Levels Of PF Research Articles

Abnormality in Peripheral and Brain Iron Contents and the Relationship with Grey Matter Volumes in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of "MCCA+jICA" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the "MCCA+jICA" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from "MCCA+jICA" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.

Interaction between Kölliker-Fuse/A7 and the parafacial respiratory region on the control of respiratory regulation

Respiration is regulated by various types of neurons located in the pontine-medullary regions. The Kölliker-Fuse (KF)/A7 noradrenergic neurons play a role in modulating the inspiratory cycle by influencing the respiratory output. These neurons are interconnected and may also project to brainstem and spinal cord, potentially involved in regulating the post-inspiratory phase. In the present study, we hypothesize that the parafacial (pF) neurons, in conjunction with adrenergic mechanisms originating from the KF/A7 region, may provide the neurophysiological basis for breathing modulation. We conducted experiments using urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats. Injection of L-glutamate into the KF/A7 region resulted in inhibition of inspiratory activity, and a prolonged and high-amplitude genioglossal activity (GGEMG). Blockade of the α1 adrenergic receptors (α1-AR) or the ionotropic glutamatergic receptors in the pF region decrease the activity of the GGEMG without affecting inspiratory cessation. In contrast, blockade of α2-AR in the pF region extended the duration of GG activity. Notably, the inspiratory and GGEMG activities induced by KF/A7 stimulation were completely blocked by bilateral blockade of glutamatergic receptors in the Bötzinger complex (BötC). While our study found a limited role for α1 and α2 adrenergic receptors at the pF level in modulating the breathing response to KF/A7 stimulation, it became evident that BötC neurons are responsible for the respiratory effects induced by KF/A7 stimulation.

Reappearance of CXCR4 dim/CD5 bright Proliferative Fraction Associates with BTK Mutations and Anticipates Progression in Ibrutinib-Treated CLL

Reciprocal expression of CXCR4 and CD5 on the surface of chronic lymphocytic leukemia (CLL) cells can discriminate the proliferative fraction (CD5high/CXCR4dim, PF), recently egressed from the lymph node, from the resting fraction (CXCR4high/CD5dim, RF) of older, quiescent cells. BTK inhibitors affect the proliferative capacity of CLL cells and cause the redistribution from nodal compartments to the blood stream. Nevertheless, little is known about the impact of long-term treatment of the BTK-inhibitor ibrutinib (IBR) on the PF/RF phenotype. Here, we monitored the PF dynamics in two cohorts of IBR-treated CLL cases with long-term follow-up, and correlated with the emergence of IBR resistance. Longitudinal analysis of the PF under IBR in 31 CLL cases, enrolled in the IOSI-EMA-001 with sequential blood samplings (156 samples, median 6 samples/case) showed a depletion of the PF over time, from 17.7% at pre-treatment to 4.75, 0.4, 1.5, 0.6, 1.5% at later timepoints (0.5, 6, 12, 18, 24 months; p < 0.001, U test), along with loss of proliferative potential by Ki67 expression. We then retrospectively analyzed the PF in 100 IBR-treated CLL cases from the real world, referred for routine immunophenotyping (296 samples, median 3 samples/case). Median PF of pre-IBR samples was 12.0% (range 0.7-50), with a significant drop to 2.7% within one year of treatment and to 1.0% in the second year (p<0.001, U test). 77 cases discontinued IBR due to: toxicity (n=13), progression (n=51), other/death (n=13). Mutations of BTK/ PLCG2 were detected in 30 cases, 28 of which discontinued IBR due to progression and 2 for other/death. To correlate reappearance of the PF with cause of discontinuation, we focused on 64 cases collected within 12 months before/after IBR discontinuation due to toxicity (n=10), progression (n=47) or other/death (n=7), and compared with 22 samples still on treatment for the next 12 months after testing (Panel A). ROC analysis of the PF suggested a criterion of PF>3% as the most discriminating to predict IBR discontinuation due to progression, with a sensitivity of 86.7% and a specificity of 71.1%. This cut-off could separate patients with a longer time-to-progression (median 56 vs. 45 months, p=0.031). 26/47 progressing cases bore BTK/ PLCG2 mutations, with a PF higher than wild-type cases discontinuing for toxicity (8.4% vs. 2.2%; p<0.001) or still on treatment (1.8%, p<0.001). Notably, the 21 BTK/ PLCG2- wild-type progressing cases also showed higher PF compared to cases discontinuing for toxicity (6.9% vs. 2.2%; p<0.001) or still on treatment (1.8%; p<0.001). Notably, PF levels showed no significant correlation with white blood cell counts. Sequential dosages of plasmatic B2M in progressing cases (n=5) revealed steady levels below the 3.5 ug/mL threshold, despite the PF increase (median PF 18%). Cell sorting of the PF/RF fractions from 10 cases showing PF reappearance after prolonged IBR treatment (median 50.7 months) revealed a mean of 1.7 BTK mutations per sample (27 total, range 1-4), a median VAF higher in the PF (23.0%, 0.3-92.3) on average 2.8 times larger than in the RF (5.2%, 0.1-84.8; p=0.003, paired rank test). A similar skewing was present for PLCG2 mutations (median PF VAF: 2.0%, 0.1-6.2; RF VAF: 1.35%, 0.4-2.8; p=0.014). Finally, mRNA-seq was performed in 20 cases, on matching PF/RF fractions both at pre-IBR and progression (9 cases with BTK mutations). Differential expression signature of pre-IBR PF vs. RF, concordant with published gene sets, drove co-clustering of post-IBR PF/RF with their respective counterparts, indicating that PF at progression functionally resembles its pre-treatment counterpart. A strong enrichment of multiple proliferation-related signatures, present in pre-treatment samples, was significantly up-regulated also at progression, independently from BTK mutations (Panel B). In summary, here we report that CLL progression under IBR associates with reappearance of the CD5bright/CXCR4dim PF which precedes clinical progression, increase of serum B2M and WBC counts. Transcriptomic/genetic profiling of the post-IBR PF suggests presence of clonal selection dynamics and active bypass signaling pathways, bona fide taking place within the lymph node microenvironment, including BTK/ PLCG2 mutations. Clinically, longitudinal monitoring of the CXCR4/CD5 fractions by flow cytometry may provide a simple tool helping to intercept CLL progression under IBR therapy.

Saikosaponin-d regulates angiogenesis in idiopathic pulmonary fibrosis through angiopoietin/Tie-2 pathway

ObjectiveIdiopathic pulmonary fibrosis (IPF) is considered as a chronic interstitial lung disease with underlying mechanism of IPF remaining unclear, while there are no definitive treatment options. In recent years, scientists have gradually paid attention to the influence of angiogenesis on IPF. Because IPF is a progressive with microvascular remodeling disorder, scientists have postulated that angiogenesis may also be one of the initiating and contributing factors of the disease. Bupleurum is a common natural Chinese herbal medicine with antibacterial, anti-inflammatory, anti-tumor and other pharmacological effects. As the most important active monomer of Bupleurum, Saikosaponin-d (SSd) is a new discovery with anti-pulmonary fibrosis (PF) activity. This study attempts to investigate the role of SSd in the interference of PF through regulation of angiogenesis in IPF through Angiopoietin (Angpt) /Tie receptor 2 (Tie2) pathway. MethodsRandomly, we allocated C57BL/6 mice into four groups (n = 20 in each group). Afterwards, establishment of IPF model was accomplished via intratracheal administration of bleomycin (BLM, 5 mg/kg), while corresponding drug intervention was given accordingly. On 3rd, 7th, 14th and 28th days after modeling, we performed histopathological examination through staining. Meanwhile, immunohistochemistry (IHC) of PF and the expression of related factors were observed, while Ang/Tie2 pathway was assessed by ELISA with the effect of SSd on angiogenesis related proteins in IPF being explored with IHC and Western Blot technique. ResultsOur results showed that SSd could reduce inflammation and PF levels in lung tissue of experimental mice, while levels of angiogenesis-related factors, namely Tie-2, Ang-1 and ANGPT2 (Ang-2), fibrosis- associated factors like Alpha-smooth muscle actin (α-SMA), collagen-I and hydroxyproline in SSd and dexamethasone (DXM) mice were significantly reduced at each time point compared to BLM (p < 0.01). Additionally, we discovered substantial decreased expressions of Ang-1, Ang-2, Tie-2, α-SMA and collagen-I at protein level in SSd and DXM mice at each time point compared to BLM (p < 0.05). Besides, insignificant differences were observed between SSd and DXM groups (p > 0.05). ConclusionThis study has demonstrated that SSd could down-regulate the expression of ANG-1, Ang-2 and Tie2 in the Ang/Tie2 pathway, and may reduce lung inflammation and PF in BLM-induced mice via inhibition of angiogenesis.

Non-Contact Adaptive Voltage Sensor Based on Electric Field Coupling Principle.

Non-contact voltage sensors based on the principle of electric field coupling have the advantages of simple loading and unloading, high construction safety, and the fact that they are not affected by line insulation. They can accurately measure line voltage without the need to connect to the measured object. Starting from the principle of non-contact voltage measurement, this article abstracts a non-contact voltage measurement model into the principle of capacitive voltage sharing and deduces its transfer relationship. Secondly, it is theoretically inferred that the edge effect of the traditional symmetric structure sensor plate will cause the actual capacitance value between the sensor plates to be greater than the theoretically calculated capacitance value, resulting in a certain measurement error. Therefore, the addition of an equipotential ring structure is proposed to eliminate the edge additional capacitance caused by the edge effect in order to design the sensor structure. In addition, due to the influence of sensor volume, material dielectric constant, and other factors, the capacitance value of the sensor itself is only at pF level, resulting in poor low-frequency performance and imbuing the sensor with a low voltage division ratio. In this regard, this article analyzes the measurement principle of non-contact voltage sensors. By paralleling ceramic capacitors between the two electrode plates of the sensor, the capacitance of the sensor itself is effectively increased, improving the low-frequency performance of the sensor while also increasing the sensor's voltage division ratio. In addition, by introducing a single pole double throw switch to switch parallel capacitors with different capacitance values, the sensor can have different voltage division ratios in different measurement scenarios, giving it a certain degree of adaptability. The final sensor prototype was made, and a high and low voltage experimental platform was built to test the sensor performance. The experimental results showed that the sensor has good linearity and high measurement accuracy, with a ratio error of within ±3%.

Solid-State Fermentation as Green Technology to Improve the Use of Plant Feedstuffs as Ingredients in Diets for European Sea Bass (Dicentrarchus labrax) Juveniles.

This study aimed to evaluate the utilization by juvenile European sea bass of a SSFed PF mixture with Aspergillus niger CECT 2088. A 22-day digestibility and a 50-day growth trial were performed testing four diets, including 20 or 40% of an unfermented or SSFed PF mixture (rapeseed, soybean, rice bran, and sunflower seed meals, 25% each). SSF of the PF added cellulase and β-glucosidase activity to the diets. Mycotoxin contamination was not detected in any of the experimental diets except for residual levels of zearalenone and deoxynivalenol (100 and 600 times lower than that established by the European Commission Recommendation-2006/576/EC). In diets including 20% PF, SSF did not affect growth but increased apparent digestibility coefficients of protein and energy, feed efficiency, and protein efficiency ratio. On the contrary, in diets including 40% PF, SSF decreased growth performance, feed intake, feed and protein efficiency, and diet digestibility. SSF decreased the intestinal amylase activity in the 40% SSFed diet, while total alkaline proteases decreased in the 20% and 40% SSFed diets. Hepatic amino acid catabolic enzyme activity was not modulated by SSF, and plasma total protein, cholesterol, and triglyceride levels were similar among dietary treatments. In conclusion, dietary inclusion of moderate levels of the SSFed PF, up to 20%, improves the overall feed utilization efficiency without negatively impacting European sea bass growth performance. The replacement of PF with the SSFed PF mixture may contribute to reducing the environmental footprint of aquaculture production.

Weak Capacitance Detection Circuit of Micro-Hemispherical Gyroscope Based on Common-Mode Feedback Fusion Modulation and Demodulation.

As an effective capacitance signal produced by a micro-hemisphere gyro is usually below the pF level, and the capacitance reading process is susceptible to parasitic capacitance and environmental noise, it is highly difficult to acquire an effective capacitance signal. Reducing and suppressing noise in the gyro capacitance detection circuit is a key means to improve the performance of detecting the weak capacitance generated by MEMS gyros. In this paper, we propose a novel capacitance detection circuit, where three different means are utilized to achieve noise reduction. Firstly, the input common-mode feedback is applied to the circuit to solve the input common-mode voltage drift caused by both parasitic capacitance and gain capacitance. Secondly, a low-noise, high-gain amplifier is used to reduce the equivalent input noise. Thirdly, the modulator-demodulator and filter are introduced to the proposed circuit to effectively mitigate the side effects of noise; thus, the accuracy of capacitance detection can be further improved. The experimental results show that with the input voltage of 6 V, the newly designed circuit produces an output dynamic range of 102 dB and the output voltage noise of 5.69 nV/√Hz, achieving a sensitivity of 12.53 V/pF.

Endogenous maternal serum preimplantation factor levels in earlyonset preeclamptic pregnancies

Objective: Preimplantation-factor (PIF) is a new peptide with many potential functions. We aimed to compare the maternal serum PIF levels among early-onset preeclamptic patients with the healthy controls at the same gestational age. Patients and Methods: Thirty-nine early-onset preeclamptic (&amp;lt; 34 gestational weeks) patients and 45 healthy expecting women have been added to our study. Patients with or suspicion of any chronical maternal disease, gestational diabetes, twin pregnancies, fetal or placental anomalies or any other obstetric complications have been excluded. Competitive enzyme-linked immunosorbent assay (ELISA) (Elabscience Biotechnology Co., Texas, USA) has been used to analyze the PIF levels in the collected samples. Gestational age, maternal age, gravida, parity, fetal growth, body mass index (BMI), maternal weight and height, plasma PIF levels have been collected/measured and analyzed in both groups. Results: The primary outcome of our study –the Preimplantation Factor- was significantly higher in study group than the healthy controls (100.36 ± 41.92 vs. 83.14 ± 51.27 p=0.016). Conclusions: We have found the PF levels statistically higher in the study group. PIF levels might have a role in the progression and pathogenesis of the preeclamptic patients. Further studies with larger groups have to be planned and performed to resolve the real relation between PIF and preeclampsia.

A Method to Electrically Compensate Close Approach Effect for Calculable Capacitor

Calculable capacitor (CC) is outstanding in its linear relationship between capacitance and its guard electrodes’ displacement. However, the relationship is no longer linear for capacitance below 0.1 pF level because the electrostatic field on guard electrode’s tip gets disordered, which is known as close approach effect. To rescue the linearity, we assemble an auxiliary electrode on the end of the movable guard electrode and load a scaled ac voltage with the same frequency as capacitance bridge by a ratio transformer to make the electrostatic field regular. The scaled ratio is carefully selected by simulation and experiments. We show that some specified ratios can perfectly compensate the close approach effect. As a result, the range of the linearity of the capacitance–distance curve is extended by 10 mm on our prototype by adopting optimal positive compensation voltage. Furthermore, the nonlinearity can be totally compensated even with capacitance less than 100 aF when adopting negative compensation voltage.

Prevalence of Chronic Kidney Disease of Uncertain Etiology Within Selected Farming Communities in Rural Sri Lanka.

Chronic kidney disease of uncertain etiology (CKDu) is an emergent health concern, particularly in tropical farming communities in several global hotspots, including Sri Lanka. This particular nephropathy is characterized by a progressive decline in kidney function in the absence of conventional chronic kidney disease (CKD) risk factors such as diabetes mellitus, hypertension, and other identifiable kidney disorders. As it is almost asymptomatic at early stages, CKDu is mostly diagnosed at late stages with significant kidney damage. Hence, the identification of disease susceptibility and vulnerable communities at the earliest possible instances is highly important for the management of the disease. We aimed to compare kidney health across three different farming communities in Sri Lanka to identify CKDu susceptibilities. A cross-sectional study was performed with three selected farming communities: paddy farmers (PF; N = 581), sugarcane farmers (SF; N = 550), and vegetable farmers (VF; N = 244) in comparison with an age-matched control group of nonfarming (NF; N = 225) individuals. A medical examination was performed to investigate health status and medical history, whereas a urinalysis was performed to determine creatinine and albumin contents. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) were used for assessment of kidney function. CKDu susceptibility was determined based on eGFR, and urinary ACR adhering to the clinical practice guidelines in Sri Lanka. The median (interquartile range [IQR]) eGFR levels of PF (85 mL/min/1.73 m2 [72-97]) and SF (93 mL/min/1.73 m2 [73-112]) were significantly lower than that of the NF group (103 mL/min/1.73 m2 [87-125]) (P < .0001), whereas eGFR of VF (100 mL/min/1.73 m2 [80-111]) was not significantly different compared with NF. The median (IQR) urinary ACR levels of the study groups, PF, SF, VF, and NF, were 0.59 (0.26-1.45), 0.46 (0.28-0.88), 0.45 (0.34-0.90), and 0.44 (0.34-1.02) mg/mmol, respectively. However, urinary ACR did not differ significantly across the study groups (P > .05). The prevalence of CKDu within PF (13.60%), SF (12.54%), and VF (6.67%) communities was significantly higher (P < .05) compared with the NF (2.67%). Of the total CKD cases, CKDu susceptible cases represented 73%, 69%, 50%, and 25% in PF, SF, VF, and NF, respectively, indicating a high risk of CKDu susceptibility among farming communities. Moreover, a noteworthy association of CKDu was observed with agrochemical exposure (odds ratio [OR] = 3.11, 95% confidence interval [CI] = 1.36-7.09). Concerning the farming practices, sugarcane farming showed the highest association with CKDu prevalence (OR = 3.40, 95% CI = 1.49-7.78). Compared with the nonfarming group, a significant risk of CKDu was observed in the three farming communities, particularly among paddy and sugarcane farmers. Longitudinal epidemiological studies to identify vulnerable farming communities and associated risk factors are critically needed to develop effective management strategies against CKDu within farming communities.

Soil water balance and wettability methods in soil treated with biochar and/or compost

The impacts of biochar application in combination with compost on soil hydrological conditions such as infiltration, water-storage capacity, and methods of soil wettability, are not well understood. The aim of this study was to fill this knowledge gap and propose the best composition proportion of compost and/or biochar to improve sand soil water balance. For this purpose, we examined three different mixtures of sand and compost and six different mixtures of sand, compost, and biochar with respect to their wettability and water infiltration using tree methods, (I) Water Droplet Penetration Time Test (WDPT test), (II) Wilhelmy Plate Method (WPM) and (III) Capillary Rise Method (CRM) applied at different soil water potential (pF) levels. The different mixtures were characterized by texture, bulk density, field capacity, and soil water holding capacity through measurement of the water content of soil columns. Increasing biochar plus compost or compost alone had contributed to increasing the soil water holding capacity and water available content. The best composition with the highest water storage capacity, plant-available water, and wettability was: 0.6% of biochar, 5.4% soil organic matter (SOM), and 93.99% of sand. According to the WDPT test, the increased content of biochar contributed to improving the soil wettability, this test was preferred since 1) WDPT appeared to allow the best estimates of wetting behavior of the different mixtures, 2) the column samples were the least disturbed, and 3) the test was particularly feasible at different water content levels. However, WDPT was strongly dependent on the conductor of the experiment and the accurate measurement of short infiltration times (0s - 2s) proved challenging. The WDPT results indicate that biochar might enhance the infiltration capacity under natural conditions and the combined results indicate that biochar-compost-applications are not expected to cause ecologically critical hydrophobicity or a critical lowering of the sandy soil infiltration capacity.Graphical abstract

Two-Mask Wafer-Level Vacuum Packaging With Bulk-Si 3D Interconnects for MEMS Devices and Its Package Performances

We present the novel 3D wafer-level vacuum packaging technology for MEMS, which only needs two masks and is realized by Au-Si eutectic bonding with a low-resistivity Si Cap wafer. Wherein, Au-Si bonding pads and rings are formed to accomplish vertical interconnects and a vacuum package respectively. Applied to resonators with two typical substrate wafers of Si and Glass, this 3D package structure has further gone through the systemic characterizations. Specifically, the high-reliable mechanic strengths of device packages are revealed from Au-Si bonding strengths measured as about 20 MPa in tensile tests. Based on analyzing parasitic capacitance networks in device packages, the feed-through effect in resonance tests can be effectively relieved by grounding on each Si layer in device package structures (i.e. the parasitic capacitance reduced from the level of pF to fF). By resonance tests, it is found that increasing the degassing duration (30 min <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 60$ </tex-math></inline-formula> min <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 100$ </tex-math></inline-formula> min) is beneficial for improving package vacuum degrees as well as consistencies (69% within 4–30 kPa <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 88$ </tex-math></inline-formula> % within 0.6-1.2 kPa <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 85$ </tex-math></inline-formula> % within 0.6-0.8 kPa), and hermetic package yields (73% <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 86$ </tex-math></inline-formula> % <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\to 100$ </tex-math></inline-formula> %). Besides, device packages are verified to have good long-term stability by monitoring quality factor variations in 6 months. Overall, this proposed 3D packaging technology has extensive application prospects in various MEMS devices due to its inherently-simple process, low capacitive feed-through effect, and fine package performances. Also, test results provide instructions on the realization of low-parasitic-capacitance signal interfaces and the optimization of wafer-level vacuum package processes.

Histamine/H1 receptor signaling in the parafacial region increases activity of chemosensitive neurons and respiratory activity in rats.

Histaminergic neurons of the tuberomammillary nucleus (TMN) are pH sensitive and contribute to CO2/H+-dependent behaviors including arousal and respiratory activity. TMN neurons project to several respiratory centers including the ventral parafacial region (pF), where the chemosensitive retrotrapezoid (RTN) neurons are located, and since RTN neurons are an important source of CO2/H+-dependent respiratory drive, we wondered whether histamine contributes to RTN chemoreception. To test this, we characterized effects of histamine on mean arterial pressure (MAP) and diaphragm muscle activity (DIAEMG) in urethane-anesthetized, vagotomized, and artificially ventilated male Wistar rats. Unilateral injection of histamine in the pF (25 mM) increased DIAEMG amplitude without changing DIAEMG frequency and MAP. Bilateral injections of the H1 receptor antagonist diphenhydramine hydrochloride (DPH; 0.5 mM) into the pF decreased baseline DIAEMG amplitude and frequency and MAP. Despite the strong inhibitory effect of DPH on baseline breathing, the hypercapnic ventilatory response was preserved under these experimental conditions. At the cellular level, chemosensitive RTN neurons showed a dose-dependent excitatory response to histamine that was blunted by DPH and mimicked by H1 receptor agonist 2-pyridylethylamine dihydrochloride (2PYEA) both under control conditions and when fast neurotransmitter receptors were blocked. We also tested effects of 2PYEA in the presence of serotonin, another wake-on neurotransmitter that activates RTN chemoreceptors partly by activation of Gq-coupled receptors. We found that the response to 2PYEA was diminished in serotonin, suggesting that RTN neurons have a limited capacity to respond to multiple Gq-coupled modulators. These results suggest that histamine can modulate breathing at the pF level by a mechanism involving H1 receptors.NEW & NOTEWORTHY Histamine/H1 receptor signaling activates retrotrapezoid (RTN) neurons under control conditions and to a lesser extent in the presence of serotonin. These results suggest that RTN neurons have a limited capacity to respond to simultaneous activation of multiple Gq-coupled receptors.

The Production of Dual-Purpose Triticale in Arid Regions: Application of Organic and Inorganic Treatments under Water Deficit Conditions

Most of the arid and semi-arid regions, particularly in the Mediterranean area, suffer from the lack of a sufficient quantity of high-quality feed, as well as a low amount of rainfall that is unevenly distributed, resulting in the region being highly vulnerable to drought. A field experiment was carried out at the experimental station of the Faculty of Desert and Environmental Agriculture, Fuka, Matrouh University, Egypt during the winter seasons of 2018/19 and 2019/20 to study the performance of triticale (X Triticosecale Wittmack), grown under water deficit conditions, in terms of productivity and quality. The study investigated the influence of five levels of potassium fertilization (PF; 0, 43.2, 86.4, 129.6, and 172.8 kg ha−1) and ascorbic acid (AA; 0, 25, 50, 75, and 100 mg L−1) that was applied to the triticale grains before sowing and humic acid (HA; 0, 2.4, 4.8, 7.2, and 9.6 kg ha−1) that was applied as powder to the soil 21 days after sowing followed by sprinkler irrigation on triticale forage and grain production when forage was removed at variable ages at cutting (AC), determined as days after sowing (AC; 40, 65, 90, 115, and 140 DAS) on forage yield and nutritive value, in addition to the final grain yield of triticale. The experimental design was a central composite design with one replicate. Results indicated that the PF*AC interaction was significant, and it gave values of 84.78 and 238.00 g kg−1 for crude protein (CP) and degraded neutral detergent fiber (DNDF). In addition, the interaction between AA and AC was significant for CP, acid detergent fiber (ADF), 100-grain weight (100 GW), number of spikes m−2 (NSM−2), and plant height (PH). Moreover, the AC*HA interaction was significant with values of 175.17 and 247.00 g kg−1 for CP and DNDF, respectively, and 0.55 t ha−1 for grain yield (GY). Age at cutting exerted the strongest effect on the studied characteristics. It was observed that the contents of neutral detergent fiber (NDF), ADF, acid detergent lignin (ADL), and non-fiber carbohydrates (NFC) in the triticale forage significantly increased when the crop was cut at an advanced age, unlike CP, DNDF, GY, NSM−2, 100 GW, and PH that decreased with advanced AC. The highest values of 271.00, 256.00, and 268.00 g kg−1 for DNDF were obtained with higher levels of either PF, AA, or HA, respectively. However, the highest value of GY (0.97 t ha−1) was obtained with higher levels of PF*HA averaged over the two seasons. The interaction between AA*HA resulted in 393.39, 311.00, 27.13 g kg−1, and 0.94 t ha−1, for NDF, DNDF, ADL, and GY, respectively. The highest significant NDF (413.11 g kg−1) and DNDF (307.50 g ka−1) values were obtained with the application of high levels of either AA or HA. In the dual-purpose production system, it is recommended to cut the triticale crop at 65 DAS to achieve the optimum balance between forage yield and quality on the one hand, and final grain yield on the other hand. In the arid regions, application of PF, AA, and HA could help in reducing the damage caused by water deficit.

Differentiation and correlation of spatial pattern and multifunction in rural settlements considering topographic gradients: Evidence from Loess Hilly Region, China

In the process of rapid industrialization and urbanization, China's rural settlements are undergoing rapid differentiation and reorganization. Their spatial pattern and multifunction have attracted much attention. In the Loess Hilly Region of China, topographic factors are deeply involved in the formation and evolution of the spatial pattern and multifunction in rural settlements. Therefore, this paper proposed a new method of topographic gradient analysis based on micro-geomorphic units. Taking Tianshui City in Longzhong Loess Hilly Region as an example, we analyzed the gradient differentiation and spatial correlation of the spatial pattern and multifunction in rural settlements. The results indicated that: (1) The topographic gradient differentiation of spatial pattern in rural settlements was distinct. As the topographic gradients rose, the numerical distributions of TA, AREA_CV, MPI, PR, and SHDI were generally concentrated from high to low values. The numerical distribution of LFI was generally scattered from low to high values. In addition, the numerical distribution of AWMSI and AWMPFD showed the “arch bridge” pattern. (2) The topographic gradient differentiation of multifunction in rural settlements was distinct. The overall level of LF was relatively low, and the numerical difference was small. It had the characteristics of concentrated distribution and marginal distribution in geographical space. The overall level of PF was low, and the spatial distribution had strong urban directivity and significant topographic gradient differences. The overall level of EF was relatively low, and the spatial distribution had significant horizontal zonality and topographic gradient differences. (3) Rural settlements' scale, distribution, and structure were generally synergistic with LF and PF, but there were trade-off relationships with EF. Moreover, the trade-off/synergy relationships between spatial pattern and multifunction had significant spatial heterogeneity in terms of spatial distribution. This paper is significant for formulating settlement development and construction plans, guiding spatial reconstruction and functional reorganization, improving settlement living environment, and promoting rural revitalization.

Level of Physical Activity and Its Relationship to Self-Perceived Physical Fitness in Peruvian Adolescents.

Background: Physical activity and physical fitness play an important role in adolescence. Both are considered to be indicators of the current and future health status of young adults. The main objective of this article was to report the normative values of the Physical Activity Questionnaire for Adolescents (PAQ-A) and the International Fitness Scale (IFIS) instruments in Peruvian school adolescents. Methods: A sample of 1229 participants (622 girls and 607 boys) aged between 12 and 17 years was used. The type of study was descriptive-comparative. All measures used were obtained by means of self-administered instruments. The PAQ-A was used to assess the level of physical activity and the IFIS to assess the self-perceived physical fitness level of the adolescents. Results: It was observed that the PAQ-A questionnaire results obtained from the total sample was 2.34; significantly higher for boys (2.41) compared with girls (2.27). For the IFIS, the total score was 3.07, with boys obtaining 3.13 and girls 2.97. Conclusions: It was concluded that there was a direct relationship between the level of PA and self-perceived PF in Peruvian adolescents. Furthermore, adolescent boys were more physically active than girls and they had a better self-perceived PF with the exception of flexibility. Finally, there was a higher weight category involved at the lower level of PA.

Fine root biomass stocks but not the production and turnover rates vary with the age of tropical successional forests in Southern Mexico

Fine root production, turnover, and decomposition are fundamental rhizosphere processes that can vary when young forest ecosystems pass through different phases of succession towards maturity. To assess these changes during succession, we applied ingrowth bag and sequential coring methods for fine root production and a modified negative exponential model for fine root decomposition at four phases of tropical forest chronosequence: 1) young secondary forests of about 8 years, 2) medium secondary forests of 15 years, 3) advanced secondary forests of 25 years, and 4) old-growth primary forests of >100 years. Primary forests stored higher fine root biomass than secondary forests but the average fine root productivity did not differ statistically between successional phases. Fine root turnover rates were >1 yr−1 for all the phases of succession, indicating that the turnover was higher than the standing fine root biomass. Fine root decay models showed that the decomposition rates did not differ significantly between successional phases. Furthermore, fine root production and mortality correlated positively to soil organic carbon concentrations. Our results showed that fine root productivity and turnover rates in secondary forests get to PF level from the younger phases of succession. The results have important implications in understanding the successional patterns regarding belowground resource allocation, nutrient turnover, and soil organic carbon sequestration in the constantly changing tropical forests ecosystems.

Molecular characterization, expression analysis and function identification of Pf_TNF-α and its two receptors Pf_TNFR1 and Pf_TNFR2 in yellow catfish (Pelteobagrus fulvidraco)

Inflammation is a common manifestation of body immunity and mediates a cascade of cytokines. Tumor necrosis factor-α (TNF-α), as a multi-effect cytokine, plays an important role in the inflammatory response by interacting with its receptor (TNFR). In this study, Pf_TNF-α, Pf_TNFR1 and Pf_TNFR2 genes were cloned from yellow catfish (Pelteobagrus fulvidraco), and bioinformatics analyses showed that the three genes were conserved and possessed similar sequence characteristics as those of other vertebrates. The qPCR results showed that Pf_TNF-α, Pf_TNFR1 and Pf_TNFR2 mRNAs were constitutively expressed in 14 tissues and the lymphocytes of four tissues from healthy adults. The mRNA expression levels of Pf_TNF-α and Pf_TNFR1 genes were significantly up-regulated in the spleen, liver, trunk kidney, head kidney and gill after Edwardsiella ictaluri infection, while the mRNA expression of Pf_TNFR2 was significantly up-regulated in the spleen, and down-regulated in the liver and gill. In the isolated peripheral blood leukocytes (PBLs) of yellow catfish, the expression of Pf_TNF-α mRNA was notably up-regulated and the two Pf_TNFR transcripts were distinctly down-regulated after stimulation with lipopolysaccharides (LPS), peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly I:C) and phytohaemagglutinin (PHA). After stimulated by recombinant (r) Pf_sTNF protein, the mRNA expressions of various inflammatory factors genes were up-regulated in the PBLs. Meanwhile, rPf_sTNF promoted the phagocytic activity of leukocytes, whereas the activity mediated by rPf_sTNF could be inhibited by rPf_TNFR1CRD2/3 and rPf_TNFR2CRD2/3. The up-regulation of TNF-α and IL-1β mRNAs expression triggered by rPf_sTNF could be inhibited by MAPK inhibitor (VX-702) and NF-κB inhibitor (PDTC). rPf_sTNF induced the expression of FADD mRNA in PBLs and increased the apoptotic rate of PBLs, and inhibiting the NF-κB and MAPK signal pathways could enhance the apoptosis of PBLs. The results indicate that Pf_TNF-α, Pf_TNFR1 and Pf_TNFR2 play important roles in the immune response of yellow catfish to bacterial invasion.

Water Retention and Saturation Degree of Peat Soil in Sebangau Catchment Area, Central Kalimantan

Water is an essential factor in forming, utilization, management, and sustainability of peat soil. This study was to obtain characteristics of water retention and porosity of peat soil. Peat samples were taken from the Natural Laboratory of Peat Forest, Central Kalimantan at shallow, medium, and deep peat at 0-50cm (surface) and 50-100 cm (subsurface), while laboratory analyses carried out at Soil Laboratory, Universitas Gajahmada. The result shows that volumetric moisture content at the surface lower than subsurface, except for deep peat. The total pore for the surface was 84.67-86.98%, while subsurface layers were 83.53-86.93%. For surface layer, saturated degree (S) medium peat higher than shallow and deep peat, while for shallow subsurface peat higher than medium and deep peat. S value all pF levels of surface for medium and deep peat higher than the subsurface. Bulk density for surface was 0.094g.cm-3 (rb(wet)) and 0.22g.cm-3(rb (dry)) for shallow peat while medium peat are 0.084–0.087g.cm-3(rb(wet)) and 0.18–0.20g.cm-3(rb(dry)), deep peat 0.064–0.090g.cm-3(rb(wet)) and 0.11–0.16g.cm-3(rb(dry)). For subsurface, bulk density of medium peat are 0.094–0.107g.cm-3 (rb(wet)) and 0.16–0.20g.cm-3 (rb(dry)), deep peat are 0.067–0.090g.cm-3 (rb(wet)) and 0.10–0.17g.cm-3 (rb(wet)). The particle density of surface and subsurface for shallow peat higher than medium and deep peat, with values 0.67-0.77g.cm3, 0.61-0.66g.cm3, and 0.53-0.63g.cm3 for shallow, medium, and deep peat, respectively. Total pores for the surface layer decrease with increasing dry bulk density (R = 0.624) and particle density (R = 0.375). This fact seems to confirm a directly proportional relationship between parameters bulk and particle density with total pores.

Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease.

Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. To develop a novel method to quantify cerebrospinal fluid (CSF) levels of α-synuclein protofibrils (α-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer's disease (AD, tau<350 pg/mL, amyloid-beta 42 (Aβ42)>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total α-synuclein (α-syn) levels were analyzed with a commercial ELISA-kit. The assay is specific to α-syn PF, with no cross-reactivity to monomeric α-syn, or the β- and γ-synuclein variants. CSF α-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using α-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total α-syn were significantly different between the PD and CBD groups (p = 0.04). The developed method specifically quantifies α-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.