An Arabidopsis Rab18 GTPase promotes autophagy by tethering ATG18a to the ER in response to nutrient starvation.

The expansion of autophagosomes requires a controlled association with the endoplasmic reticulum (ER). However, the mechanisms governing this process are not well defined. In plants, ATG18a plays a key role in autophagosome formation in response to stress, yet the factors regulating the process are unknown. This study finds that ATG18a acts as a downstream effector of RABC1, a member of the poorly characterized Rab18/RabC GTPase subclass in plants. Active RABC1 interacts with ATG18a on the ER, particularly under nutrient starvation. In rabc1 mutants, autophagy is compromised, especially under nutrient deprivation, affecting the ER association and expansion of ATG18a-positive autophagosomes. Furthermore, both dominant-negative and constitutively active RABC1 forms inhibit autophagy. The dominant inactive RABC1 impedes the ER association of ATG18a, whereas the constitutively active RABC1 delays ATG18a detachment from the ER. Collectively, RABC1 regulates the ER association and the subsequent detachment of ATG18a-positive autophagosomes during nutrient starvation.

Plexiform Schwannoma of Brachial Plexus in Axilla: A Rare Case Report.

The most common tumours in the brachial plexus are benign schwannomas, followed by neurofibromas and malignancies, originating from the peripheral nerve sheath. The clinical manifestations of brachial plexus tumours are variable according to their location, extension, neurological elements involved and pathology. Brachial plexus tumours are rare in the upper extremity, and axillary schwannoma is uncommon. This case reports a 59-year-old woman with a tumour in her left axilla for two years, gradually enlarging with numbness in her left little finger. Microsurgical interfascicular dissection operation was performed to remove the tumour. Νumbness disappeared after the procedure, and no tumour recurrence was observed during the 30-month follow-up. To the best of our knowledge, plexiform schwannoma of the brachial plexus in the axilla has not been reported so far. In this article, such a case is reported, where this tumour was diagnosed by the histopathological examination and confirmed with immunohistochemistry.

Microsurgical interfascicular dissection operation is a viable treatment of carpal tunnel syndrome caused by Lipofibromatous hamartoma: A case report.

Lipofibromatous Hamartoma (LFH) is a rare and slow growing benign tumor affecting the peripheral nerves, which usually involves the median nerve. Median nerve involvement commonly causes pain, numbness, paresthesia and carpal tunnel syndrome (CTS). This article describes a case of lipofibromatous hamartoma in a 6-years-old girl, complained of the mass and numbness in her left distal forearm. Microsurgical interfascicular dissection operation was performed to remove the epineural proliferation tissue, numbness disappeared after the operation. At the 12-months follow-up appointment she remained asymptomatic and there was no change in mass size.

Affordable phosphor-converted LEDs with specific light quality facilitate the tobacco seedling growth with low energy consumption in Industrial Seedling Raising.

Industrial Seedling Raising (ISR) is increasingly becoming an important part of Modern Agriculture because of its efficient utilization of land, water, and fertilizer as well as its advantages of being not easily affected by the weather. However, the high cost and high energy consumption of light sources for plant growth is limiting the popularization of ISR technology. Phosphor-converted light-emitting diodes (pc-LEDs) make use of relatively affordable red phosphor and blue light chips, providing an adjustable spectrum to optimize plant growth. To identify the energy-saving light quality of pc-LEDs, we investigated the effects of a variety of light qualities on the growth of tobacco seedlings. Y3Al5O12:Ce3+, CaAlSiN3:Eu2+, KAl11O17:Eu2+ phosphors were combined with the blue light chip according to different proportions to produce the following light sources: CK (white light), T1 (blue light), T2 (red light), T3 (red: blue light ratio = 1:4), T4 (red: blue light ratio = 4:1). The tobacco variety Xiangyan7 grown continuously under T1, T2, T3, and T4 significantly increased the leaf area, stem length, biomass, root area and main root length compared with those grown under white light. Among the five kinds of light qualities tested, T4 treatment exerted the best effect on leaf development and biomass increase, while T2 exerted the best effect on stem elongation. The cytological analysis demonstrated that the promotion of the cell size and cell number of leaf epidermal cells by T1-T4 might contribute to the leaf expansion. Further analysis at the molecular level suggested that the light quality affected the RNA levels of the genes involved in cell division and expansion. When tobacco seedlings reached the same biomass, T1-T4 light sources saved 71%, 86%, 80% and 89% of electric energy respectively compared with white light. Therefore, the application of specific pc-LEDs not only reduces the cost of light source production, but also saves energy consumption, offering great potential for ISR technology to cut costs and increase efficiency.

Brain networks under uncertainty: A coordinate-based meta-analysis of brain imaging studies.

In recent years, uncertainty has been extensively studied as a core factor in anxiety models. However, it remains unclear whether there is a stable brain circuitry to cope with uncertainty. Addressing this yet open question, we first distinguish uncertainty into three different states: risky, ambiguity, and threat anticipation. Then, we performed three meta-analyses of fMRI studies to identify those regions that are commonly activated by the three domains using activation likelihood estimation (ALE). The overlapping analyses of the three ALE maps revealed major conjunctions of the risk decision making, ambiguity decision making, and the threat anticipation in specifically the right insula. Contrast analysis further confirmed this finding. In addition, different uncertainty states also have different brain networks involved. Specifically, a large number of brain regions in the frontal-parietal cortex were recruited under ambiguity state, while subcortical gray matter regions were recruited under risk decision making, and the bilateral insula were closely associated with threat anticipation. Additionally, we assessed the co-activation pattern of identified regions using meta-analytic connectivity modeling (MACM) to investigate the potential network underlying the relationship of three domains. The MACM analysis further confirmed that different uncertain states have specific brain network basis. We concluded that the right insula serves as a convergent brain region for brain regions recruited for different uncertain states, and its co-activation pattern also corresponds to the brain network of the three uncertain states. This study is a preliminary attempt to further uncover the brain circuitry of anxiety models with uncertainty at their core.

Predicting mortality from intracranial hemorrhage in patients who undergo allogeneic hematopoietic stem cell transplantation.

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, a total of 70 allo-HSCT patients with an ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with an ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. These 2 cohorts were used to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors (lactate dehydrogenase level, albumin level, white blood cell count, and disease status) were retained in the multivariable logistic regression model, and a simplified grading scale (termed the LAWS score) was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, P > .05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic, 0.859; 95% confidence interval, 0.776-0.945) and the external validation cohort (C-statistic, 0.795; 95% confidence interval, 0.645-0.945). The LAWS score is the first scoring system capable of predicting 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.

VEGF Antagonism Attenuates Cerebral Ischemia/Reperfusion-Induced Injury via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.

Endoplasmic reticulum (ER) stress-mediated apoptosis pathway is considered to play a vital role in mediating stroke and other cerebrovascular diseases. Previous studies have showed that vascular endothelial growth factor (VEGF) antagonism reduced cerebral ischemic-reperfusion (CI/R) damage, but whether attenuation of ER stress-induced apoptosis is contributing to its mechanisms remains elusive. Our study aimed to investigate the protective effect of VEGF antagonism on CI/R-induced injury. First, oxygen-glucose deprivation and re-oxygenation (OGD/R) BEND3 cell model was constructed to estimate small interfering RNA (siRNA)-VEGF on damage of endothelial cells. Next, in animal model, CI/R mice were induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion to investigate cerebral tissue damage. For treatment group, mice received 100 µg/kg anti-VEGF antibodies at 30 min before MCAO, followed by 24 h reperfusion. Our findings demonstrated that pre-administration of siRNA-VEGF before OGD/R changed the biological characteristics of BEND3 cells, reversed the levels of X-box binding protein-1 (XBP-1) and glucose-regulated protein 78 (GRP78), showing siRNA-VEGF attenuated, at least in part, the oxidative damage in OGD/R cell by down-regulating ER stress. In mice experiment, pre-administration of anti-VEGF antibody reduced the brain infarct volume and edema extent and improved neurological scores outcome of CI/R injury mice. Pathological and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining results also confirmed this protective effect. The expressions of VEGF, CATT/EBP homologous protein (CHOP), inositol requiring enzyme 1α (IRE-1α), and cleaved-caspase12 and c-jun N-terminal kinase (JNK) phosphorylation were also prominently decreased. These results suggested that inhibition of endogenous VEGF attenuates CI/R-induced injury via inhibiting ER stress-mediated apoptosis.

Bone Marrow-Derived Mesenchymal Stem Cells Modified with Akt1 Ameliorates Acute Liver GVHD.

BACKGROUND: Liver injury associated with acute graft-versus-host disease (aGVHD) is a frequent and severe complication of hematopoietic stem cell transplantation and remains a major cause of transplant-related mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) has been proposed as a potential therapeutic approach for aGVHD. However, the therapeutic effects are not always achieved. In this study, we genetically engineered C57BL/6 mouse BM-MSCs with AKT1 gene and tested whether AKT1-MSCs was superior to control MSCs (Null-MSCs) for cell therapy of liver aGVHD. RESULTS: In vitro apoptosis analyses showed that, under both routine culture condition and high concentration interferon-γ (IFN-γ) (100ng/mL) stimulation condition, AKT1-MSCs had a survival (anti-apoptotic) advantage compared to Null-MSCs. In vivo imaging showed that AKT1-MSCs had better homing capacity and longer persistence in injured liver compared to Null-MSCs. Most importantly, AKT1-MSCs demonstrated an enhanced immunomodulatory function by releasing more immunosuppressive cytokines, such as IL-10. Adoptive transfer of AKT1-MSCs mitigated the histopathological abnormalities of concanavalin A(ConA)-induced liver injury along with significantly lowered serum levels of ALT and AST. The attenuation of liver injury correlated with the decrease of TNF-α and IFN-γ both in liver tissue and in the serum. CONCLUSIONS: In summary, BM-MSCs genetically modified with AKT1 has a survival advantage and an enhanced immunomodulatory function both in vitro and in vivo and thus demonstrates the therapeutic potential for prevention and amelioration of liver GVHD and other immunity-associated liver injuries.

Transabdominal ultrasound-guided multifetal pregnancy reduction in 10 cases of monkeys.

Intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) in nonhuman primates, e.g. rhesus and cynomolgus monkeys, has been widely used in researches of reproductive and developmental biology, and the success rate has been improved significantly. However, unwanted multiple pregnancy occurs frequently during the ICSI-ET in monkeys, most of which leads to miscarriages. To improve the birth rate of pregnancies and to safeguard health of host and baby monkeys, multifetal pregnancy reduction (MPR) is necessary. In this study, a total of 10 monkeys with multiple pregnancies received MPR through transabdominal ultrasound-guided potassium chloride injection into beating hearts of selective fetuses. To assess MPR efficiency, 31 monkeys with normal singleton pregnancies and 25 monkeys with twin pregnancies without MPR were used as controls. The aim of the reduction is to keep only one fetus, no matter twin or triplet pregnancy originally. Our results show that six cases of MPR were successful and all of them retained single fetus. Moreover, about 1 month (30.2 ± 1.2 days) of gestation is a better timing for MPR than later stage (50.7 ± 1.9 days). We also found that the remaining fetuses developed normally with full-term gestation and normal birth weight. In conclusion, transabdominal ultrasound-guided potassium chloride injection is a safe and effective MPR method for monkeys with multiple pregnancies.

[FBG Self-Chirped Based on an Sine-Structure].

Considerting that the uniform grating can be induced chirp effect under non-uniform strain, a method of making chirp grating by uniform grating with the use of sine structure is proposed. The sine structure was designed as basal material while the fiber Bragg and grating was pasted in the strain non-uniform area of basal material. the strain it produced was introducied into FBG gate area by applying tensile load to achieve FBG produce chirp effect. FBG was made with multiple peaks and wide bandwidth of the chirp grating. The finite element software was used to simulate the strain of sine-structure under tensile loading to get strain contours of the sinusoidal structure in different positions; The experimental results showd that the bandwidth has been increased five times when the displacement load was up to 8 mm and the chirp grating reflection spectrum with multiple peaks; The transfer matrix method to reflection spectrum of chirp grating was combined for spectrum simulation reconstruction and the simulation spectrum spectrum trend was consistent with the experimental results. The chirp grating made in this method has an important application in complex strain field multiple parameters and achieving sense of temperature without compensation by the use of the bandwidth of the chirp grating at the same time.