Quantum chemistry calculation-aided discovery of potent small-molecule mimics of glutathione peroxidases for the treatment of cisplatin-induced hearing loss.

Hearing loss (HL) is a health burden that seriously affects the quality of life of cancer patients receiving platinum-based chemotherapy, and few FDA-approved treatment specifically targets this condition. The main mechanisms that contribute to cisplatin-induced hearing loss are oxidative stress and subsequent cell death, including ferroptosis revealed by us as a new mechanism recently. In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the potential of GPx mimics as a therapeutic strategy against cisplatin-induced hearing loss. The application of quantum chemistry (QC) calculations in the study of GPx mimics sheds light on the development of new, innovative treatments for hearing loss.

Chromosome-level genome assembly of the yellow-cheek carp Elopichthys bambusa.

Yellow-cheek carp (Elopichthys bambusa) is a typical large and ferocious carnivorous fish endemic to East Asia, with high growth rate, nutritional value and economic value. In this study, a chromosome-level genome of yellow-cheek carp was generated by combining PacBio reads, Illumina reads and Hi-C data. The genome size is 827.63 Mb with a scaffold N50 size of 33.65 Mb, and 99.51% (823.61 Mb) of the assembled sequences were anchored to 24 pseudo-chromosomes. The genome is predicted to contain 24,153 protein-coding genes, with 95.54% having functional annotations. Repeat elements account for approximately 55.17% of the genomic landscape. The completeness of yellow-cheek carp genome assembly is highlighted by a BUSCO score of 98.4%. This genome will help us understand the genetic diversity of yellow-cheek carp and facilitate its conservation planning.

Rural-urban differences in prevalence and correlates of suicidal ideation in adolescent patients with depression in a large sample of Chinese.

BACKGROUND: Suicidal ideation (SI) is severe comorbidity of depression that has been extensively studied in the past. Residence differences between SI have rarely been systematically studied, especially in parental rearing behavior. This large-scale explored the residence differences in the prevalence and correlation of SI adolescent patients with depression. METHODS: A total of 1417 patients with depression were recruited, and their demographic data and clinical data were collected. The Children's Depression Inventory (CDI) and the Egna Minnen Beträffande Uppfostran (EMBU) scale were used to assess depression, and parental rearing behavior, respectively. RESULTS: The prevalence of suicidal ideation was higher in urban patients than in rural patients (43.7 % vs.37.7 %, P < 0.05). Patients with SI scored higher on total CDI scores, parental punishment, parental rejection, and paternal overprotection compared to their respective patients without SI. In the urban group, patients with SI had lower parental emotional warmth scores and higher parental intervention scores compared to patients without SI. Logistic regression analysis showed that total CDI score, gender, alcohol consumption, father's emotional warmth, father's rejection, and mother's intervention were significantly associated with SI in urban patients (P < 0.05); total CDI score and mother's rejection were significantly associated with SI in rural patients (P < 0.05). LIMITATIONS: No causal relationship could be drawn due to the cross-sectional design. CONCLUSIONS: The results of this study showed significant residential differences in risk and associated factors for SI among adolescents with depression. Focusing on the parenting styles of adolescent patients can help with the early identification and intervention of SI.

Association of high BMI with subclinical hypothyroidism in young, first-episode and drug-naïve patients with major depressive disorder: a large-scale cross-sectional study.

Thyroid dysfunction is known to be associated with obesity, but the reliability of this relationship is easily affected by drug treatment, age, and subclinical hypothyroidism (SCH) with no apparent symptoms. Our research aims to compare obese and overweight BMI ranges with SCH and without SCH in a large sample of young, first-episode and drug-naïve (FEDN) patients with major depressive disorder (MDD), which has received little systemic investigation. A total of 1289 FEDN MDD young outpatients were recruited for this study. Serum thyroid function and lipid level parameters were measured; HAMD and PANSS scales were used to assess patients' depression and positive symptoms. A self-administered questionnaire collected other clinical and demographic data. The prevalence of SCH in FEDN MDD young patients was 58.26%. Compared to patients without SCH, the patients with SCH had a more prolonged illness duration, higher BMI levels, increased prevalence of overweight and obesity, higher HAMD score and PANSS-positive symptom scores, higher levels of TG, TC, LDL-C, and lower levels of HDL-C. Further logistic regression indicated that overweight BMI, obese BMI, illness duration, HAMD score, HDL-C, and TC were significantly associated with SCH. Our results indicate that obesity and overweight may be associated with SCH in young, FEDN MDD patients. The importance of regular thyroid function assessment in young FEDN MDD patients with high BMI should be taken into account.

[Comparison of artificial neural network with compatible biomass model for predicting aboveground biomass of individual tree]. / 人工神经网络与相容性生物量模型预测单木地上生物量的比较.

Forest biomass is an important index in forest development planning and forest resource monitoring. In order to provide a more efficient and low-biased method for estimating individual tree biomass, we introduced artificial neural network here. We used the data of aboveground biomass of 101 Larix olgensis trees harvested from the Dongzhelenghe Forest Farm in Heilongjiang Province to develop four aggregation model systems (AMS), based on different combination of the variables (diameter at breast height, tree height, crown width). The weighted functions were used to eliminate heteroscedasticity. Then, we trained artificial neural network (ANN) biomass model based on the optimal combination. The models were tested by the leave-one-out cross-validation method to compare the accuracy of the two biomass estimation methods. The results showed that biomass model based on only one variable, diameter at breast height, could accurately estimate the biomass of L. olgensis. Adding two indices, tree height and crown width, could improve the fitting performance of models, with AMS4 performing the best among the four addictive model systems. The biomass models developed by the two methods both could estimate biomass at tree level accurately, with the coefficient of determination (R2) of each component was higher than 0.87. Compared with the AMS4, R2 of leaf biomass model was about 0.05 higher, and that of other organs were also about 0.01 higher in artificial neural network model system. In addition, the root mean square error (RMSE) and other indicators were also significantly smaller. For example, the RMSE of tree stem and aboveground biomass were smaller by 2.135 kg and 3.908 kg, respectively. The model's validation statistics mean relative error (MRE) performed better. In general, ANN was a flexible and reliable biomass estimation method, which was worthy consideration when predicting tree component biomass or aboveground biomass.

Association of serum lipid levels with psychotic symptoms in first-episode and drug naïve outpatients with major depressive disorder: a large-scale cross-sectional study.

Background Major depressive disorder (MDD) is a prevalent psychiatric disorder, with increasing evidence that patients with MDD display psychotic symptoms. Studies have shown the association between lipid levels and MDD, but few have explored the relationship between lipids and psychotic symptoms in MDD. The objective of this study was to compare the differences of lipid levels between patients with psychotic major depressive disorder (PMD) and those with non-psychotic major depressive disorder (NPMD) in first-episode and drug-naive (FEDN) MDD patients. Methods A total of 1718 outpatients with FEDN MDD were recruited. In addition to collecting basic information, their blood specimens were also collected to detect serum TC, HDL-C, TG, and LDL-C. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, and psychotic symptoms respectively. Results Compared to those with NPMD, those with PMD had higher scores on HAMD, HAMA, and more elevated serum TC, TG, and LDL-C levels, but lower HDL-C levels (all p < 0.05). Further logistic regression analysis showed that TG, the severity of depressive and anxiety symptoms were significantly associated with psychotic symptoms (p < 0.05). Limitations No causal relationship could be drawn due to the cross-sectional design. Conclusions Psychotic symptoms in patients with MDD may be predicted by lipid levels in the future. Our findings suggest that TG seems to predict the presence of current psychotic features among patients with FEDN MDD.

[Spatial and temporal variations of the responses of radial growth of Larix gmelinii to climate in the Daxing'anling Mountains of Northeast China]. / å¤§å ´å®‰å²­å ´å®‰è½å¶æ¾å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å“åº”çš„æ—¶ç©ºå˜åŒ–.

Following the distribution characteristics of Larix gmelinii in Daxing'anling Mountains, nine sampling sites along a latitude gradient were set up to analyze the spatial difference and temporal dynamic in the responses of radial growth of L. gmelinii to climate. Overall, the radial growth of L. gmelinii was positively correlated with the standardized precipitation evapotranspiration index (SPEI) in summer (June to August), summer precipitation, February SPEI, and February preci-pitation, but was negatively correlated with the March temperature. Spatially, in the southern area of the region with higher annual average temperature, the radial growth of L. gmelinii had a significant positive correlation with February SPEI. In the northern area with lower annual average tempera-ture, the radial growth of L. gmelinii was negatively correlated with the temperature in March. Temporally, the growth-climate relationship for L. gmelinii was unstable. In the area with higher annual average temperature, the positive effects of SPEI and precipitation, as well as the negative effects of temperature in summer on growth significantly enhanced with climate warming. In the area with lower annual average temperature, the negative response of growth to March temperature enhanced more obviously. Such a result indicated that climate change would alter growth-climate relationship, with great spatial variations. Our results suggested that radial growth of L. gmelinii would be limited in the future climate of warm and dry in the Daxing'anling Mountains. The growth of L. gmelinii might obviously decline in south due to summer water deficit and winter drought, and might be inhibited in north because of warm and dry winter.

Goose Nephritic Astrovirus Infection of Goslings Induces Lymphocyte Apoptosis, Reticular Fiber Destruction, and CD8 T-Cell Depletion in Spleen Tissue.

The emergence of a novel goose nephritic astrovirus (GNAstV) has caused economic losses to the Chinese goose industry. High viral load is found in the spleen of goslings infected with GNAstV, but pathological injuries to the spleen due to GNAstV are largely unknown. In this study, 50 two-day-old goslings were infected orally with GNAstV, and 50 goslings were treated with PBS as control. Spleens were collected at different times following infection to assess damage. GNAstV infection caused visceral gout and urate deposition in joints, and resulted in 16% mortality. GNAstV was found in the lymphocytes and macrophages within the spleen. Lymphocyte loss, especially around the white pulp, and destruction and decline in the number of reticular fibers was observed in GNAstV-infected goslings. Moreover, in GNAstV-infected goslings, ultrahistopathological examination found that splenic lymphocytes exhibited condensed chromatin and apoptotic bodies, and reticular cells displayed damage to plasma membrane integrity and swollen mitochondria. Furthermore, TUNEL staining confirmed apoptosis of lymphocytes, and the mRNA levels of Fas and FasL were significantly increased in the GNAstV-infected goslings. In addition, GNAstV infection reduced the number and protein expression of CD8. In conclusion, GNAstV infection causes lymphocyte depletion, reticular cell necrosis, reticular fiber destruction, lymphocyte apoptosis, and reduction in CD8 levels, which contribute to spleen injury.

Prevalence, risk factors and clinical correlates of suicidal ideation in adolescent patients with depression in a large sample of Chinese.

BACKGROUND: Suicidal ideation (SI) has a high risk in adolescents and is now a significant concern due to its problematic outcome. However, few systemic studies of suicidal ideation have been conducted in adolescent patients. Therefore, the current study was aimed to assess the prevalence and its clinical correlate of suicidal ideation among adolescent patients with depression. METHODS: A total of 1635 adolescent patients (748 males/ 887 females) with depression were recruited in this study. The clinical and demographic data were collected by a self-administered questionnaire. Suicidal ideation was assessed by interview. Children's Depression Inventory (CDI) was used to evaluate depressive symptoms, Adolescent Self-Rating Life Events Check List (ASLEC) was used to assess the stressful life events. RESULTS: The study showed that the prevalence of suicidal ideation in adolescent depression patients was 38.2% (625/1635). Compared to the non-SI patients, SI patients had greater scores on CDI and ASLEC, had inadequate sleeping time, and were more likely to be females. Further logistic regression analysis indicated that suicidal ideation in adolescent patients with depression was significantly associated with females, inadequate sleeping time, the severity of depression, and higher learning pressure. LIMITATIONS: No causal relationship could be drawn due to the cross-sectional design. CONCLUSIONS: Our results suggest a high prevalence of suicidal ideation in adolescents with depression. Moreover, the severity of depression, sex, sleep time, and learning pressure are all related to suicidal ideation. Early recognition and treatment of suicidal ideation can effectively prevent the occurrence of suicide among adolescent patients.

24-h intraocular pressure patterns measured by Icare PRO rebound in habitual position of open-angle glaucoma eyes.

PURPOSE: To measure the 24-h intraocular pressure (IOP) by Icare PRO rebound in healthy and primary open-angle glaucoma (POAG) eyes and compare it with non-contact tonometry (NCT). METHODS: Thirty POAG patients, who were under IOP-lowering treatment, and 30 healthy subjects were included. Participants were hospitalized overnight for the 24-h IOP measurement. IOPs were measured by Icare PRO and NCT according to a standard protocol every 2 h during 24 h. The 24-h IOP curve and IOP-related parameters were compared between Icare PRO and NCT groups in POAG and healthy eyes. RESULTS: The IOPs measured by Icare PRO in habitual position increased notably at 22:00 in the normal group and at 20:00 in the POAG group, reached peak at 0:00, stayed high until 4:00, and then decreased in both groups (all p < 0.05). The POAG patients had higher mean 24-h IOP, peak IOP, IOP fluctuation, and greater IOP change from supine to sitting position in the nocturnal period than those in the normal subjects even after adjusting for eyes, age, gender, CCT, and axial length (all p < 0.05). CONCLUSIONS: The Icare PRO provides a well-tolerated approach for 24-h IOP monitoring in habitual position. Twenty-four-hour IOP in habitual position is more sensitive for detecting high nocturnal IOP peaks and greater IOP fluctuation for POAG patients.

Immune-related gene expression in the kidneys and spleens of goslings infected with goose nephritic astrovirus.

Goose nephritic astrovirus (GNAstV) was first isolated in 2018, causing great economic losses to the goose industry. However, little is known about host immune response to GNAstV infection. In this study, forty 2-day-old goslings were randomly divided into 2 groups: infection and negative control groups. Each gosling in the infection group was challenged with 0.5 mL GNAstV-JSHA intramuscularly, whereas the gosling in the negative control group was inoculated with the same amount of PBS. Histopathological changes and virus location in the spleen and kidney were examined, and the expression of immune-related genes was determined by qPCR at 7 and 14 d after infection. Our results showed that GNAstV infection induced degeneration and necrosis of splenic lymphocytes and renal epithelial cells, and these cells were positive for the virus. In addition, GNAstV infection induced the activation of pattern recognition receptors (RIG-I, MDA-5, and TLR3) and key adaptor molecules (MyD88, MAVS, and IRF7) in the spleen and kidney, and upregulated the gene expression of interferon-α in the spleen and antiviral proteins (MX1, OASL, and IFITM3) in the spleen and kidney. Moreover, high expression levels of interleukin (IL)-1ß and IL-8 in the spleen and iNOS in the spleen and kidney were found. These results indicated that GNAstV infection activated host innate immune response. Furthermore, GNAstV infection increased the expression levels of CD8+, MHCI, and MHCII, indicating that adaptive immune response was activated. Besides, TGF-ß was highly expressed in the spleen and kidney, which may be an immune evasion strategy of GNAstV to cause infection. Interestingly, both IL-1ß and IL-6 mRNA levels were decreased in the kidney, which may help reduce kidney lesions. This is the first study to report changes in immune-related gene expression in response to GNAstV infection, and our results provide insights into viral pathogenesis.

Pseudorabies virus glycoprotein gE suppresses interferon-ß production via CREB-binding protein degradation.

Cyclic GMP-AMP synthase (cGAS) is a main sensor used to detect microbial DNA in the cytoplasm, which subsequently induces the production of interferon (IFN) via the cGAS/STING/IRF3 signaling pathway, leading to an antiviral response. However, some viruses have evolved multiple strategies to escape this process. Pseudorabies virus (PRV) is a double-stranded DNA virus belonging to the Alphaherpesvirinae subfamily, which can cause serious damage to the porcine industry. Many herpesvirus components have been reported to counteract IFN production, whereas little is known of PRV. In the present study, we found that PRV glycoprotein E (gE) was involved in counteracting cGAS/STING-mediated IFN production. Ectopic expression of gE decreased cGAS/STING-mediated IFN-ß promoter activity and the level of mRNA expression. Moreover, gE targeted at or downstream of IRF3 was found to inhibit IFN-ß production. However, gE did not affect the phosphorylation, dimerization and nuclear translocation of IRF3. Furthermore, gE is located on the nuclear membrane and could subsequently degrade CREB-binding protein (CBP). MG132, a proteasome inhibitor, decreased CBP degradation and restored the IFN-ß production induced by gE. Finally, gE-deleted PRV induced a higher level of IFN-ß production and reduced CBP degradation compared to wild-type PRV. Together, these results demonstrate that PRV gE can inhibit cGAS/STING-mediated IFN-ß production by degrading CBP to interrupt the enhanced assembly of IRF3 and CBP.

Mean amplitude of intraocular pressure excursions: a new assessment parameter for 24-h pressure fluctuations in glaucoma patients.

BACKGROUND: Intraocular pressure (IOP) is important in the pathogenesis of glaucoma and its circadian fluctuations are important in the disease management; however, there are no adequate parameters to describe the fluctuations. This study investigates a new parameter, mean amplitude of intraocular pressure excursion (MAPE), and compares its ability in assessing 24-h IOP fluctuations with other ocular parameters. METHODS: Only the right eye was evaluated in each of the 79 healthy people and 164 untreated patients with primary open angle glaucoma (POAG). Each participant underwent 24-h IOP monitoring by measuring IOP every 2 h. IOP fluctuations were expressed as MAPE calculations and currently used parameters included mean IOP, standard deviation of IOP, max difference and area under the circadian IOP curve. Comprehensive ophthalmologic examinations were also performed. Associations between visual field deficits and IOP fluctuation parameters were investigated via partial least squares (PLS) regression. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (ROC). RESULTS: Compared with healthy volunteers, the MAPE values in POAG patients were higher (4.16 ± 1.90 versus 2.45 ± 0.89, p < 0.01). In PLS regressions where visual field deficits were as dependent variable, MAPE had the highest score regarding variable importance in projection, and its standard regression coefficient was larger than other parameters. Diagnostic performance analysis showed the area under ROC of MAPE for glaucoma detection was 0.822 (0.768-0.868, p < 0.001). CONCLUSIONS: MAPE might be an effective parameter in clinic to characterise IOP circadian fluctuations.

Nuclear transporter karyopherin subunit alpha 3 levels modulate Porcine circovirus type 2 replication in PK-15 cells.

Entering the nucleus is important for Porcine circovirus type 2 (PCV2) replication. Karyopherins (KPNs) mediate the nuclear import of many cytoplasmic proteins. Our previous study showed that KPNA3 is involved in interferon production during PCV2 infection induced by Poly I:C and ISD (Interferon stimulatory DNA). However, it remains unclear whether PCV2 replication is associated with KPNA3. In the present study, knockdown of KPNA3 promoted the replication of PCV2, whereas overexpression of KPNA3 inhibited PCV2 replication in PK-15 cells. Furthermore, KPNA3 knockdown inhibited IRF3 and reduced the expression of antiviral genes including IFN-ß, ISG54, Mx1 and ISG56, while the opposite results were obtained after KPNA3 overexpression. KPNA3 knockdown also promoted p65 nuclear translocation and increased the mRNA expression of IL-10 and IL-1ß. These results suggested that KPNA3 facilitates IRF3 entry into the nucleus and the production of an antiviral response, resulting in PCV2 replication inhibition and blockage of NF-κB signal activation.

[Study on changes of intraocular pressure within 24 hours in primary open angle glaucoma and normal eyes].

OBJECTIVE: To analyze the discipline of intraocular pressure (IOP) variation, through circadian intraocular pressure monitoring in primary open-angle glaucoma (POAG) patients and normal controls, with a view to provide basis for individualized treatment of glaucoma. METHODS: Subjects were enrolled from the outpatients of Shanghai Beizhan Hospital and Eye and ENT Hospital of Fudan University, which were diagnosed as primary open angle glaucoma, from April 2006 to April 2009. Totally there were 102 cases of patients and 83 cases of normal volunteers. All the subjects accepted 24-hour IOP measurements using non-contact tonometer every two hours starting from 8:00 am. And the IOP between 00:00 to 06:00 am was measured in sitting position immediately after wake up. RESULTS: The differences of peak IOP [(16.0 ± 2.7) mm Hg of right eye and (16.2 ± 2.7) mm Hg of left eye in normal group; (25.3 ± 5.6) mm Hg of right eye and (24.8 ± 5.1) mm Hg of left eye in POAG group], valley IOP (11.1 ± 2.5) mm Hg of right eye and (11.0 ± 2.3) mm Hg of left eye in normal group; (16.3 ± 3.7) mm Hg of right eye and (16.2 ± 3.3) mm Hg of left eye in POAG group, average IOP (13.4 ± 2.5) mm Hg of right eye and (13.4 ± 2.5) mm Hg of left eye in normal group; (19.9 ± 4.3) mm Hg of right eye and (19.8 ± 3.8) mm Hg of left eye in POAG group), and IOP fluctuations (5.0 ± 1.6) mm Hg of right eye and (5.2 ± 1.7) mm Hg of left eye in normal group; (9.1 ± 3.6) mm Hg of right eye and (8.6 ± 3.8) mm Hg of left eye in POAG group between two groups were all of statistically significance (P < 0.01). Notably, the peak IOP of 59.6% in normal control group and 73.5% in POAG group were outside working hours, especially in the time period from 00:00 to 06:00 am. The peak value of 50% in normal group and 64.7% in POAG group located between 00:00 to 06:00 in the morning. CONCLUSIONS: By comparison and analysis, 24-hour intraocular pressure measurement could provide us pre-treatment basic state, so as to provide detailed information for individualized treatment. If possible, it is suggested that 24-hour IOP monitoring should be added as a routine examination of primary open angle glaucoma.