Preventing post-discharge suicides in psychiatric patients: insights from patients, lay healthcare supporters, and mental health professionals-a qualitative analysis.

BACKGROUND: Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. METHODS: This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. RESULTS: A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. CONCLUSIONS: Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients' needs and reduce post-discharge suicide. TRIAL REGISTRATION: Registration number: NCT04907669. Date of registration: May 26th,2021.

Face presentation at term: incidence, risk factors and influence on maternal and neonatal outcomes.

OBJECTIVES: The incidence, diagnosis, management and outcome of face presentation at term were analysed. METHODS: A retrospective, gestational age-matched case-control study including 27 singletons with face presentation at term was conducted between April 2006 and February 2021. For each case, four women who had the same gestational age and delivered in the same month with vertex position and singletons were selected as the controls (control group, n = 108). Conditional logistic regression was used to assess the risk factors of face presentation. The maternal and neonatal outcomes of the face presentation group were followed up. RESULTS: The incidence of face presentation at term was 0.14‰. After conditional logistic regression, the two factors associated with face presentation were high parity (adjusted odds ratio [aOR] 2.76, 95% CI 1.19-6.39)] and amniotic fluid index > 18 cm (aOR 2.60, 95% CI 1.08-6.27). Among the 27 cases, the diagnosis was made before the onset of labor, during the latent phase of labor, during the active phase of labor, and during the cesarean section in 3.7% (1/27), 40.7% (11/27), 11.1% (3/27) and 44.4% (12/27) of cases, respectively. In one case of cervical dilation with a diameter of 5 cm, we innovatively used a vaginal speculum for rapid diagnosis of face presentation. The rate of cesarean section and postpartum haemorrhage ≥ 500 ml in the face presentation group was higher than that of the control group (88.9% vs. 13.9%, P < 0.001, and 14.8% vs. 2.8%, P = 0.024), but the Apgar scores were similar in both sets of newborns. Among the 27 cases of face presentation, there were three cases of adverse maternal and neonatal outcomes, including one case of neonatal right brachial plexus injury and two cases of severe laceration of the lower segment of the uterus with postpartum haemorrhage ≥ 1000 ml. CONCLUSIONS: Face presentation was rare. Early diagnosis is difficult, and thus easily neglected. High parity and amniotic fluid index > 18 cm are risk factors for face presentation. An early diagnosis and proper management of face presentation could lead to good maternal and neonatal outcomes.

Membrane fusion, potential threats, and natural antiviral drugs of pseudorabies virus.

Pseudorabies virus (PrV) can infect several animals and causes severe economic losses in the swine industry. Recently, human encephalitis or endophthalmitis caused by PrV infection has been frequently reported in China. Thus, PrV can infect animals and is becoming a potential threat to human health. Although vaccines and drugs are the main strategies to prevent and treat PrV outbreaks, there is no specific drug, and the emergence of new PrV variants has reduced the effectiveness of classical vaccines. Therefore, it is challenging to eradicate PrV. In the present review, the membrane fusion process of PrV entering target cells, which is conducive to revealing new therapeutic and vaccine strategies for PrV, is presented and discussed. The current and potential PrV pathways of infection in humans are analyzed, and it is hypothesized that PrV may become a zoonotic agent. The efficacy of chemically synthesized drugs for treating PrV infections in animals and humans is unsatisfactory. In contrast, multiple extracts of traditional Chinese medicine (TCM) have shown anti-PRV activity, exerting its effects in different phases of the PrV life-cycle and suggesting that TCM compounds may have great potential against PrV. Overall, this review provides insights into developing effective anti-PrV drugs and emphasizes that human PrV infection should receive more attention.

Design, synthesis and biological evaluation of covalent peptidomimetic 3CL protease inhibitors containing nitrile moiety.

In this paper, a series of peptidomimetic SARS-CoV-2 3CL protease inhibitors with new P2 and P4 positions were synthesized and evaluated. Among these compounds, 1a and 2b exhibited obvious 3CLpro inhibitory activities with IC50 of 18.06 nM and 22.42 nM, respectively. 1a and 2b also showed excellent antiviral activities against SARS-CoV-2 in vitro with EC50 of 313.0 nM and 170.2 nM, respectively, the antiviral activities of 1a and 2b were 2- and 4-fold better than that of nirmatrelvir, respectively. In vitro studies revealed that these two compounds had no significant cytotoxicity. Further metabolic stability tests and pharmacokinetic studies showed that the metabolic stability of 1a and 2b in liver microsomes was significantly improved, and 2b had similar pharmacokinetic parameters to that of nirmatrelvir in mice.

New technique for detecting cracked teeth and evaluating the crack depth by contrast-enhanced cone beam computed tomography: an in vitro study.

BACKGROUND: Cracked teeth may cause various clinical symptoms depending on the extension depth of the crack and the subsequent bacterial infections. However, techniques to reliably determine the extension depths of cracks in teeth before treatment are lacking. The aim of this study was to develop a new technique based on contrast-enhanced cone beam computed tomography (CBCT) to improve the accuracy of crack depth evaluation in vitro. METHODS: We developed an in vitro artificial simulation model of cracked teeth. Pre-experimental CBCT (pre-CBCT), and micro-computed tomography (micro-CT) were first performed for all cracked teeth (n = 31). Contrast-enhanced CBCT was then performed by infiltrating the crack with ioversol under vacuum conditions. The sensitivities of pre-CBCT and contrast-enhanced CBCT for the diagnosis of cracked teeth were calculated. According to the K-means clusters, crack depths measured by micro-CT were changed into categorical variables. Bland-Altman plot and the intraclass correlation coefficient (ICC) were used to analyze the consistency of the crack depths between the pre-CBCT and contrast-enhanced CBCT, as well as the ICC between the contrast-enhanced CBCT and micro-CT. Receiver operating characteristic (ROC) curves were generated to assess the ability for predicting crack depth in the differential diagnosis using pre-CBCT and contrast-enhanced CBCT. Restricted cubic splines were also used to model the non-linear relationship between the crack depths of contrast-enhanced CBCT and micro-CT. RESULTS: The sensitivities of pre-CBCT and contrast-enhanced CBCT were 48.4%, and 67.7%, respectively. The ICC value of crack depth as measured by pre-CBCT and contrast-enhanced CBCT was 0.847 (95% confidence interval [CI] 0.380-0.960; P < 0.001). The areas under ROC curves (AUC) of pre-CBCT and contrast-enhanced CBCT were different: the AUC of pre-CBCT was 0.958 (P = 0.000, 95% CI 0.843-1.074), and the AUC of contrast-enhanced CBCT was 0.979 (P = 0.000, 95% CI 0.921-1.037), and the difference was not statistically significant (Z = - 0.707, P = 0.480). The ICC value of crack depth as measured by contrast-enhanced CBCT and micro-CT was 0.753 (95% CI 0.248-0.911; P < 0.001). CONCLUSION: Contrast-enhanced CBCT under vacuum conditions with a contrast medium can significantly improve the crack detection rate of cracked teeth; however, it cannot measure the crack depths accurately.

Transfer learning radiomics based on multimodal ultrasound imaging for staging liver fibrosis.

OBJECTIVES: To propose a transfer learning (TL) radiomics model that efficiently combines the information from gray scale and elastogram ultrasound images for accurate liver fibrosis grading. METHODS: Totally 466 patients undergoing partial hepatectomy were enrolled, including 401 with chronic hepatitis B and 65 without fibrosis pathologically. All patients received elastography and got liver stiffness measurement (LSM) 2-3 days before surgery. We proposed a deep convolutional neural network by TL to analyze images of gray scale modality (GM) and elastogram modality (EM). The TL process was used for liver fibrosis classification by Inception-V3 network which pretrained on ImageNet. The diagnostic performance of TL and non-TL was compared. The value of single modalities, including GM and EM alone, and multimodalities, including GM + LSM and GM + EM, was evaluated and compared with that of LSM and serological indexes. Receiver operating characteristic curve analysis was performed to calculate the optimal area under the curve (AUC) for classifying fibrosis of S4, ≥ S3, and ≥ S2. RESULTS: TL in GM and EM demonstrated higher diagnostic accuracy than non-TL, with significantly higher AUCs (all p < .01). Single-modal GM and EM both performed better than LSM and serum indexes (all p < .001). Multimodal GM + EM was the most accurate prediction model (AUCs are 0.950, 0.932, and 0.930 for classifying S4, ≥ S3, and ≥ S2, respectively) compared with GM + LSM, GM and EM alone, LSM, and biomarkers (all p < .05). CONCLUSIONS: Liver fibrosis can be staged by a transfer learning modal based on the combination of gray scale and elastogram ultrasound images, with excellent performance. KEY POINTS: • Transfer learning consists in applying to a specific deep learning algorithm that pretrained on another relevant problem, expected to reduce the risk of overfitting due to insufficient medical images. • Liver fibrosis can be staged by transfer learning radiomics with excellent performance. • The most accurate prediction model of transfer learning by Inception-V3 network is the combination of gray scale and elastogram ultrasound images.

Portal hypertension in hepatitis B-related cirrhosis: Diagnostic accuracy of liver and spleen stiffness by 2-D shear-wave elastography.

AIM: To assess the diagnostic accuracy of liver and spleen stiffness measured by 2-D shear-wave elastography (SWE) in evaluation of clinically significant and severe portal hypertension (CSPH and SPH, respectively). METHODS: Clinical data of 155 hepatitis B-related cirrhosis patients and their liver and spleen stiffness (L-SWE and S-SWE, respectively) were collected. The diagnostic performances of L-SWE, S-SWE, the liver stiffness-spleen diameter to platelet ratio score (LSPS) and portal hypertension risk score were evaluated. RESULTS: One hundred and four patients were eligible for analysis. Clinically significant and severe PH were detected in 84 and 74 patients, respectively. Liver and spleen stiffness were significantly correlated with hepatic venous pressure gradient in overall, CSPH, and SPH groups (rL = 0.607, 0.554, and 0.412; rS = 0.665, 0.566, and 0.467, respectively; all P < 0.05). The area under the receiver operating characteristic curves of L-SWE, S-SWE, LSPS, and PH risk score were 0.72 (95% confidence interval [CI], 0.49-0.95), 0.81 (95% CI, 0.55-0.97), 0.76 (95% CI, 0.51-0.96), and 0.73 (95% CI, 0.55-0.88) for CSPH, and 0.77 (95% CI, 0.51-0.93), 0.85 (95% CI, 0.59-0.96), 0.80 (95% CI, 0.58-0.98), and 0.80 (95% CI, 0.59-0.93) for SPH. The best cut-off of L-SWE for determining CSPH and SPH were 16.1 kPa (sensitivity, 78%; specificity, 72%) and 23.5 kPa (sensitivity, 81%; specificity, 79%). For S-SWE, the best cut-offs were 25.3 kPa (sensitivity, 85%; specificity, 79%) and 33.4 kPa (sensitivity, 74%; specificity, 70%). A cut-off of L-SWE <13.2 kPa or S-SWE <23.2 kPa was able to rule out CSPH, whereas a cut-off of L-SWE >24.9 kPa or S-SWE >34.2 kPa was able to rule in CSPH. CONCLUSIONS: Liver and spleen stiffness measured by 2-D SWE are reliable and promising non-invasive parameters to assess CSPH and SPH.

A Nude Mouse Model of Orthotopic Liver Transplantation of Human Hepatocellular Carcinoma HCCLM3 Cell Xenografts and the Use of Imaging to Evaluate Tumor Progression.

BACKGROUND This study aimed to develop a nude mouse model of orthotopic liver transplantation of HCCLM3 human hepatocellular carcinoma (HCC) cell xenografts and the use of imaging and histology to evaluate tumor development and progression. MATERIAL AND METHODS HCCLM3 cells were injected subcutaneously into 25 healthy male athymic BALB/c (nu/nu) nude mice. The tumors that developed were transplanted into the liver of a new set of nude mice. After four weeks and six weeks, the mice were imaged using ultrasound (US), software-assisted contrast-enhanced ultrasound (CEUS), fluorodeoxyglucose-positron emission tomography (FDG-PET). Histology was performed on the liver and liver tumors, and included immunohistochemistry for vascular endothelial growth factor (VEGF), CD31, CD34, and alpha-smooth muscle actin (alpha-SMA). RESULTS The success rate for orthotopic tumor transplantation in the mouse liver was 90% (18/20). Liver tumors measured 11.8±2.6 mm in diameter and 525.9±250.8 mm3 in volume on the sixth week. CEUS showed rapid wash-in and washout in the liver tumors, and PET showed low tumor cell metabolism. Bone metastases were present in 45% (9/20) of mice in the sixth week. Immunohistochemistry showed positive expression for VEGF, CD31, CD34, and alpha-SMA. CONCLUSIONS The nude mouse orthotopic liver transplantation model of human HCC was shown to be a reliable model that has the potential for future research on the pathogenesis and progression of HCC and studies on drug development.

Development of SNP, KASP, and SSR Markers by BSR-Seq Technology for Saturation of Genetic Linkage Map and Efficient Detection of Wheat Powdery Mildew Resistance Gene Pm61.

The gene Pm61 that confers powdery mildew resistance has been previously identified on chromosome arm 4AL in Chinese wheat landrace Xuxusanyuehuang (XXSYH). To facilitate the use of Pm61 in breeding practices, the bulked segregant analysis-RNA-Seq (BSR-Seq) analysis, in combination with the information on the Chinese Spring reference genome sequence, was performed in the F2:3 mapping population of XXSYH × Zhongzuo 9504. Two single nucleotide polymorphism (SNP), two Kompetitive Allele Specific PCR (KASP), and six simple sequence repeat (SSR) markers, together with previously identified polymorphic markers, saturated the genetic linkage map for Pm61, especially in the proximal side of the target gene that was short of gene-linked markers. In the newly established genetic linkage map, Pm61 was located in a 0.71 cM genetic interval and can be detected in a high throughput scale by the KASP markers Xicsk8 and Xicsk13 or by the standard PCR-based markers Xicscx497 and Xicsx538. The newly saturated genetic linkage map will be useful in molecular marker assisted-selection of Pm61 in breeding for disease resistant cultivar and in its map-based cloning.

Distribution of a phase-stabilized 100.02 GHz millimeter-wave signal over a 160 km optical fiber with 4.1 × 10-17 instability.

We report a long-distance phase-stabilized millimeter-wave distribution over optical fibers, where the optical-link-induced phase noise is compensated with a high-precision photonic-generated millimeter-wave (mm-wave) voltage-controlled oscillator (VCO). The mm-wave VCO is realized based on pre-filtering and re-modulating optical spectral lines of an optical frequency comb (OFC). By adjusting the frequency spacing of the optical spectral lines extracted from the OFC, the phase error of the transmitted optical mm-wave signal can be compensated precisely. Using the mm-wave VCO, we demonstrate a distribution of a 100.02 GHz signal over spooled optical fibers and the fractional frequency instability of the system at different transmission distances is exhibited. The residual phase noise of the remote mm-wave signal after being transferred through a 160-km fiber link is measured to be -59 dBc/Hz at 1 Hz frequency offset from the carrier, and the RMS timing jitter in the frequency range from 0.01 Hz to 1 MHz reaches 62 fs. The long-term fractional frequency instability of 4.1 × 10-17 at 10000 s averaging time is achieved, and the maximum timing drift is within 0.93 ps (peak to peak) during 4 hours.

Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis.

Gammaproteobacteria are important gut microbes but only persist at low levels in the healthy gut. The ecology of Gammaproteobacteria in the gut environment is poorly understood. Here, we demonstrate that choline is an important growth substrate for representatives of Gammaproteobacteria. Using Proteus mirabilis as a model, we investigate the role of choline metabolism and demonstrate that the cutC gene, encoding a choline-trimethylamine lyase, is essential for choline degradation to trimethylamine by targeted mutagenesis of cutC and subsequent complementation experiments. Proteus mirabilis can rapidly utilize choline to enhance growth rate and cell yield in broth culture. Importantly, choline also enhances swarming-associated colony expansion of P. mirabilis under anaerobic conditions on a solid surface. Comparative transcriptomics demonstrated that choline not only induces choline-trimethylamine lyase but also genes encoding shell proteins for the formation of bacterial microcompartments. Subsequent analyses by transmission electron microscopy confirmed the presence of such novel microcompartments in cells cultivated in liquid broth and hyper-flagellated swarmer cells from solid medium. Together, our study reveals choline metabolism as an adaptation strategy for P. mirabilis and contributes to better understand the ecology of this bacterium in health and disease.

Identification and characterization of trimethylamine N-oxide (TMAO) demethylase and TMAO permease in Methylocella silvestris†BL2.

Methylocella silvestris, an alphaproteobacterium isolated from a forest soil, can grow on trimethylamine N-oxide (TMAO) as a sole nitrogen source; however, the molecular and biochemical mechanisms underpinning its growth remain unknown. Marker-exchange mutagenesis enabled the identification of several genes involved in TMAO metabolism, including Msil_3606, a permease of the amino acids-polyamine (APC) superfamily, and Msil_3603, consisting of an N-terminal domain of unknown function (DUF1989) and a C-terminal tetrahydrofolate-binding domain. Null mutants of Msil_3603 and Msil_3606 can no longer grow on TMAO. Purified Msil_3603 from recombinant Escherichia coli can convert TMAO to dimethylamine and formaldehyde (1 TMAO → 1 dimethylamine + 1 formaldehyde), confirming that it encodes a bona fide TMAO demethylase (Tdm). Tdm of M. silvestris and eukaryotic Tdms have no sequence homology and contrasting characteristics. Recombinant Tdm of M. silvestris appears to be hexameric, has a high affinity for TMAO (Km = 3.3 mM; Vmax = 21.7 nmol min(-1) mg(-1) ) and only catalyses demethylation of TMAO and a structural homologue, dimethyldodecylamine N-oxide. Our study has contributed to the understanding of the genetic and biochemical mechanisms for TMAO degradation in M. silvestris.

Childhood trauma, psychache, and depression among university students: a moderated mediation model.

Background: Childhood trauma is a potential threat to depression and can have a lifelong impact on the mental health of university students. Our study aimed to construct a moderated mediation model to explore the relationship between childhood trauma, psychache, ambivalence over emotional expression, physical activity, and depression in university students. Methods: A cross-sectional study was conducted in three universities in China, recruiting 476 university students using self-report questionnaires. The moderated mediation model was examined using the SPSS PROCESS model 21. Results: Ambivalence over emotional expression (F=12.843), childhood trauma (F=117.639), and psychache (F=581.594) all had a significant positive effect on depression (p<0.001), explaining 2.9%, 21.7%, and 56.8% of the variance, respectively. On the chain of influence between childhood trauma and depression, the mediating effect of psychache, the moderating effect of ambivalence over emotional expression, and the moderating effect of physical activity are all significant the overall indirect effect value of the three is 0.287, accounting for 61.59% of the total effect. Conclusion: This study investigated the relationship between childhood trauma, ambivalence over emotional expression, psychache, physical activity, and depression in university students. Future interventions should focus on developing good emotional expression among university students, increasing opportunities for physical activity, and reducing psychache to reduce depression.

The protective effects of Ferrostatin-1 against inflammation-induced preterm birth and fetal brain injury.

INTRODUCTION: Recent studies have suggested the involvement of ferroptosis in preterm birth. Despite compelling evidence, the underlying mechanism remains unknown. This investigation aimed to determine the therapeutic effects of Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, in preterm birth and fetal brain injury. METHODS: Human placenta samples and clinical data of participants were collected to ascertain whether placental ferroptosis was associated with preterm birth. Lipopolysaccharide (LPS)-induced preterm birth mouse model was used to examine the protective effects of Fer-1 on preterm birth. Fetal brain tissues and offspring mice at 5 and 8 weeks were studied to determine the effects of Fer-1 on the cognitive function of offspring. RESULTS: We examined the mechanism of spontaneous preterm birth and discovered that placental ferroptosis was associated with preterm birth. Fer-1 inhibited preterm birth by ameliorating placental ferroptosis and maternal inflammation, thus improving LPS-induced intrauterine inflammation to maintain pregnancy. Antenatal administration of Fer-1 prevented LPS-induced fetal brain damage in the acute phase and improved long-term neurodevelopmental impairments by improving placental neuroendocrine signaling and maintaining placental function. CONCLUSION: Fer-1 inhibited preterm birth and fetal brain injury by inhibiting maternal inflammation and improving placental function. Our findings provide a novel therapeutic strategy for preterm birth.

The relationship between self-compassion, coping style, sleep quality, and depression among college students.

Background: The prevalence of sleep quality problems and depression in the college student population has attracted widespread attention. However, the factors influencing this are still unclear. The objective of this study was to investigate the associations between self-compassion (S-C), sleep quality (SQ), and depression (DEP) among college students and examine the mediating effects of coping style (CS) between the variables. Methods: A total of 1,038 Chinese university students were recruited for the study. The study used the Self-Compassion Scale (SCS), Simplified Coping Style Questionnaire (SCSQ), Depression Anxiety Stress Scale 21 (DASS-21), and Pittsburgh Sleep Quality Index (PSQI) to conduct the survey. Results: The self-compassion and coping style showed significant negative correlations with sleep quality and depression. Coping style partially mediated the relationship between self-compassion and sleep quality. The coping style also fully mediated the relationship between self-compassion and depression. Conclusion: This study reveals the associations between self-compassion and sleep quality and depression, and the mediating role of coping style among college students. This study provides valuable insights for improving sleep quality and alleviating depression problems among college students. It emphasizes the importance of self-compassion and positive coping style.

Analysis of potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression immunologic indicators.

OBJECTIVE: Depression can impact the severity of rheumatoid arthritis (RA). This study aimed to investigate the relationship between Th1, Th2, Th17, Treg cell subsets, and their associated cytokines (e.g., IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α), and the occurrence of RA both with and without comorbid depression. The objective is to identify potential biological markers, therapeutic targets, and the therapeutic effects of RA with comorbid depression. RESULTS: 53 RA patients,46 RA with comorbid depression patients and 51 healthy subjects were included in the RA,RD and HC group from August 2021 and October 2022. Among RA patients, 46.46 % were comorbid with depression. IL-6 concentrations were significantly higher in RD group than in RA group.Comparison between the HC and RA and RD groups revealed that Th1 %, Th17 %, Th1, Th17, Th1/Th2, Th17/Treg and Th1/Treg were significantly higher in the RA and RD groups, and conversely, Th2 %, Treg%, Th2 and Treg were significantly lower than in the HC group.The RA group compared to the RD group found that Th17 %, Th17 and Th17/Treg were significantly higher in the RD group than in the RA group, however, Th1 %, Treg and Th2/Treg were significantly lower than in the RA group. The total HAMD score had a medium strength positive correlation with IL-6. CONCLUSION: These findings suggest that elevated the autoimmunity status was overactivated in RA with or without depression activates patients, IL-6 may be a predictor of the severity of RA with comorbid depression, IL-6 concentrations and an imbalance in the Th17/Treg may underlie the comorbidity of RA and depression, offering potential targets for therapeutic intervention, prompting further evaluation of the role of indirect inflammatory markers in RA with comorbid depression, highlighting the need for additional research to clarify the complex relationship between inflammation and psychological health.

Targeting Mitochondrial Oxidative Stress to Protect Against Preterm Birth and Fetal Brain Injury via Nrf2 Induction.

Aims: Preterm birth (PTB), recognized as delivery before 37 weeks of gestation, is a multifactorial syndrome characterizing as the main cause of neonatal mortality. Reactive oxygen species (ROS) have been identified as proinflammatory factors to cause placental inflammation, thereby resulting in several pregnancy outcomes. To date, limited knowledge regarding the underlying mechanisms of ROS-induced PTB has been reported. In this study, we aimed to investigate the role of oxidative stress in PTB and the protective effects of mitochondria-targeted antioxidant MitoTEMPO (MT) on preterm labor and offspring mice. Results: In this study, we found that preterm placentas had abnormal mitochondrial function, oxidative stress, and inflammatory response. In the lipopolysaccharide (LPS)-induced PTB mouse model, MT inhibited PTB by ameliorating maternal oxidative stress and inflammation, especially in placentas, thus improving placental function to maintain pregnancy. Antenatal administration of MT prevented LPS-induced fetal brain damage in acute phase and improved long-term neurodevelopmental impairments. Furthermore, our in vitro investigations validated that MT retarded the ROS accumulation and inflammatory response in LPS-stimulated trophoblast cells by promoting Kelch-like ECH-associated protein 1 (Keap1) degradation and subsequently activating nuclear factor erythroid 2-related factor 2 (Nrf2). By inhibiting Nrf2 activation, we discovered that the anti-inflammation and protective characteristics of MT were Nrf2/ARE pathway dependent. Innovation and Conclusion: MT inhibited PTB and fetal brain injury by inhibiting maternal inflammation and improving placental function through Keap1/Nrf2/antioxidant response element signaling pathway. Our findings provide a novel therapeutic strategy for PTB.

Nitrogen migration and transformation during re-suspension and photo-induction in landscape water replenished by reclaimed water.

Sediment re-suspension plays a crucial role in releasing endogenous nitrogen and greenhouse gases in shallow urban waters. However, the impacts of repeated re-suspension and photo-induced processes on migration and transformation from endogenous nitrogen, as well as the emission of greenhouse gases, remain unclear. This study simulated three conditions: re-suspension (Rs), re-suspension combined with ultravioletirradiation (Rs + UV), and ultraviolet irradiation (UV). The findings revealed that both repeated sediment re-suspension and exposure to UV light altered the characteristics of surface sediments. Decrease of convertible nitrogen in sediments, leading to the release of ion-exchangeable nitrogen (IEF-N) into NH4+-N and NO3--N, influenced greenhouse gas production differently under various conditions. The study observed the highest concentration of dissolved N2O in under UV irradiation, positively correlated with NO2--N and NO3--N. Re-suspension increased the turbidity of the overlying water and accelerated nitrification, resulting in the highest NO3--N concentration and the lowest dissolved N2O concentration. Additionally, in the Rs + UV dissolved N2O maintained the higher concentrations than in Rs, with greatest amount of N conversion in surface sediments, and a 59.45% reduction in IEF-N. The production of N2O during re-suspension was mainly positively correlated with NH4+-N in the overlying water. Therefore, this study suggest that repeated re-suspension and light exposure significantly influence nitrogen migration and transformation processes in sediment, providing a theoretical explanation for the eutrophication of water and greenhouse gas emissions.

Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

Establishment of LC-MS/MS method for quantifying chlorpromazine metabolites with application to its metabolism in liver and placenta microsomes.

Chlorpromazine has sedative and antiemetic pharmacological effects and is widely used in clinic. Its main metabolites include 7-hydroxychlorpromazine, N-monodesmethylchlorpromazine and chlorpromazine sulfoxide, which affect the therapeutic efficacy. To support metabolism research, the quantitative analysis method of 7-hydroxychlorpromazine, N-monodesmethylchlorpromazine and chlorpromazine sulfoxide in microsomal enzymes was established for the first time by LC-MS/MS. This method has been fully validated in rat liver microsomes, and partially verified in human liver microsomes and human placenta microsomes. The intra-day and inter-day accuracy and precision of the analytes were all within ± 15%. The extraction recovery was good, and no matrix effect was detected. This accurate and sensitive method was successfully applied to chlorpromazine metabolism in different microsomal enzymes. In particular, the biotransformation of chlorpromazine in human placenta microsomes was detected for the first time. The metabolites detected in human liver and placenta microsomes presented different formation rates, indicating the wide distribution and different activities of drug-metabolizing enzymes.