Hydrographic proxies for submarine groundwater discharge in the Jiulong River estuary and global perspectives.

Submarine groundwater discharge (SGD) significantly impacts most coastal waters. However, its quantification, depending on chemical tracers/proxies, limits its parameterization in numerical models. This study explored the hydrographic proxies of SGD in the Jiulong River estuary (JRE) using 226Ra and 228Ra as SGD tracers. Our results showed significant monthly fluctuations in the flux of SGD, with a peak in June and a minimum in April. On average, the flux of SGD was equivalent to 10 ± 1.67 % of the concurrent river discharge, with the area-normalized rate of 0.007 ± 0.017 to 0.13 ± 0.04 m/day. Positive SGD response to river discharge implies a connection with the surface runoff of the shallow aquifers. Furthermore, the flux of SGD presented a significant negative correlation with the return flow factor and flushing time of the estuary. The radium activities in the estuary were positively correlated with water depth, indicating that SGD was not driven by tidal pumping. Instead, physical mixing in low to middle salinity regions predominated such behavior of radium. Our results indicate that river discharge, flushing time and return flow factor may serve as hydrographic proxies of SGD in the JRE and potentially be applicable in parameterization of SGD in numerical models in similar coastal ecosystems. Globally, a positive correlation between SGD flux and river discharge emphasizes the latter as a general proxy in estuaries.

Identification of VRK1 as a Novel Potential Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma.

Background: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC). Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression. Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism. Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.

An Autoregressive-Based Kalman Filter Approach for Daily PM2.5 Concentration Forecasting in Beijing, China.

With the acceleration of urbanization, air pollution, especially PM2.5, has seriously affected human health and reduced people's life quality. Accurate PM2.5 prediction is significant for environmental protection authorities to take actions and develop prevention countermeasures. In this article, an adapted Kalman filter (KF) approach is presented to remove the nonlinearity and stochastic uncertainty of time series, suffered by the autoregressive integrated moving average (ARIMA) model. To further improve the accuracy of PM2.5 forecasting, a hybrid model is proposed by introducing an autoregressive (AR) model, where the AR part is used to determine the state-space equation, whereas the KF part is used for state estimation on PM2.5 concentration series. A modified artificial neural network (ANN), called AR-ANN is introduced to compare with the AR-KF model. According to the results, the AR-KF model outperforms the AR-ANN model and the original ARIMA model on the predication accuracy; that is, the AR-ANN obtains 10.85 and 15.45 of mean absolute error and root mean square error, respectively, whereas the ARIMA gains 30.58 and 29.39 on the corresponding metrics. It, therefore, proves that the presented AR-KF model can be adopted for air pollutant concentration prediction.

Pan-genome analysis highlights the role of structural variation in the evolution and environmental adaptation of Asian honeybees.

The Asian honeybee, Apis cerana, is an ecologically and economically important pollinator. Mapping its genetic variation is key to understanding population-level health, histories and potential capacities to respond to environmental changes. However, most efforts to date were focused on single nucleotide polymorphisms (SNPs) based on a single reference genome, thereby ignoring larger scale genomic variation. We employed long-read sequencing technologies to generate a chromosome-scale reference genome for the ancestral group of A. cerana. Integrating this with 525 resequencing data sets, we constructed the first pan-genome of A. cerana, encompassing almost the entire gene content. We found that 31.32% of genes in the pan-genome were variably present across populations, providing a broad gene pool for environmental adaptation. We identified and characterized structural variations (SVs) and found that they were not closely linked with SNP distributions; however, the formation of SVs was closely associated with transposable elements. Furthermore, phylogenetic analysis using SVs revealed a novel A. cerana ecological group not recoverable from the SNP data. Performing environmental association analysis identified a total of 44 SVs likely to be associated with environmental adaptation. Verification and analysis of one of these, a 330 bp deletion in the Atpalpha gene, indicated that this SV may promote the cold adaptation of A. cerana by altering gene expression. Taken together, our study demonstrates the feasibility and utility of applying pan-genome approaches to map and explore genetic feature variations of honeybee populations, and in particular to examine the role of SVs in the evolution and environmental adaptation of A. cerana.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinib in vitro and in vivo.

Introduction: Chronic lymphocytic leukemia (CLL) is characterized by an aberrant cytokine network that can support tumor growth by triggering janus kinase (JAK)/STAT pathways. Targeting cytokine-signaling should then be a rational therapeutic strategy but the JAK inhibitor ruxolitinib failed to control and seemingly accelerated the disease in clinical trials. Methods: The effect of ruxolitinib on primary human CLL cells was studied in vitro and in vivo. Results: Ruxolitinib increased phosphorylation of IRAK4, an important toll-like receptor (TLR)- signaling intermediate, in circulating CLL cells in vitro. It also enhanced p38 and NFKB1 phosphorylation while lowering STAT3 phosphorylation in CLL cells activated with TLR-7/8 agonists and IL-2. Among the cytokines made by activated CLL cells, high levels of IL-10 contributed strongly to STAT3 phosphorylation and inhibited TLR7 activity. Ruxolitinib limited TLR-mediated IL10 transcription and markedly reduced IL-10 production in vitro. It also decreased blood levels of IL-10 while increasing TNFα along with phospho-p38 expression and gene sets associated with TLR-activation in CLL cells in vivo. The bruton's tyrosine kinase inhibitor ibrutinib decreased IL-10 production in vitro but, in contrast to ruxolitinib, blocked initial IL10 transcription induced by TLR-signaling in vitro, decreased TNFα production, and deactivates CLL cells in vivo. Discussion: These findings suggest the possible benefits of inhibiting growth factors with JAK inhibitors in CLL are outweighed by negative effects on potential tumor suppressors such as IL-10 that allow unrestrained activation of NFκB by drivers such as TLRs. Specific inhibition of growth-promoting cytokines with blocking antibodies or infusing suppressive cytokines like IL-10 might be better strategies to manipulate cytokines in CLL.

Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study.

BACKGROUND: Opioid-reduced anesthesia may accelerate postoperative rehabilitation by reducing opioid-related side effects. The objective was to investigate the feasibility of opioid-reduced general anesthesia based on esketamine and to observe postoperative nausea and vomiting (PONV), postoperative pain, hemodynamics and other adverse reactions in gynecological day surgery compared with the traditional opioid-based anesthesia program. METHOD: This study was conducted as a prospective parallel-group randomized controlled trial. A total of 141 adult women undergoing gynecological day surgery were included. Patients were randomly assigned to receive traditional opioid-based anesthesia (Group C) with alfentanil, or opioid-reduced anesthesia (a moderate-opioid group (Group MO) and low-opioid group (Group LO) with esketamine and alfentanil). For anesthesia induction, the three groups received 20, 20, 10 µg/kg alfentanil respectively and Group LO received an additional 0.2 mg/kg esketamine. For maintenance of anesthesia, the patients in Group C received 40 µg/kg/h alfentanil, and those in Group MO and Group LO received 0.5 mg/kg/h esketamine. RESULTS: Patients in the three groups had comparable clinical and surgical data. A total of 33.3% of patients in Group C, 18.4% of patients in Group MO and 43.2% of patients in Group LO met the primary endpoint (p = 0.033), and the incidence of nausea within 24 hours after surgery in Group MO was lower than in Group LO (p < 0.05). The extubation time, median length of stay in the hospital after surgery and visual analog scale (VAS) of postoperative pain were equivalent in the three groups. The frequencies of adverse hemodynamic events in the MO 1(0, 2) and LO 0(0, 1) groups were significantly decreased (p < 0.05). Compared with Group C, the median length of stay in the postanesthesia care unit (PACU) in Group LO was increased, 60.0 (36.25, 88.75) vs. 42.5 (25, 73.75) minutes (p < 0.05). CONCLUSIONS: Opioid-reduced anesthesia based on esketamine is feasible and provides effective analgesia for patients. Esketamine provided a positive analgesic effect and the opioid-reduced groups showed more stable hemodynamics. However, less or no use of opioids did not result in a more comfortable prognosis. TRIAL REGISTRATION: This study was registered at Chictr.org.cn (NO. ChiCTR2100053153 ); November 13, 2021.

Enhanced IFN Sensing by Aggressive Chronic Lymphocytic Leukemia Cells.

Type I IFN is made by cells in response to stress. Cancer cells exist in a state of stress, but their IFN response is complex and not completely understood. This study investigated the role of autocrine IFN in human chronic lymphocytic leukemia (CLL) cells. CLL cells were found to make low amounts of IFN via TANK-binding kinase 1 pathways, but p-STAT1 and -STAT2 proteins along with IFN-stimulated genes that reflect IFN activation were variably downregulated in cultured CLL cells by the neutralizing IFNAR1 Ab anifrolumab. Patients with CLL were segregated into two groups based on the response of their leukemia cells to anifrolumab. Samples associated with more aggressive clinical behavior indicated by unmutated IGHV genes along with high CD38 and p-Bruton's tyrosine kinase expression exhibited responses to low amounts of IFN that were blocked by anifrolumab. Samples with more indolent behavior were unaffected by anifrolumab. Hypersensitivity to IFN was associated with higher expression of IFNAR1, MX1, STAT1, and STAT2 proteins and lower activity of negative regulatory tyrosine phosphatases. Autocrine IFN protected responsive CLL cells from stressful tissue culture environments and therapeutic drugs such as ibrutinib and venetoclax in vitro, in part by upregulating Mcl-1 expression. These findings suggest hypersensitivity to IFN may promote aggressive clinical behavior. Specific blockade of IFN signaling may improve outcomes for patients with CLL with higher-risk disease.

The prediction model for haze pollution based on stacking framework and feature extraction of time series images.

In this paper, we propose a new model called "image-feature-stacking prediction model" to study the prediction problem of univariate time series data. Its main idea is to convert univariate time series data into corresponding images, and then use the optimized Inception-v1 network to extract hidden features from the images as input variables, based on these features, a two-layer stacking ensemble learning framework is constructed to output the final predicted values. The main contribution of the newly proposed model is to convert one-dimensional time series data into two-dimensional images, and automatically extract features from images. This method can truly mine the intrinsic relationship between the data instead of simply relying on descriptive statistical features to replace the original time series, thereby improving the prediction performance of the model. We use the new prediction model to predict daily PM2.5 concentration, for one-step prediction, the results show that compared with the other three time series prediction models, the proposed prediction model reduces the mean absolute percentage error and mean absolute scaled error to 19.204% and 1.242, respectively, which is 76.607% and 77.004% lower than the maximum value of mean absolute percentage error and mean absolute scaled error of four prediction models. We also make two-step and three-step predictions, and the newly proposed model also shows encouraging performance.

The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway.

The pathogenesis of sepsis-associated encephalopathy (SAE) involves many aspects, including intracellular peroxidative stress damage, mitochondrial dysfunction, and cell apoptosis. In this study, we mainly explored the influence of P2X7R on the cognitive function of SAE and its molecular mechanism. We established a sepsis model using lipopolysaccharide (LPS) stimulation, followed by an assessment of cognitive function using Morris water maze, and then Western Blot was used to analyze the expression of tight junction proteins ZO-1 and Occludin in the hippocampus of mice. TUNEL assay was used to analyze the apoptosis of brain cells in frozen brain slices of mice during sepsis. Human brain microvascular endothelial cells (HBMECs) were used to research the molecular mechanism of brain cell damage induced by P2X7R. The results showed that P2X7R inhibitors dramatically improved the survival rate of mice, relieved the cognitive dysfunction caused by LPS stimulation, and significantly reduced the brain cell apoptosis caused by LPS. In addition, the inhibition of P2X7R can also reduce the production and accumulation of reactive oxygen species (ROS) in HBMECs in vitro and inhibit the apoptosis signaling pathway associated with mitochondrial serine protease Omi/HtrA2 in HBMECs in vitro. These results suggest that P2X7R has strong value as a potential target for the treatment of SAE.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates II-The personalized analysis of partial pressure of oxygen and carbon dioxide difference between umbilical artery and vein at same time in same newborn].

Objective: In order to explore the mechanism of neonatal spontaneous breathing, the difference of oxygen and carbon dioxide between umbilical cord arteries and veins before the start of spontaneous breathing after birth has been analyzed among people. In this part, the related information is analyzed individually. Methods: After all fetal parents signed the informed consent before birth, and before the newborn was born and did not breathe, the umbilical cord was exposed as quickly as possible, and the heparinized arterial indwelling needle was inserted into the umbilical artery and umbilical vein in the direction of newborn and placenta, and then blood was taken continuously. Although dozens of mothers were selected,but only 3 cases were collected from Pua and Puv blood samplers at the same time for blood gas analysis and determination, and the differences and dynamic changes of umbilical vein and umbilical artery were calculated and analyzed. Results: In all 3 none spontaneous breathing newborns,PuvO2 was significantly higher than PuaO2 at the same time (P<0.01), with an average difference of (24.17±7.09) mmHg; while PuvCO2 was significantly lower than PuaCO2 (all P<0.01), with an average difference of (-7.67±3.70) mmHg.The difference of Puv-uaO2 was significantly higher than those of Puv-uaCO2 (P<0.05). Conclusion: PuaO2 decreases gradually with time (heartbeat frequency) before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

[The effectiveness of different respiration models to the amplitude of waveform information in arterial blood gas].

Objective: The objective is to find the characteristics of arterial blood sample waveform in different respiration models. Methods: Six post-operative patients with normal heart function and negative Allen test, were 4 male and 2 female, (59.00±16.64)year, (71.67±0.37)kg, left ventricular ejection fraction(LVEF) (61.33±2.16)%, had been placed the arterial catheterization and central venous catheterization for continuous collecting arterial in 3 different kinds of respiration models: normal breathing, no breathing and deep breathing. We selected two breaths cycles of waveform from each patient for data calculations of magnitudes and time interval. Compare the adjacent highest and lowest values of patients to verify whether there are periodic wave-like signal changes in arterial and venous blood gas in the three breathing states. In addition, statistical t-test analysis was performed on the change amplitude of the periodic wave-like signal of the patient's arterial and venous blood gas to compare whether there is a difference. Results: The heart beat numbers for drawing blood into pipe were 15-16, and all covered more than 2 breathing cycles. There were significant changes of arterial PaO2 (i.e. the highest high values compare to the next lowest values, P<0.05) in three different breathing models(normal, no breathing and high breathing), the magnitudes of which were (9.96±5.18)mmHg, (5.33±1.55)mmHg and (13.13±7.55)mmHg, with (8.09±2.43)%, (5.29±2.19)% and (10.40±2.68)% from their mean respectively. PO2 in venous blood gas did not show wavy changes under normal breathing, 20 s breath holding and high tidal volume ventilation. The amplitudes were (1.63 ± 0.41) mmHg, (1.13 ± 0.41) mmHg and (1.31 ± 0.67) mmHg, which were (3.91 ± 1.22)%, (2.92 ± 1.12)%, (3.33 ± 1.81)%, respectively, which were significantly lower than that of arterial blood gas under the same state, but there was no significant difference between groups. Conclusion: With continuous beat-by-beat arterial blood sampling and ABG analyzing method in three different breathing models, We obtain a clear evidence of the biggest periodic parameters ABG waveform in high breathing models, which followed by normal breathing models, no breathing was the smallest, and the wave variation amplitude of venous oxygen partial pressure was not obvious in the three respiratory states, which implies the oscillatory information of the arterial blood with comes from the gas exchanging in the lung.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates I-The group difference of partial pressure of oxygen and carbon dioxide between umbilical artery and vein in newborns].

Objective: The fetus has no actual respiration, and the newborn begins to breathe after birth. We assume that the first breath dominantly generated by hypoxia. In this study, the changes and lowest limit of blood oxygen partial pressureof umbilical artery (PuaO2) after chemoreceptor were analyzed to explore the mechanism of neonatal spontaneous breathing. Methods: With signed consent form by all fetal parents before birth, 14 newborns successfully completed the umbilical artery or vein catheterization and drawn blood according to the heartbeat. All blood samples analyzed by blood gas analyzer,calculated and analyzed the similarities and differences between umbilical vein(Puv) and umbilical artery(Pua). Results: Although we completed 14 newborns, there were only 9 cases of umbilical artery samples and 8 cases of umbilical vein samples were collected. Only 3 cases collected both Pua and Puv blood samples at the same time (see serial paper II). PuaO2 in gradually decreased with time (heartbeat frequency), until Pua contracted after spontaneous breathing produced about 8~10 heartbeats, and then could not get enough blood samples. Only 3 newborns were able to take blood samples after spontaneous breathing for 8~10 heartbeats, and their PuaO2 were jumped to 186.0, 137.0 and 93.8 mmHg respectively. The mean value of PuaO2 was (25.94±6.79, 18.04~37.51)mmHg, the highest value was (29.11±6.46, 23.00~45.90)mmHg, and the lowest value was (21.34±5.54, 14.00~33.60)mmHg. Although PuvO2 decreased gradually with time (heartbeat) too, most of them also showed the tendency of alternately rising and falling with the regularity of mother's respiration. The mean value of PuvO2 was (53.35±21.35, 32.56~100.73)mmHg, the highest value was (90.38±48.44, 43.40~153.00)mmHg, and the lowest value was (36.96±14.90, 24.80~73.80)mmHg. Although there were large individual differences, the mean, highest and lowest values of PuvO2 were significantly higher than those of PuaO2 (P<0.05); although PuvCO2 slightly lower than PuaCO2, it was no significant difference (P>0.05). Conclusion: PuaO2 decreases gradually with time before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

[The experimental evidence of waveform information in arterial blood gas by beat-by-beat sampling method in human body-the differences of waveform information between arterial and venous blood samples].

Objective: The arterial blood with the oscillatory information comes from the right heart system after gas exchanging in the lung. However, the evidence of the waveform of venous ABG is lack. The objectives of this article are to compare the different information between arterial and venous beat-by-beat blood sample at the same time. Methods: Six post-operative patients with normal heart function and negative Allen test, had been placed the arterial catheterization and central venous catheterization directly connected to pre-heparin plasticpipes for continuous collecting arterial and venous blood. We twisted the 2 pipes into helix formation. After drawing arterial and venous blood with syringes in one heart beat with one helix at the same time, totally 15 heart beats, clipping the pipes with forceps, we put the helix pipe into icedwater at once and analyses PaO2, PaCO2, pH and SaO2 as soon as possible. We selected two breathscycles of waveform from each patient for data calculations of magnitudes and time interval. Results: The heart beat numbers for drawing blood into pipe were 15~16, and all covered more than 2 breathing cycles. There were significant changes of arterial PaO2(i.e. the highest high values compare to the next lowestvalues, P<0.05), but no significant changes in venous blood(P>0.05). The magnitudes of changing PaO2 in arterial and venous blood sample were (9.96±5.18)mmHg and (1.63±0.41)mmHg with significant variance(P=0.010), and they were (8.09±2.43)% and (3.91±1.22)%from their mean with significant variance(P=0.009) respectively. Conclusion: With continuous beat-by-beat arterial and venous blood sampling and ABG analyzing method at the same time, we obtain a clear evidence of periodic parameters ABG waveform, which following breathing cycle, but no clear ABG waveform of the periodic parameters in the venous blood samples, which implies the oscillatory information of the arterial blood with comes from the gas exchanging in the lung.

[Preliminary experimental study on the influence of different tidal volume and frequency of normal minute ventilation on the dynamic changes of carotid blood oxygen in living goats].

Objective: On the basis of preliminarily verifying the use of ultra-fast reaction polymer matrix optical fiber oxygen sensor and its measuring system to record the continuous and dynamic changes of carotid artery oxygen partial pressure (PaO2), in order to analyze and discuss the influence of lung ventilation on the continuous and dynamic changes of PaO2, we designed a whole animal experimental study in vivo. Methods: Four hybrid goats were selected, and the skin was cut and exposed directly under general anesthesia and tracheal intubation. The oxygen sensor, connected with the measuring system, was inserted directly into the left carotid artery to continuously record the dynamic changes of PaO2. With normal minute ventilation,mechanical ventilation is implemented through three tidal volumes: normal tidal volume (VT=15 ml/kg, Rf=20 bpm), half tidal volume (halved VT, doubled Rf) and double tidal volume (doubled VT, halved Rf). Each tidal volume was stable for 10~15 min respectively. We analyzed and calculated the average values of PaO2, the fluctuation magnitudes of PaO2 changes between breaths of last 180 s and the delay times of lung-carotid artery were. We analyzed the effects of different tidal volumes. Results: The heart rate and blood pressure of living goats were maintained stable during the mechanical ventilation experiment with normal ventilation volume Lung-carotid artery delay time is 1.4~1.8 s (about 3 heartbeats at this time). Under normal tidal volume of mechanical ventilation, the average value of PaO2 was (102.94±2.40, 99.38~106.16) mmHg, and the fluctuation range was (21.43±1.65, 19.21~23.59) mmHg, accounting for (20.80± 1.34, 18.65~22.22)% of the average value. Under the condition of halving tidal volume, the average value of PaO2 was maintained at (101.01±4.25, 94.09~105.66) mmHg, which was slightly decreased but not significant (P>0.05 compared with normal mechanical ventilation), but the fluctuation range of PaO2 was significantly reduced to (18.14±1.43, 16.46~20.05) mmHg, accounting for 17.5% of the average value. Under double tidal volume mechanical ventilation, although the average value of PaO2 increased slightly remained at (106.42±4.74, 101.19~114.08) mmHg (P>0.05 compared with normal mechanical ventilation and P<0.05 compared with half tidal volume mechanical ventilation), the fluctuation magnitude of PaO2 increased significantly to (26.58±1.88, 23.46~28.46)mmHg. Conclusion: Inspiration and expiration of normal lung ventilation are the initial factors for the increase and decrease of PaO2 in carotid artery. Under normal ventilation, halving tidal volume and doubling tidal volume significantly changed the fluctuation magnitude of PaO2, but the average value of PaO2 changed only slightly, while the lung-carotid delay time was similar.

[Ultra-fast response polymer optical fiber oxygen measurement device and its preliminary experimental report on continuous dynamic change of arterial oxygen partial pressure under mechanical ventilation in living animals].

Objective: We tried to implant the ultra-fast polymer optical fiber chemical oxygen sensor （POFCOS） into arterial blood vessel,connect with photoelectric conversion measurement system to record the continuous dynamic rapid changes of arterial PO2(PaO2) in whole living animals. It should be the experimental evidence for the new theory of holistic integrative physiology and medicine(HIPM) forexplain the mechanism of respiratory control and regulation in whole circusof respiration-circulation-metabolism. Methods: ①Fabrication of ultrafast POFCOS, calibration and its measuring system: The distal part of 2 m optical fiber was heated and pulled until it became a tapered tip. After cleaning and drying, the tip of 1 mm tapered optical fiber was dip-coated into the luminophore doped polymer solution, then was slowly pumped out while solvent was quickly evaporated to form an oxygen sensing tip, which was dried at room temperature for 24 hours. ②Animal experiments: Under general anesthesia and intubation, goatwas mechanically ventilated with 40%~60% oxygen. We exposed both right and left carotid arteries and the left femoral artery by skin cutting, and inserted the POFCOS directly into the arteries via indwelling catheter. The end of POFCOS were connected to the personal computer through optical fiber, excitation and detection Y-type optical fiber coupler through photoelectric conversion, so as we can realize the continuous dynamic response of living goat carotid PaO2 under mechanical ventilation. We mainly analyzed the intra-breath wave-form alternate increase and decrease of PaO2 and their time delay between lung and carotid arteries.We completes breathing control whole loop to explain the mechanism of mutual breathing and the switching of inspiration and exhalation. Results: The POFCOS has a very fast T90 response time was set 100 ms for liquid. When the heart rate of 40%~60% oxygen mechanical ventilated living goat was ~110 bpm, the PaO2 of left and right carotid artery showed a same wave-sizeup and down following with the inspiration and expiration of ventilator, with a range of up to 15 mmHg. There weresignificant noises of PaO2 change recorded in the left femoral artery. The lung-carotid artery time delay is 1.5~1.7 s after inhalation and exhalation, PaO2 at both left and right carotid arteries starts toincrease and decrease. After two-three heartbeats after the start of lung ventilation, thealternate up-down wave-form information of the arterialized pulmonary vein blood after pulmonary capillaries waspumpedby left ventricle to the position of peripheral chemoreceptors,thus realizing the whole cycle of inhalation and exhalation. It alternately interrupted inhalation, i.e. switching inhalation to exhalation, and then interrupted exhalation,i.e. switching exhalation to inhalation. Conclusion: The ultra-fast reactive implantableoxygen sensor and its measuring system can measure the physiological waveform changes of PaO2 in living animals, which can provide experimental evidence for explaining the mechanism of switching of inspiration-expiration in HIPM.

Capacitive Removal of Fluoride Ions via Creating Multiple Capture Sites in a Modulatory Heterostructure.

Fluoride pollution has become a major concern because of its adverse effects on human health. However, the removal capacity of defluorination agents in traditional methods is far from satisfactory. Herein, capacitive removal of F- ions via creating multiple capture sites in a modulatory heterostructure has been originally demonstrated. The heterostructure of uniformly dispersed Al2O3 coating on hollow porous nitrogen-doped carbon frameworks was precisely synthesized by atomic layer deposition. An exceptional F- ion removal efficiency at 1.2 V (95.8 and 92.9% in 5 and 10 mg/L F- solutions, respectively) could be finally achieved, with a good regeneration ability after 20 consecutive defluorination cycles. Furthermore, we investigated the removal mechanisms of F- ions by in situ Raman, in situ X-ray diffraction, and ex situ X-ray photoelectron spectroscopy measurements. The promotional removal capacity was realized by the multiple capture sites of the reversible conversion of Al-F species and the insertion of F- ions into the carbon skeleton. This work offers an important new pathway and deep understanding for efficient removal of F- ions from wastewater.

SIRT3 alleviates neuropathic pain by deacetylating FoxO3a in the spinal dorsal horn of diabetic model rats.

BACKGROUND: The underlying mechanisms of neuropathic pain remain unclear. This work aimed to investigate the role of Sirtuin3 (SIRT3), an nicotinamide adenosine dinucleotide+-dependent histone deacetylase, in the development of neuropathic pain induced by type 2 diabetes mellitus (T2DM) and to explore the associated mechanisms. METHODS: Diabetic neuropathic pain (DNP) in rats was induced by high-fat diet/low-dose streptozotocin. The pain behaviors were examined using the von Frey and Hargreaves tests. The levels of SIRT3, manganese superoxide dismutase (MnSOD) and catalase (CAT) were determined using Western blot and RT-qPCR. The acetylation, phosphorylation and ubiquitination of forkhead box class O3a (FoxO3a) were analyzed by immunoprecipitation and Western blot. RESULTS: SIRT3 expression and activity were significantly reduced in the spinal dorsal horn of DNP model rats. Overexpression of spinal SIRT3 reversed the pain hypersensitivity in the DNP model rats, but knockdown of spinal SIRT3 mimicked the pain effect, eliciting pain hypersensitivity in normal rats. Moreover, overexpression of spinal SIRT3 in DNP model rats increased the FoxO3a level and upregulated the antioxidant genes MnSOD and CAT by deacetylating FoxO3a and inhibiting FoxO3a phosphorylation and ubiquitination. Knockdown of spinal SIRT3 in normal rats decreased the FoxO3a level and downregulated MnSOD and CAT by inhibiting the deacetylation of FoxO3a and further increasing FoxO3a phosphorylation and ubiquitination. CONCLUSIONS: These results suggest that, by deacetylating FoxO3a and further reducing its phosphorylation, ubiquitination and degradation in the spinal dorsal horn, SIRT3 stabilizes FoxO3a protein and inhibits oxidative stress, resulting in pain alleviation in T2DM model rats.

Effect of Ibrutinib on the IFN Response of Chronic Lymphocytic Leukemia Cells.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has profound activity in chronic lymphocytic leukemia (CLL) but limited curative potential by itself. Residual signaling pathways that maintain survival of CLL cells might be targeted to improve ibrutinib's therapeutic activity, but the nature of these pathways is unclear. Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib. IFN signaling in CLL cells from human patients was not prevented by ibrutinib in vitro or in vivo, but ISG expression was significantly attenuated in vitro. ISGs such as CXCL10 that require concomitant activation of NF-κB were decreased when this pathway was inhibited by ibrutinib. Other ISGs, exemplified by LAG3, were decreased as a result of inhibited protein translation. Effects of IFN on survival remained intact as type I and II IFN-protected CLL cells from ibrutinib in vitro, which could be prevented by ruxolitinib and IFNR blocking Abs. These observations suggest that IFNs may help CLL cells persist and specific targeting of IFN signaling might deepen clinical responses of patients on ibrutinib.

Transcriptome analysis reveals potential immune function-related regulatory genes/pathways of female Lubo goat submandibular glands at different developmental stages.

BACKGROUND: The submandibular glands, as major salivary glands, participate in rumen digestion in goats. Sialic acid, lysozyme, immunoglobulin A (IgA), lactoferrin and other biologically active substances secreted in the submandibular glands were reported in succession, which suggests that the submandibular gland may have immune functions in addition to participating in digestion. The aim of this study was to map the expression profile of differentially expressed genes (DEGs) at three different stages by transcriptome sequencing, screen immune-related genes and pathways by bioinformatics methods, and predict the immune function of submandibular glands at different developmental stages. METHODS: Nine submandibular gland tissue samples were collected from groups of 1-month-old kids, 12-month-old adolescent goats and 24-month-old adult goats (3 samples from each group), and high-throughput transcriptome sequencing was conducted on these samples. The DEGs among the three stages were screened and analysed. Key genes and signalling pathways were selected via protein-protein interaction (PPI) network analysis. RESULTS: The results revealed 2,706, 2,525 and 52 DEGs between 1-month-old and 12-month-old goats, between 1-month-old and 24-month-old goats, and between 12-month-old and 24-month-old goats, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that most of the DEGs were enriched in immune- related GO terms and pathways. Based on functional enrichment analysis and network analysis, 10 genes (PTPRC, CD28, SELL, LCP2, MYC, LCK, ZAP70, ITGB2, SYK and CCR7), two signalling pathways (the T cell receptor signalling pathway and the NF-κß signalling pathway) and eight GO terms (T cell receptor signalling pathway, neutrophil mediated immunity, B cell mediated immunity, regulation of alpha-beta T cell activation, positive regulation of T cell proliferation, regulation of leukocyte differentiation, positive regulation of antigen receptor-mediated signalling pathway, positive regulation of lymphocyte proliferation) that may play key roles in the immune functions of the goat submandibular glands at different developmental stages were identified. Moreover, we found that eight antibacterial peptide-encoding genes were downregulated in the tuberculosis and salivary secretion pathways, while all immunoglobulins were upregulated in 10 immune system pathways. These findings indicate that the submandibular glands may be important immunological organs during the growth process of goats and that the immune function of these glands gradually weakens with age up to 12 months but remains relatively stable after 12 months of age. Overall, this study will improve our understanding of transcriptional regulation related to goat submandibular gland immune function.