Decision-making under risk and its correlates in schizophrenia.

Schizophrenia spectrum disorders (SSD) are associated with pervasive cognitive impairments, including deficits in decision-making under risk. However, there is inconclusive evidence regarding specific mechanisms underlying altered decision-making patterns. In this study, participants (33 SSD and 28 non-SSD) completed the Columbia Card Task, an explicit risk-taking task, to better understand risk preference and adjustment in dynamic decision-making. We found that while there is no group difference in overall risk-taking, risk preference, or optimal decision-making, risk adjustment to contextual factors (e.g., loss probability) is blunted in SSD. We also found associations between risk-taking/suboptimal decision-making and disorganized symptoms, excited symptoms, and role functioning, but no associations between decision-making and working memory. These results suggest that during a complex, dynamic risk-taking task, individuals with SSD exhibit less adaption to changing information about risk, which may reflect risk imperception.

Enhancing gastric cancer early detection: A multi-verse optimized feature selection model with crossover-information feedback.

Gastric cancer (GC), an acknowledged malignant neoplasm, threatens life and digestive system functionality if not detected and addressed promptly in its nascent stages. The indispensability of early detection for GC to augment treatment efficacy and survival prospects forms the crux of this investigation. Our study introduces an innovative wrapper-based feature selection methodology, referred to as bCIFMVO-FKNN-FS, which integrates a crossover-information feedback multi-verse optimizer (CIFMVO) with the fuzzy k-nearest neighbors (FKNN) classifier. The primary goal of this initiative is to develop an advanced screening model designed to accelerate the identification of patients with early-stage GC. Initially, the capability of CIFMVO is validated through its application to the IEEE CEC benchmark functions, during which its optimization efficiency is measured against eleven cutting-edge algorithms across various dimensionalities-10, 30, 50, and 100. Subsequent application of the bCIFMVO-FKNN-FS model to the clinical data of 1632 individuals from Wenzhou Central Hospital-diagnosed with either early-stage GC or chronic gastritis-demonstrates the model's formidable predictive accuracy (83.395%) and sensitivity (87.538%). Concurrently, this investigation delineates age, gender, serum gastrin-17, serum pepsinogen I, and the serum pepsinogen I to serum pepsinogen II ratio as parameters significantly associated with early-stage GC. These insights not only validate the efficacy of our proposed model in the early screening of GC but also contribute substantively to the corpus of knowledge facilitating early diagnosis.

Plant-derived bioactive compounds and their novel role in central nervous system disorder treatment via ATF4 targeting: A systematic literature review.

Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aß, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.

EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.

The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/ß-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/ß-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib.

Novel insights into the activating transcription factor 4 in Alzheimer's disease and associated aging-related diseases: Mechanisms and therapeutic implications.

Ageing is inherent to all human beings, most mechanistic explanations of ageing results from the combined effects of various physiological and pathological processes. Additionally, aging pivotally contributes to several chronic diseases. Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding protein family, has recently emerged as a pivotal player owing to its indispensable role in the pathophysiological processes of Alzheimer's disease and aging-related diseases. Moreover, ATF4 is integral to numerous biological processes. Therefore, this article aims to comprehensively review relevant research on the role of ATF4 in the onset and progression of aging-related diseases, elucidating its potential mechanisms and therapeutic approaches. Our objective is to furnish scientific evidence for the early identification of risk factors in aging-related diseases and pave the way for new research directions for their treatment. By elucidating the signaling pathway network of ATF4 in aging-related diseases, we aspire to gain a profound understanding of the molecular and cellular mechanisms, offering novel strategies for addressing aging and developing related therapeutics.

Nontarget Identification of Novel Organophosphorus Flame Retardants and Plasticizers in Indoor Air and Dust from Multiple Microenvironments in China.

The indoor environment is a typical source for organophosphorus flame retardants and plasticizers (OPFRs), yet the source characteristics of OPFRs in different microenvironments remain less clear. This study collected 109 indoor air samples and 34 paired indoor dust samples from 4 typical microenvironments within a university in Tianjin, China, including the dormitory, office, library, and information center. 29 target OPFRs were analyzed, and novel organophosphorus compounds (NOPs) were identified by fragment-based nontarget analysis. Target OPFRs exhibited the highest air and dust concentrations of 46.2-234 ng/m3 and 20.4-76.0 µg/g, respectively, in the information center, where chlorinated OPFRs were dominant. Triphenyl phosphate (TPHP) was the primary OPFR in office air, while tris(2-chloroethyl) phosphate dominated in the dust. TPHP was predominant in the library. Triethyl phosphate (TEP) was ubiquitous in the dormitory, and tris(2-butoxyethyl) phosphate was particularly high in the dust. 9 of 25 NOPs were identified for the first time, mainly from the information center and office, such as bis(chloropropyl) 2,3-dichloropropyl phosphate. Diphenyl phosphinic acid, two hydroxylated and methylated metabolites of tris(2,4-ditert-butylphenyl) phosphite (AO168), and a dimer phosphate were newly reported in the indoor environment. NOPs were widely associated with target OPFRs, and their human exposure risk and environmental behaviors warrant further study.

impHFrEF trial: study protocol for an open-label, multicentre study of improvement the outcome of patients with heart failure in China using a mobile hEalth-supported platForm.

BACKGROUND: Patients with chronic heart failure (CHF) often have a long duration of illness, difficulty in attending follow-up visits, and poor adherence to treatment. As a result, they frequently cannot receive guideline-directed medical therapy (GDMT) at the desired or maximum tolerable drug dosage. This leads to high hospitalisation and mortality rates for HF patients. Therefore, effective management and monitoring of patients with HF to ensure they receive GDMT is crucial for improving the prognosis. DESIGN AND METHODS: This is a multicentre, open-label, randomised, parallel-group study involving patients with CHF across five centres. The study aims to assess the impact of an optimised GDMT model for HF patients, established on a mobile health (mHealth) platform, compared with a control group. Patients must have a left ventricular ejection fraction of less than 50% and be receiving medication titration therapy that has not yet reached the target dose, with a modest increase in N-terminal pro-B-type natriuretic peptide level. The primary composite outcome is worsening HF events (hospitalisation or emergency treatment with intravenous fluids) or cardiovascular death. ETHICS AND DISSEMINATION: On 22 December 2021, this study received ethical approval from the Ethics Review Board of the First Affiliated Hospital of Nanjing Medical University, with the ethics number 2021-SR-530. All study participants will be informed of the research purpose and their participation will be voluntary. Informed consent will be obtained by providing and signing an informed consent form. We will ensure compliance with relevant laws and regulations regarding privacy and data protection. The results of this study will be published in a peer-reviewed academic journal. We will ensure that the dissemination of study results is accurate, clear and timely. TRIAL REGISTRATION NUMBER: ChiCTR2200056527.

Irreversible Transmural Intestinal Necrosis in Acute Mesenteric Ischemia: Retrospective Cohort Study from a High-Volume Hospital.

Background: Owing to the low incidence rate and nonspecific symptoms of acute mesenteric ischemia (AMI), the identification and prediction of irreversible transmural intestinal necrosis (ITIN) and extensive bowel resection (≥100 cm) (EBR) are difficult and critical. This study aimed to investigate the risk factors for ITIN and EBR in patients with AMI. Methods: The clinical data of 254 AMI patients were retrospectively analyzed. Furthermore, the incidence of ITIN and EBR were set as dependent variables, and relevant risk factors were screened using univariate and multivariate logistic regression analyses. The comparisons of surgical characteristics and postoperative recovery outcomes between the EBR and control group were also conducted. Results: The presence of hemorrhagic (odds ratio [OR] = 28.356, P < .001) or other types ascites (OR = 13.051, P = .003), peritonitis (OR = 8.463, P = .005), intestinal diameter >2.35 cm (OR = 5.493, P = .020), and serum creatinine (CREA) >95 µmol/L (OR = 4.866, P = .048) were identified as independent risk factors for ITIN in patients with AMI. In addition, serum C-reactive protein (CRP) >15 mg/L (OR = 38.023, P = .006), and CREA >100 µmol/L (OR = 6.248, P = .035) were proved to be independently associated with EBR for ITIN cases. Compared to the control group, EBR significantly increased the likelihood of requiring enterostomy (P = .001), blood transfusion (P = .002), and transfer to intensive care unit (P = .016), while also prolonging the recovery time for intestinal function (P = .014). Conclusions: The presence of ascites, peritonitis, intestinal diameter >2.35 cm, and serum CREA >95 µmol/L were independently correlated with ITIN for AMI cases, while serum CRP >15 mg/L and CREA >100 µmol/L independently increased the risk of EBR.

Nomograms integrating the collagen signature and systemic immune-inflammation index for predicting prognosis in rectal cancer patients.

BACKGROUND: This study aimed to develop and validate a model based on the collagen signature and systemic immune-inflammation index to predict prognosis in rectal cancer patients who underwent neoadjuvant treatment. METHODS: Patients with rectal cancer who had residual disease after neoadjuvant treatment at two Chinese institutions between 2010 and 2018 were selected, one used as a training cohort and the other as a validation cohort. In total, 142 fully quantitative collagen features were extracted using multiphoton imaging, and a collagen signature was generated by least absolute shrinkage and selection operator Cox regression. Nomograms were developed by multivariable Cox regression. The performance of the nomograms was assessed via calibration, discrimination and clinical usefulness. The outcomes of interest were overall survival and disease-free survival calculated at 1, 2 and 3 years. RESULTS: Of 559 eligible patients, 421 were selected (238 for the training cohort and 183 for the validation cohort). The eight-collagen-features collagen signature was built and multivariable Cox analysis demonstrated that it was an independent prognostic factor of prognosis along with the systemic immune-inflammation index, lymph node status after neoadjuvant treatment stage and tumour regression grade. Then, two nomograms that included the four predictors were computed for disease-free survival and overall survival. The nomograms showed satisfactory discrimination and calibration with a C-index of 0.792 for disease-free survival and 0.788 for overall survival in the training cohort and 0.793 for disease-free survival and 0.802 for overall survival in the validation cohort. Decision curve analysis revealed that the nomograms could add more net benefit than the traditional clinical-pathological variables. CONCLUSIONS: The study found that the collagen signature, systemic immune-inflammation index and nomograms were significantly associated with prognosis.

Bovine parainfluenza virus type 3 infections induce ER stress-mediated autophagy to facilitate virus replication.

Bovine Parainfluenza Virus Type 3 (BPIV3) serves as a crucial pathogen in cattle, adept at triggering severe respiratory symptoms. This investigation explores the intricate interplay of endoplasmic reticulum stress (ER stress), unfolded protein response (UPR), and autophagy upon BPIV3 infection. In this study, we initially confirm a substantial increase in glucose regulatory protein 78 (GRP78) expression, accompanied by noticeable morphological changes and significant expansion of the ER lumen observed through transmission electron microscopy upon BPIV3 infection. Our findings indicate that ER Stress is induced during BPIV3 infection in vitro. Subsequently, we illustrate that BPIV3 triggers ER Stress to facilitate viral replication through heightened autophagy through treatment with the ER stress inhibitor 4-phenylbutyrate (4-PBA) and utilizing small interfering RNA (siRNA) technology to knock down GRP78. Additionally, we observe that the activation of ER stress initiates the UPR via PERK and ATF6 pathways, with the IRE1 pathway not contributing to the regulation of ER stress-mediated autophagy. Moreover, intervention with the PERK inhibitor GSK2606414, ATF6 inhibitor Ceapin-A7, and siRNA technology successfully reverses BPIV3-induced autophagy. In summary, these findings propose that BPIV3 induces ER stress to enhance viral replication through increased autophagy, with the PERK and ATF6 pathways playing a significant role in ER stress-mediated autophagy.

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Asymmetrical Interactions between Ni Single Atomic Sites and Ni Clusters in a 3D Porous Organic Framework for Enhanced CO2 Photoreduction.

3D porous organic frameworks, which possess the advantages of high surface area and abundant exposed active sites, are considered ideal platforms to accommodate single atoms (SAs) and metal nanoclusters (NCs) in high-performance catalysts; however, very little research has been conducted in this field. In the present work, a 3D porous organic framework containing Ni1 SAs and Nin NCs is prepared through the metal-assisted one-pot polycondensation of tetraaldehyde and hexaaminotriptycene. The single metal sites and metal clusters confined in the 3D space created a favorable micro-environment that facilitated the activation of chemically inert CO2 molecules, thus promoting the overall photoconversion efficiency and selectivity of CO2 reduction. The 3D-NiSAs/NiNCs-POPs, as a CO2 photoreduction catalyst, demonstrated an exceptional CO production rate of 6.24 mmol g-1  h-1 , high selectivity of 98%, and excellent stability. The theoretical calculations uncovered that asymmetrical interaction between Ni1 SAs and Nin NCs not only favored the bending of CO2 molecules and reducing the CO2 reduction energy, but also regulated the electronic structure of the catalyst leading to the optimal binding strength of intermediates.

CHL1 inhibits cell proliferation, migration and invasion by regulating the NF­κB signaling pathway in colorectal cancer.

Cell adhesion molecule close homolog of L1 (CHL1) is implicated in tumorigenesis of various malignancies. However, its role and underlying molecular mechanisms in colorectal cancer (CRC) remain unclear. The present study aimed to evaluate the specific biological functions and mechanisms of CHL1, in order to provide a theoretical basis for the use of CHL1 as a biological target in CRC. CHL1 expression was originally determined in CRC cell lines. Subsequently, CHL1 overexpression was induced by plasmid transfection in HT29 and SW480 cells, and cell proliferation, migration and invasion were evaluated using the Cell Counting Kit-8, clone formation, organoids formation and Transwell assays. Immunofluorescence and western blotting were performed to assess the protein expression of E-cadherin or N-cadherin. Differentially expressed genes (DEGs) were further evaluated using RNA-sequencing (RNA-seq) in HT29 and SW480 cells following CHL1 overexpression and functional enrichment analysis. Western blotting was performed to validate the expression of proteins related to the nuclear factor κB (NF-κB) signaling pathway. The TNMplot online database revealed the significant downregulation of CHL1 in CRC tissues. The results indicated that exogenous CHL1 overexpression significantly inhibited the proliferative, organoid-forming, migratory and invasive abilities of HT29 and SW480 cells, and increased E-cadherin protein expression. Additionally, CHL1 overexpression reduced xenograft tumor growth in vivo. RNA-seq and functional analysis revealed that DEGs in CHL1 overexpressing cells were mainly enriched in the NF-κB signaling pathway. The expression of p-p65 and p-p65/p65 ratio were significantly reduced in HT29 and SW480 cells, following CHL1 overexpression. Additionally, the inhibitory effects of CHL1 overexpression on CRC cell proliferation, organoid formation, migration and invasion were partially counteracted following the overexpression of p65 expression. Overall, the present study demonstrates that CHL1 inhibits CRC cell growth, migration and invasion through the inactivation of the NF-κB signaling pathway.

Emission characteristics of pulse CNT cold cathode X-ray source combined with channel electron multiplier.

Carbon nanotube (CNT)-based field emission X-ray source with the advantage of fast start-up response offers the chance to achieve high-frequency X-ray emission. In this study, a high-frequency random pulse X-ray source of CNT cold cathode combined with a channel electron multiplier (CEM) was built, and its direct current (DC) and pulse emission characteristics were tested. The DC measurement results were used for parameter selection for performing pulse experiments. During the DC test, with the conditions of 2.2 kV CEM bias voltage and 25 kV anode voltage, the anode currents are 141, 250, and 300 µA at grid voltages of 290, 387.6, and 432.2 V, respectively; the corresponding grid field values are 1.45, 1.94, and 2.16 V/µm. During the pulse test, the amplitude-frequency response of the X-ray source reaches 3.58 MHz at 3 dB. The developed pulse X-ray source was introduced into the X-ray communication (XCOM), and the experimental communication rate reached 6 Mbps with the bit-error-rate of 1.1 × 10-3. The developed high-frequency pulse CNT-CEM X-ray source has potential applications in XCOM, high-speed X-ray imaging, and other fields.

Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

Mn-Co-Ce/biochar based particles electrodes for removal of COD from coking wastewater by 3D/HEFL system: Characteristics, optimization, and mechanism.

In this work, the Mn, Co, Ce co-doped corn cob biochar (MCCBC) as catalytic particle electrodes in a three-dimensional heterogeneous electro-Fenton-like (3D-HEFL) system for the efficient degradation of coking wastewater was investigated. Various characterization methods such as SEM, EDS, XRD, XPS and electrochemical analysis were employed for the prepared materials. The results showed that the MCCBC particle electrodes had excellent electrochemical degradation performances of COD in coking wastewater, and the COD removal and degradation rates of the 3D/HEFL system were 85.35% and 0.0563 min-1 respectively. RSM optimized conditions revealed higher COD removal rate at 89.23% after 31.6 min of electrolysis. The efficient degradability and wide adaptability of the 3D/HEFL system were due to its beneficial coupling mechanism, including the synergistic effect between the system factors (3D and HEFL) as well as the synergistic interactions between the ROS (dominated by •OH and supplemented by O2•-) in the system. Moreover, the COD removal rate of MCCBC could still remain at 81.41% after 5 cycles with a lower ion leaching and a specific energy consumption of 11.28 kWh kg-1 COD. The superior performance of MCCBC, as catalytic particle electrodes showed a great potential for engineering applications for the advanced treatment of coking wastewater.

Association of antenatal corticosteroids with mortality and morbidities in very preterm infants born to women with hypertensive disorders of pregnancy: a multicenter prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.

Pathomics Signature for Prognosis and Chemotherapy Benefits in Stage III Colon Cancer.

Importance: The current TNM staging system may not provide adequate information for prognostic purposes and to assess the potential benefits of chemotherapy for patients with stage III colon cancer. Objective: To develop and validate a pathomics signature to estimate prognosis and benefit from chemotherapy using hematoxylin-eosin (H-E)-stained slides. Design, Setting, and Participants: This retrospective prognostic study used data from consecutive patients with histologically confirmed stage III colon cancer at 2 medical centers between January 2012 and December 2015. A total of 114 pathomics features were extracted from digital H-E-stained images from Nanfang Hospital of Southern Medical University, Guangzhou, China, and a pathomics signature was constructed using a least absolute shrinkage and selection operator Cox regression model in the training cohort. The associations of the pathomics signature with disease-free survival (DFS) and overall survival (OS) were evaluated. Patients at the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, formed the validation cohort. Data analysis was conducted from September 2022 to March 2023. Main Outcomes and Measures: The prognostic accuracy of the pathomics signature as well as its association with chemotherapy response were evaluated. Results: This study included 785 patients (mean [SD] age, 62.7 [11.1] years; 437 [55.7%] male). A pathomics signature was constructed based on 4 features. Multivariable analysis revealed that the pathomics signature was an independent factor associated with DFS (hazard ratio [HR], 2.46 [95% CI, 2.89-4.13]; P < .001) and OS (HR, 2.78 [95% CI, 2.34-3.31]; P < .001) in the training cohort. Incorporating the pathomics signature into pathomics nomograms resulted in better performance for the estimation of prognosis than the traditional model in a concordance index comparison in the training cohort (DFS: HR, 0.88 [95% CI, 0.86-0.89] vs HR, 0.73 [95% CI, 0.71-0.75]; P < .001; OS: HR, 0.85 [95% CI, 0.84-0.86] vs HR, 0.74 [95% CI, 0.72-0.76]; P < .001) and validation cohort (DFS: HR, 0.83 [95% CI, 0.82-0.85] vs HR, 0.70 [95% CI, 0.67-0.72]; P < .001; OS: HR, 0.80 [95% CI, 0.78-0.82] vs HR, 0.69 [0.67-0.72]; P < .001). Further analysis revealed that patients with a low pathomics signature were more likely to benefit from chemotherapy (eg, combined cohort: DFS: HR, 0.44 [95% CI, 0.28-0.69]; P = .001; OS: HR, 0.43 [95% CI, 0.29-0.64]; P < .001). Conclusions and Relevance: These findings suggest that a pathomics signature could help identify patients most likely to benefit from chemotherapy in stage III colon cancer.

Bovine parainfluenza type 3 virus induces incomplete autophagy to promote viral replication by activated beclin1 in vitro.

Bovine Parainfluenza virus Type 3 (BPIV3) is one of the most important pathogens in cattle, capable of causing severe respiratory symptoms. Numerous studies have shown that autophagy plays a diverse role in the infection process of various pathogens. The influence of autophagy machinery on BPIV3 infection has not yet been confirmed. In the present study, we initially demonstrated that the expression of LC3 was significantly increased and exhibited a notable increase in double or single-membrane vesicles under a transmission electron microscope during BPIV3 infection. These observations unequivocally establish the induction of steady-state autophagy in vitro consequent to BPIV3 infection. Furthermore, quantification of autophagic flux substantiates the induction of an incomplete autophagic process during BPIV3 infection. Additionally, through targeted interventions, we demonstrate the regulatory impact of pharmacological agents influencing autophagy and RNA interference targeting an autophagy-associated protein on viral replication. Intriguingly, our data revealed that BPIV3 infection enhanced the phosphorylation of rapamycin kinase (mTOR). This result demonstrated that mTOR does not operate as a counteractive regulator of BPIV3-induced autophagy. Instead, we discern an augmentation in the expression of Beclin1, a key autophagy initiator, which complexes with Vps34, constituting a Class III phosphatidylinositol 3-kinase. This phenomenon serves as a hallmark in the inaugural phase of autophagy initiation during BPIV3 infection. Collectively, these discernments underscore that BPIV3 infection actively stimulates autophagy, thereby enhancing viral replication through the activation of Beclin1, independently of the mTOR signaling pathway. This nuanced comprehension significantly contributes to unraveling the intricate molecular mechanisms governing BPIV3-induced autophagy.