Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.

Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1ß, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.

MFPred: prediction of ncRNA families based on multi-feature fusion.

Non-coding RNA (ncRNA) plays a critical role in biology. ncRNAs from the same family usually have similar functions, as a result, it is essential to predict ncRNA families before identifying their functions. There are two primary methods for predicting ncRNA families, namely, traditional biological methods and computational methods. In traditional biological methods, a lot of manpower and resources are required to predict ncRNA families. Therefore, this paper proposed a new ncRNA family prediction method called MFPred based on computational methods. MFPred identified ncRNA families by extracting sequence features of ncRNAs, and it possessed three primary modules, including (1) four ncRNA sequences encoding and feature extraction module, which encoded ncRNA sequences and extracted four different features of ncRNA sequences, (2) dynamic Bi_GRU and feature fusion module, which extracted contextual information features of the ncRNA sequence and (3) ResNet_SE module that extracted local information features of the ncRNA sequence. In this study, MFPred was compared with the previously proposed ncRNA family prediction methods using two frequently used public ncRNA datasets, NCY and nRC. The results showed that MFPred outperformed other prediction methods in the two datasets.

Serum metabolomics analysis in patients with alcohol dependence.

Objective: Alcohol dependence (AD) is a chronic recurrent mental disease caused by long-term drinking. It is one of the most prevalent public health problems. However, AD diagnosis lacks objective biomarkers. This study was aimed to shed some light on potential biomarkers of AD patients by investigating the serum metabolomics profiles of AD patients and the controls. Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to detect the serum metabolites of 29 AD patients (AD) and 28 controls. Six samples were set aside as the validation set (Control: n = 3; AD group: n = 3), and the remaining were used as the training set (Control: n = 26; AD group: n = 25). Principal component analysis (PCA) and partial least squares discriminant analysis (PCA-DA) were performed to analyze the training set samples. The metabolic pathways were analyzed using the MetPA database. The signal pathways with pathway impact >0.2, value of p <0.05, and FDR < 0.05 were selected. From the screened pathways, the metabolites whose levels changed by at least 3-fold were screened. The metabolites with no numerical overlap in their concentrations in the AD and the control groups were screened out and verified with the validation set. Results: The serum metabolomic profiles of the control and the AD groups were significantly different. We identified six significantly altered metabolic signal pathways, including protein digestion and absorption; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; linoleic acid metabolism; butanoate metabolism; and GABAergic synapse. In these six signal pathways, the levels of 28 metabolites were found to be significantly altered. Of these, the alterations of 11 metabolites changed by at least 3-fold compared to the control group. Of these 11 metabolites, those with no numerical overlap in their concentrations between the AD and the control groups were GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid and L-glutamine. Conclusion: The metabolite profile of the AD group was significantly different from that of the control group. GABA, 4-hydroxybutanoic acid, L-glutamic acid, citric acid, and L-glutamine could be used as potential diagnostic markers for AD.

A multivariate multi-step LSTM forecasting model for tuberculosis incidence with model explanation in Liaoning Province, China.

BACKGROUND: Tuberculosis (TB) is the respiratory infectious disease with the highest incidence in China. We aim to design a series of forecasting models and find the factors that affect the incidence of TB, thereby improving the accuracy of the incidence prediction. RESULTS: In this paper, we developed a new interpretable prediction system based on the multivariate multi-step Long Short-Term Memory (LSTM) model and SHapley Additive exPlanation (SHAP) method. Four accuracy measures are introduced into the system: Root Mean Square Error, Mean Absolute Error, Mean Absolute Percentage Error, and symmetric Mean Absolute Percentage Error. The Autoregressive Integrated Moving Average (ARIMA) model and seasonal ARIMA model are established. The multi-step ARIMA-LSTM model is proposed for the first time to examine the performance of each model in the short, medium, and long term, respectively. Compared with the ARIMA model, each error of the multivariate 2-step LSTM model is reduced by 12.92%, 15.94%, 15.97%, and 14.81% in the short term. The 3-step ARIMA-LSTM model achieved excellent performance, with each error decreased to 15.19%, 33.14%, 36.79%, and 29.76% in the medium and long term. We provide the local and global explanation of the multivariate single-step LSTM model in the field of incidence prediction, pioneering. CONCLUSIONS: The multivariate 2-step LSTM model is suitable for short-term prediction and obtained a similar performance as previous studies. The 3-step ARIMA-LSTM model is appropriate for medium-to-long-term prediction and outperforms these models. The SHAP results indicate that the five most crucial features are maximum temperature, average relative humidity, local financial budget, monthly sunshine percentage, and sunshine hours.

Wavelength-locked continuous-wave and Q-switched Ho:CaF2 laser at 2100.5 nm.

In this paper, we demonstrated a linewidth-narrowed continuous-wave (CW) and acousto-optical Q-switched Ho:CaF2 laser for the first time. With a volume Bragg grating, a maximum CW output power of 6.94 W at 2100.5 nm, and slope efficiency of 57.9%, an FWHM linewidth of 0.31 nm was obtained. When absorbed pump power was 13.2 W, the maximum average output powers of 6.08 W, 5.9 W, and 5.71 W were achieved in a Q-switched Ho:CaF2 laser under pulse repetition frequencies of 10 kHz, 5 kHz, and 3 kHz, corresponding to the slope efficiencies of 51.2%, 49.6%, and 48.5%, respectively. The minimum pulse width of 54 ns was achieved at pulse repetition frequency of 3 kHz.

High-efficiency 2 µm continuous-wave laser in laser diode-pumped Tm3+, La3+: CaF2 single crystal.

A Tm3+, La3+: CaF2 single crystal was grown, and its spectral properties and laser performance were investigated. Under diode end-pumping, a continuous-wave laser has been demonstrated. The slope efficiency of up to 67.8% was first achieved in the co-doping crystal, which is close to twice the theoretical quantum efficiency. A maximum output power of 4.269 W and a broad tunable range of 192 nm were also obtained, indicating this system is a promising candidate for highly efficient ∼2 µm lasers.

Highly-efficient mid-infrared CW laser operation in a lightly-doped 3 at.% Er:SrF2 single crystal.

3 at.% Er:SrF2 laser crystals with high optical quality were successfully grown using the temperature gradient technique (TGT). The intense mid-infrared emission was observed around 2.7 µm with excitation by a 970 nm LD. Based on the Judd-Ofelt theory, the emission cross-sections of the 4I13/2-4I11/2 transition were calculated by using the Fuchtbauer-Ladenburg (FL) method. Efficient continuous-wave laser operation at 2.8 µm was achieved with the lightly-doped 3 at.% Er:SrF2 crystal pumped by a 970 nm laser diode. The laser output power reached up to 1.06 W with a maximum slope efficiency of 26%.

[Clinical significance of 5-HT and DA levels in serum and cerebrospinal fluid of the patients with delayed encephalopathy after acute carbon monoxide poisoning].

OBJECTIVE: To explore the changes and the clinical significance of 5-hydroxytryptamine (5-HT), dopamine (DA) levels in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy (DEACMP) after acute carbon monoxide poisoning. METHODS: The dynamic detection of 5-HT and DA levels in serum and CSF from 42 patients with DEACMP was performed with high performance liquid chromatography (HPLC). The condition changes of patients with DEACMP were analyzed with three types of scales: the activity of daily living scale (ADL), information memory concentration test (IMCT) and Hasegawa's dementia scale (HDS); these changes were compared with those from 38 other encephalopathy patients and 38 non-encephalopathy patients, respectively. RESULTS: Before treatment, the serum 5-HT and DA levels [(662.61 ± 178.50) and (155.74 ± 60.32) nmol/L, respectively] of DEACMP group were both significantly lower than those [(914.08 ± 198.04) and (225.70 ± 48.53) nmol/L] of non-encephalopathy group (P < 0.05); the serum DA level of DEACMP group was also significantly lower than that [(243.57 ± 66.94) nmol/L] of other encephalopathy group (P < 0.05); the serum 5-HT level of DEACMP group was not significantly different from that [(729.54 ± 299.87) nmol/L] of other encephalopathy group (P > 0.05). After treatment, the serum 5-HT and DA levels [(714.08 ± 170.47) and (192.18 ± 33.07 nmol/L, respectively)] of DEACMP group elevated to various extent, but only serum DA level was significantly higher than that before treatment (P < 0.05). Before treatment, the CSF 5-HT and DA levels of DEACMP group were significantly lower than those of non-encephalopathy group and those of other encephalopathy group (P < 0.05). After treatment, the CSF 5-HT level (232.44 ± 54.28 nmol/L) was similar to normal level and significantly higher than that before treatment (P < 0.05); the CSF DA level [(56.83 ± 12.85) nmol/L] of DEACMP group increased only slightly (P > 0.05). In DEACMP group, ADL score (50.64 ± 7.23), HDS score (8.55 ± 8.08) and IMCT score (4.95 ± 7.30) before treatment were significantly different from those (8.5 ± 8.08, 4.95 ± 7.30 and 15.64 ± 10.90) after treatment (P < 0.01). In DEACMP group, there wasa negative correlation between DA level changes and HDS score changes, when the DA levels and HDS scores before treatment were compared with those after treatment (P < 0.05). CONCLUSION: The dynamic changes of 5-HT and DA levels in serum and CSF of patients with DEACMP consisted basically with the patient's condition change. The dynamically detected 5-HT and DA levels can be used as the biological indicators to reflect the condition change and treatment effects of DEACMP patients.

[The changes of soluble interleukin-2 receptor in serum and cerebrospinal fluid of patients with delayed encephalopathy after acute carbon monoxide poisoning].

OBJECTIVE: To explore the changes of soluble interleukin-2 receptor(sIL-2R) in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS: There were 31 patients with DEACMP, 32 patients with other encephalopathy and 31 controls in this study. The levels of sIL-2R in serum and CSF were detected by ELISA. RESULTS: Serum sIL-2R in patients with DEACMP[(329.21 +/- 160.99)U/ml] was significantly higher than that in control[(115.67 +/- 89.58) U/ml, P < 0.05)], but not significantly different from that in the other encephalopathy group[(367.50 +/- 123.14) U/ml, P > 0.05)]. CSF sIL-2R in patients with DEACMP[(54.48 +/- 43.04) U/ml] measured a little before discharge was significantly lower than that in patients with the other encephalopathy[(110.24 +/- 76.56) U/ml, P < 0.05)], but not significantly different from that in the control group[(34.96 +/- 22.70)U/ml, P > 0.05)]. At the pre-discharged period, CSF sIL-2R in patients with DEACMP[(100.26 +/- 93.65) U/ml] was significantly higher than that at the early stage of hospitalization[(52.28 +/- 43.31) U/ml, P < 0.05)]. No significant difference in serum sIL-2R was found between early stage of hospitalization[(338.34 +/- 161.53) U/ml] and pre-discharge [(351.31 +/- 175.93) U/ml, P > 0.05)]. CONCLUSION: The occurrence of DEACMP may be related with immunopathological damage. The sIL-2R levels in serum and CSF may give information about the state of immunological function of the patients with DEACMP and may contribute to determining the patient's condition and prognosis.