship between the pathological features and imaging findings. Materials and Methods: Imaging, pathological, and clinical data of 28 patients with Xp11.2 RCC were studied from August 2013 to November 2019. The imaging characteristics and morbidity of different group were also explored meanwhile. Results: Patients ranged from 3 to 83 years old and the median age was 47 years. Bilateral renal tumors were detected in 1 patient and unilateral in the rest 27 patients. Out of 29 tumors, 13 were in the left kidneys and 16 in the right. Tumor size ranged from 2.2 cm × 2.5 cm to 20.0 cm × 9.7 cm. Tumors were cystic component/necrosis (29/29,100%), renal capsule breakage (16/29, 55%), capsule (18/29, 62%), calcification (15/29, 52%), fat (4/29, 14%), and metastasis (10/29, 34%). Tumors showed moderate enhancement during renal corticomedullary phase and delayed enhancement during nephrographic and excretory phase. The solid parts showed hypointense on T2WI. The imaging characteristics did not have significant correlation with the age, the incidence of adolescent and children group was higher than adult group. Conclusion: Xp11.2 RCC is a well‑defined mass with cystic component, the solid part of tumor showed hypointense on T2WI. Xp11.2 RCC showed moderate enhancement during the renal corticomedullary phase and delayed enhancement during the nephrographic phase and excretory phase. Xp11.2 RCC has a higher incidence in children. [ABSTRACT FROM AUTHOR]

The combination of SSP eye drop and anti-vascular endothelial growth factor (VEGF) injection showed approximately two times better therapeutic effect over anti-VEGF treatment alone. B Smart Supramolecular Peptides b In article number 2203351, Lei Wang, Hao Wang, Bo Hu, and co-workers report the formulation of a smart supramolecular peptide (SSP) eye drop for diabetic retinopathy treatment that is effective via specifically identifying and capturing Semaphorin4D (Sema 4D), a strongly pro-angiogenesis and exudates factor. [Extracted from the article]

Although recent studies have revealed an involvement of hippocampal interneurons in learning the association among timeseparated events, its underlying cellular mechanisms remained not fully clarified. Here, we combined multichannel recording and optogenetics to elucidate how the hippocampal parvalbumin-expressing interneurons (PV-INs) support associative learning. To address this issue, we trained the mice (both sexes) to learn hippocampus-dependent trace eyeblink conditioning (tEBC) in which they associated a light flash conditioned stimulus (CS) with a corneal air puff unconditioned stimuli (US) separated by a 250 ms time interval. We found that the hippocampal PV-INs exhibited learning-associated sustained activity at the early stage of tEBC acquisition. Moreover, the PV-IN sustained activity was positively correlated with the occurrence of conditioned eyeblink responses at the early learning stage. Suppression of the PV-IN sustained activity impaired the acquisition of tEBC, whereas the PV-IN activity suppression had no effect on the acquisition of delay eyeblink conditioning, a hippocampus-independent learning task. Learning-associated augmentation in the excitatory pyramidal cell-to-PVIN drive may contribute to the formation of PV-IN sustained activity. Suppression of the PV-IN sustained activity disrupted hippocampal gamma but not theta band oscillation during the CS-US interval period. Gamma frequency (40 Hz) activation of the PV-INs during the CS-US interval period facilitated the acquisition of tEBC. Our current findings highlight the involvement of hippocampal PV-INs in tEBC acquisition and reveal insights into the PV-IN activity kinetics which are of key importance for the hippocampal involvement in associative learning. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a detrimental neurological disease characterized by an irreversible infarct core surrounded by an ischemic penumbra, a salvageable region of brain tissue. Unique roles of distinct brain cell subpopulations within the neurovascular unit and peripheral immune cells during ischemic stroke remain elusive due to the heterogeneity of cells in the brain. Single-cell RNA sequencing (scRNA-seq) allows for an unbiased determination of cellular heterogeneity at high-resolution and identification of cell markers, thereby unveiling the principal brain clusters within the cell-type-specific gene expression patterns as well as cellspecific subclusters and their functions in different pathways underlying ischemic stroke. In this review, we have summarized the changes in differentiation trajectories of distinct cell types and highlighted the specific pathways and genes in brain cells that are impacted by stroke. This review is expected to inspire new research and provide directions for investigating the potential pathological mechanisms and novel treatment strategies for ischemic stroke at the level of a single cell. [ABSTRACT FROM AUTHOR]

Purpose: To determine the treatment efficacy of the combination of loxoprofen sodium and sodium hyaluronate in osteoarthritis (OA), and its role in knee joint function. Methods: 98 patients with OA admitted to Guang'an People's Hospital, Sichuan, China were allocated into control group (CNG, given loxoprofen sodium n, = 51) and study group (SG, given loxoprofen sodium and sodium hyaluronate, n = 47). Both groups were compared in terms of the levels of inflammatory factor, Lysholm, VAS, WOMAC scores, treatment effects, serum MDA, NO, SOD levels, adverse effects, and blood rheology indices. Results: The study group had higher SOD levels, and higher BALP and BGP than CNG (p < 0.05). SG had lower TRACP-5b and blood rheological indices than CNG (p < 0.05). The difference in the incidence of adverse reactions was not statistically significant between the two groups (p > 0.05). Conclusion: The combination of loxoprofen sodium and sodium hyaluronate effectively improves the function and blood rheological indices of knee joints. It reduces the occurrence of adverse reactions and the level of pain in patients with OA, and improves OA prognosis. However further clinical trials are required prior to application in clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses Temozolomide (TMZ)-resistant aggressive brain cancer glioblastoma (GBM) has guanine mutations that disrupt the G-rich DNA G4s and splice sites that lead to deregulated alternative splicing. It mentions alterations create vulnerabilities, which are selectively targeted by either the G4-stabilizing drug TMPyP4 or a novel splicing kinase inhibitor of cdc2-like kinase. It also mentions vulnerabilities of TMZ-resistant GBM and present cytoplasmic EWSR1 as a putative biomarker.

The Porphyromonas gingivalis type IX secretion system (T9SS) promotes periodontal disease by secreting gingipains and other virulence factors. By in situ cryoelectron tomography, we report that the P. gingivalis T9SS consists of 18 PorM dimers arranged as a large, caged ring in the periplasm. Near the outer membrane, PorM dimers interact with a PorKN ring complex of ∼52 nm in diameter. PorMKN translocation complexes of a given T9SS adopt distinct conformations energized by the proton motive force, suggestive of different activation states. At the inner membrane, PorM associates with a cytoplasmic complex that exhibits 12-fold symmetry and requires both PorM and PorL for assembly. Activated motors deliver substrates across the outer membrane via one of eight Sov translocons arranged in a ring. The T9SSs are unique among known secretion systems in bacteria and eukaryotes in their assembly as supramolecular machines composed of apparently independently functioning translocation motors and export pores. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to clone and compare the molecular characteristics of the deiodinase 2 (DIO2) gene between Sichuan White geese and Landes geese, and to analyze the association between polymorphisms of the DIO2 gene and head dimensions in Tianfu meat geese. Methods: The coding sequence of the DIO2 gene was cloned by polymerase chain reaction and vector ligation and aligned by DNAMAN software. A total of 350 Tianfu meat geese were used to genotype the polymorphisms of the DIO2 gene and measure the head dimensions. Association analysis between the polymorphisms of the DIO2 gene and head dimensions was carried out. Results: An 840-bp coding sequence of the DIO2 gene was obtained and comparison analysis identified four polymorphic loci between Sichuan White geese and Landes geese. Further analysis showed that the dominant alleles for the four polymorphic loci were G, G, A, and T and the frequency of the heterozygous genotype was higher than that of the homozygous genotype in Tianfu meat geese. Compared to that in the population of non-knob geese of Tianfu meat geese, the head dimensions in the population of knob geese were significantly higher except for nostril height. However, in the non-knob geese, beak width 1, beak width 2, nostril length, cranial width 1, and maxillary length had significant differences among different genotypes or haplotypes/diplotypes. Conclusion: These results suggested that polymorphisms of the DIO2 gene could be considered molecular markers to select larger heads of geese in the population of non-knob geese. [ABSTRACT FROM AUTHOR]

One Health is a collaborative, multi-sectoral, trans-disciplinary approach with the goal of achieving optimal health outcomes by recognizing the interconnection between people, animals, plants, and the environment and determining how this relates to the control of infectious diseases such as malaria, schistosomiasis and so on. Malarias caused by Plasmodium that commonly infects female Anopheles mosquitoes, which feed on human blood and act as a disease vector. It has been a worldwide important public health problem from ancient times. Also, malaria is one of the infectious diseases with the longest epidemic time and the most serious harm in the history of Henan Province, China. During the past decades, the multi-sectoral, cross-regional, and multi-disciplinary One Health approach contributed to a significant reduction in malaria incidence, resulting in initiation of the Henan Malaria Elimination Action Plan. Herein, we reviewed the history of the fight against malaria in Henan Province. A full picture of malaria epidemics, prevention, and control strategies were showed, with the objective that it will help stakeholders, and policy-makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in the similar areas. [ABSTRACT FROM AUTHOR]

Interleukin-1α (IL-1α) plays an important role in inflammation and hematopoiesis. Many tumors have increased IL-1α expression. However, the immune regulatory role of secreted IL-1α in tumor development and whether it can be targeted for cancer therapy are still unclear. Here, we found that tumoral-secreted IL-1α significantly promoted hepatocellular carcinoma (HCC) development in vivo. Tumoral-released IL-1α were found to inhibit T and NK cell activation, and the killing capacity of CD8+ T cells. Moreover, MDSCs were dramatically increased by tumoral-released IL-1α in both spleens and tumors. Indeed, higher tumoral IL-1α expression is associated with increased tumoral infiltration of MDSCs in HCC patients. Further studies showed that tumoral-released IL-1α promoted MDSC recruitment to the tumor microenvironment through a CXCR2-dependent mechanism. Depletion of MDSCs could diminish the tumor-promoting effect of tumoral-released IL-1α. On the contrary, systemic administration of recombinant IL-1α protein significantly inhibited tumor development by activating T cells. In fact, IL-1α protein could promote T cell activation and enhance the cytotoxicity of CD8+ T cells in vitro. Thus, our study demonstrated that tumoral-released IL-1α promoted tumor development through recruiting MDSCs to inhibit T cell activation, while systemic IL-1α directly promoted anti-tumor T cell responses. We further identified calpain 1 as the major intracellular protease mediating tumoral IL-1α secretion. Calpain 1 KO tumors had diminished IL-1α release and reduced tumor development. Thus, our findings provide new insights into the functions of secreted IL-1α in tumor immunity and its implications for immunotherapy. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) are a disorder of cerebral microvessels that are characterized as small (<10 mm), hypointense, round or ovoid lesions seen on T2*-weighted gradient echo MRI. There is a high prevalence of CMBs in community-dwelling healthy older people. An increasing number of studies have demonstrated the significance of CMBs in stroke, dementia, Parkinson's disease, gait disturbances and late-life depression. Blood-brain barrier (BBB) dysfunction is considered to be the event that initializes CMBs development. However, the pathogenesis of CMBs has not yet been clearly elucidated. In this review, we introduce the pathogenesis of CMBs, hypertensive vasculopathy and cerebral amyloid angiopathy, and review recent research that has advanced our understanding of the mechanisms underlying BBB dysfunction and CMBs presence. CMBs-associated risk factors can exacerbate BBB breakdown through the vulnerability of BBB anatomical and functional changes. Finally, we discuss potential pharmacological approaches to target the BBB as therapy for CMBs. [ABSTRACT FROM AUTHOR]

Fungal pre-treatment and fermentation could improve nutritional value of wet corn distillers’ grains and solubles (WDGS), soybean hull (SH), and their blend in swine and poultry diets, which can potentially increase revenues for corn-ethanol and soybean processing industries while reducing feed cost in swine and poultry production systems. This study evaluated the effectiveness of pre-treatment of SH, WDGS, and their mixture by Trichoderma reesei and fermentation by Aspergillus oryzae to improve the nutritional profile and digestibility of these ingredients. T. reesei produced cellulase and xylanase, resulting in structural carbohydrates reduction by 69.2% while concentrating amino acids from 6.8% to 11% in SH. Fermentation with A. oryzae degraded phytate by over 50% and improved in vitro digestibility of amino acids in WDGS and its mixture with SH. Fermenting T. reesei pre-treated SH by A. oryzae showed higher in vitro dry matter digestibility than non-fermented substrate. Moreover, the proportion of key amino acids (arginine, threonine, methionine, and lysine) in both T. reesei and A. oryzae fermented substrates were significantly improved. The results demonstrated the feasibility of combining T. reesei and A. oryzae in improving feeding value of WDGS and SH for potential use as feed ingredients for monogastric animals. [ABSTRACT FROM AUTHOR]

Corn wet distiller’s grain with solubles (WDGS) used as a feeding ingredient to monogastric animal diets is limited due to its imbalanced key amino acids, high fiber and potential existance of mycotoxins. Fermentation of WDGS by edible fungi has potential of upgrading the feedstock into nutritional and low-risk feeding ingredient for monogastric animals. In this study, four different fungi Aspergillus oryzae, Rhizopus oryzae, Mucor indicus and Trichoderma reesei were employed to ferment the mixture of WDGS and soybean hull at 75/25 ratio at 28 °C for 6–9 days. Urea at different concentration was supplied as additional nitrogen source. Results showed that, M. indicus improved total amino acids yield by 13.3% with over 95% consumption of the supplied urea at 1% N. Meanwhile, T. reesei degraded structural polysaccharides by 41% and concentrated amino acids by 19%. In addition, phytate was degraded by 53, 56, 31 and 20% with A. oryzae, R. oryzae, M. indicus, and T. reesei, respectively. Total aflatoxin and deoxynivalenol was detoxified via T. reesei by 52.8% and 92.9%, respectively, while zaeralenone was detoxified via M. indicus by 89.2%. This study demonstrated a feasible way of producing nutritional-improved monogastric feeding ingredient from corn-ethanol plant. [ABSTRACT FROM AUTHOR]

Due to the emergence of new network attack technologies, cloud manufacturing platforms may be subject to various network attacks at any time. Traditional network attack prediction aims to predict the upcoming types of network attacks with monitored data characteristics, and this prediction method cannot accurately learn the network attack traffic that the cloud manufacturing platform may suffer in the future. Network attack traffic prediction means the future network attack traffic prediction by using past data. Traditional machine learning approaches cannot investigate complex nonlinear features. Deep learning methods can investigate nonlinear characteristics, yet they suffer from the problem of overfitting. In addition to this, deep learning approaches suffer from gradient disappearance and explosion. To solve them, we design a network attack traffic method called S-Informer, which integrates the filter of Savitzky–Golay, the self-attention of ProbSparse in a generative decoder and an encoder for eliminating noise, reducing the network scale and improving the speed of prediction. Real-life dataset-based experimental results show that S-Informer achieves higher prediction accuracy than several commonly-used algorithms. [Display omitted] • A hybrid network attack detection method is given for a cloud manufacturing platform. • It adopts a Savitzky–Golay filter for data smoothing and noise elimination. • It adopts a self-attention mechanism of an encoder to reduce network scale. • It adopts a generative style decoder for prediction speed improvement. • A real-life dataset is used to show the accuracy of the prediction of the S-Informer. [ABSTRACT FROM AUTHOR]