Religious Practices and Spiritual Well-Being of Schizophrenia: Muslim Perspective.

Purpose: To explore religious activities and its functions on the spiritual wellbeing of Muslim patients with schizophrenia. Patients and Methods: Semi-structured in-depth interviews were conducted in six schizophrenia inpatients and two female nurses. Document analysis of the standard operating procedure related to patients' spiritual needs fulfilment and patients' medical records were also undertaken in order to triangulate data and to get insights about patient spiritual and religious activity. Thematic analysis was used to analyse data. Results: Five themes and 12 sub themes were revealed from the study data. The five themes elicited from the study namely frequency, timing, barriers to perform religious activities, impact on health status and negative effects if not performing the religious activities. Religious activities such as salat and dhikr for schizophrenia inpatients are still performed five times a day and when they are not getting period. Feeling upset, restless, happy, grateful, and when they are missing their family was the common reason why patients perform the religious activities. The main barriers to performing salat and dhikr for example: insufficient prayer tools and Al-Qur'an, as well as patients' physical conditions. Religious activities such as salat and dhikr positively impact patients' physical and mental health status, mindfulness, and concentration. Negative impacts physical and emotional are released when patients did not perform salat and dhikr. Conclusion: The findings show that salat and dhikr which perform on time and regularly have a positive impact on the physical and mental health of schizophrenia inpatients. The author might recommend the mental health hospital provide adequate worship or prayer equipment (gown and Al-Qur`an) for patients.

CAFrgDB: a database for cancer-associated fibroblasts related genes and their functions in cancer.

As one of the most essential components of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) interact extensively with cancer cells and other stromal cells to remodel TME and participate in the pathogenesis of cancer, which earmarked themselves as new promising targets for cancer therapy. Numerous studies have highlighted the heterogeneity and versatility of CAFs in most cancer types. Thus, the identification and appropriate use of CAF-related genes (CAFGenes) in the context of specific cancer types will provide critical insights into disease mechanisms and CAF-related therapeutic targets. In this study, we collected and curated 5421 CAFGenes identified from small- or large-scale experiments, encompassing 4982 responsors that directly or indirectly participate in cancer malignant behaviors managed by CAFs, 1069 secretions that are secreted by CAFs and 281 regulators that contribute in modulating CAFs in human and mouse, which covered 24 cancer types. For these human CAFGenes, we performed gene expression and prognostic marker-based analyses across 24 cancer types using TCGA data. Furthermore, we provided annotations for CAF-associated proteins by integrating the knowledge of protein-protein interaction(s), drug-target relations and basic annotations, from 9 public databases. CAFrgDB (CAF related Gene DataBase) is free for academic research at http://caf.zbiolab.cn and we anticipate CAFrgDB can be a useful resource for further study of CAFs.

Multi-Scale Feature Fusion Network for Low-Dose CT Denoising.

Computed tomography (CT) is an imaging technique extensively used in medical treatment, but too much radiation dose in a CT scan will cause harm to the human body. Decreasing the dose of radiation will result in increased noise and artifacts in the reconstructed image, blurring the internal tissue and edge details. To get high-quality CT images, we present a multi-scale feature fusion network (MSFLNet) for low-dose CT (LDCT) denoising. In our MSFLNet, we combined multiple feature extraction modules, effective noise reduction modules, and fusion modules constructed using the attention mechanism to construct a horizontally connected multi-scale structure as the overall architecture of the network, which is used to construct different levels of feature maps at all scales. We innovatively define a composite loss function composed of pixel-level loss based on MS-SSIM-L1 and edge-based edge loss for LDCT denoising. In short, our approach learns a rich set of features that combine contextual information from multiple scales while maintaining the spatial details of denoised CT images. Our laboratory results indicate that compared with the existing methods, the peak signal-to-noise ratio (PSNR) value of CT images of the AAPM dataset processed by the new model is 33.6490, and the structural similarity (SSIM) value is 0.9174, which also achieves good results on the Piglet dataset with different doses. The results also show that the method removes noise and artifacts while effectively preserving CT images' architecture and grain information.

Ferrous sulfate reverses cerebral metabolic abnormality induced by minimal hepatic encephalopathy.

Orally administered ferrous iron was previously reported to significantly improve the cognition and locomotion of patients with minimal hepatic encephalopathy (MHE). However, the metabolic mechanisms of the therapeutic effect of ferrous iron are unknown. In this study, MHE was induced in rats by partial portal vein ligation (PPVL), and was treated with ferrous sulfate. The Morris water maze was used to evaluate the cognitive condition of the rats. The metabolites observed by NMR and validated by liquid chromatography-mass spectrometry were defined as the key affected metabolites. The enzyme activities and trace element contents in the rat brains were also investigated. The Mn content was found to be increased but the ferrous iron content decreased in the cortex and striatum in MHE. Decreased oxoglutarate dehydrogenase activity and increased glutamine synthetase (GS) and pyruvate carboxylase (PC) activity were observed in the cortex of MHE rats. Decreased pyruvate dehydrogenase activity and increased GS and PC activity were observed in the striatum of MHE rats. The levels of BCAAs and taurine were significantly decreased, and the contents of GABA, lactate, arginine, aspartate, carnosine, citrulline, cysteine, glutamate, glutamine, glycine, methionine, ornithine, proline, threonine and tyrosine were significantly increased. These metabolic abnormalities described above were restored after treatment with ferrous sulfate. Pathway enrichment analysis suggested that urea cycle, aspartate metabolism, arginine and proline metabolism, glycine and serine metabolism, and glutamate metabolism were the major metabolic abnormalities in MHE rats, but these processes could be restored and cognitive impairment could be improved by ferrous sulfate administration.

Functional gradients in prefrontal regions and somatomotor networks reflect the effect of music training experience on cognitive aging.

Studies showed that the top-down control of the prefrontal cortex (PFC) on sensory/motor cortices changes during cognitive aging. Although music training has demonstrated efficacy on cognitive aging, its brain mechanism is still far from clear. Current music intervention studies have paid insufficient attention to the relationship between PFC and sensory regions. Functional gradient provides a new perspective that allows researchers to understand network spatial relationships, which helps study the mechanism of music training that affects cognitive aging. In this work, we estimated the functional gradients in four groups, young musicians, young control, older musicians, and older control. We found that cognitive aging leads to gradient compression. Compared with young subjects, older subjects presented lower and higher principal gradient scores in the right dorsal and medial prefrontal and the bilateral somatomotor regions, respectively. Meanwhile, by comparing older control and musicians, we found a mitigating effect of music training on gradient compression. Furthermore, we revealed that the connectivity transitions between prefrontal and somatomotor regions at short functional distances are a potential mechanism for music to intervene in cognitive aging. This work contributes to understanding the neuroplasticity of music training on cognitive aging.

Thrombus Enhancement Sign for Differentiation of Embolism and Arteriosclerosis-Related Acute Large Vessel Occlusion.

Background and Purpose: To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). Methods: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. Results: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4-53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8-15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. Conclusion TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Plant roots fuel tropical soil animal communities.

Belowground life relies on plant litter, while its linkage to living roots had long been understudied, and remains unknown in the tropics. Here, we analysed the response of 30 soil animal groups to root trenching and litter removal in rainforest and plantations in Sumatra, and found that roots are similarly important to soil fauna as litter. Trenching effects were stronger in soil than in litter, with an overall decrease in animal abundance in rainforest by 42% and in plantations by 30%. Litter removal little affected animals in soil, but decreased the total abundance by 60% in rainforest and rubber plantations but not in oil palm plantations. Litter and root effects on animal group abundances were explained by body size or vertical distribution. Our study quantifies principle carbon pathways in soil food webs under tropical land use, providing the basis for mechanistic modelling and ecosystem-friendly management of tropical soils.

Learnable spectral dimension compression mapping for full-band speech enhancement.

The highly imbalanced power spectral density of full-band speech signals poses a significant challenge to full-band speech enhancement, and the commonly used spectral features that mimic the behavior of the human auditory system are not an optimal choice for full-band speech enhancement. In this paper, a learnable spectral dimension compression mapping is proposed to effectively compress the spectral feature along frequency, preserving high resolution in low frequencies while compressing information in high frequencies in a more flexible manner. Experimental results verify that the proposed method can be easily combined with different full-band speech enhancement models and achieve better performance.

KRAS, NRAS, BRAF signatures, and MMR status in colorectal cancer patients in North China.

We assessed the clinicopathological features and prognostic values of KRAS, NRAS, BRAF, and DNA mismatch repair status in colorectal cancer (CRC) to provide real-world data in developing countries. We enrolled 369 CRC patients and analyzed the correlation between RAS/BRAF mutation, mismatch repair status with clinicopathological features, and their prognostic roles. The mutation frequencies of KRAS, NRAS, and BRAF were 41.7%, 1.6%, and 3.8%, respectively. KRAS mutations and deficient mismatch repair (dMMR) status were associated with right-sided tumors, aggressive biological behaviors, and poor differentiation. BRAF (V600E) mutations are associated with well-differentiated and lymphovascular invasion. The dMMR status predominated in young and middle-aged patients and tumor node metastasis stage II patients. dMMR status predicted longer overall survival in all CRC patients. KRAS mutations indicated inferior overall survival in patients with CRC stage IV. Our study showed that KRAS mutations and dMMR status could be applied to CRC patients with different clinicopathological features.

Nanocellulose interface enhanced all-cellulose foam with controllable strength via a facile liquid phase exchange route.

The development of sustainable, biodegradable, non-toxic biomass foams with outstanding physical properties to replace traditional petroleum-based foams is urgent. In this work, we proposed a simple, efficient, and scalable approach to fabricate nanocellulose (NC) interface enhanced all-cellulose foam through ethanol liquid phase exchange and subsequent ambient drying. In this process, NCs served as reinforcer and binder were integrated with pulp fiber to improve cellulose interfibrillar bonding and interface adhesion between NCs and pulp microfibrils. The resultant all-cellulose foam displayed stable microcellular structure (porosity of 91.7-94.5 %), low apparent density (0.08-0.12 g/cm3), and high compression modulus (0.49-2.96 MPa) by regulating the content and size of NCs. Further, the strengthening mechanism of the structure and property of all-cellulose foam were investigated in detail. This proposed process enabled ambient drying, and is simple and feasible for low-cost, practicable, and scalable production of biodegradable, green bio-based foam without special apparatuses and other chemicals.

Ultrasound-guided Jamshidi needle puncture to reduce radiation exposure during percutaneous pedicle screw placement: study protocol for a randomised controlled trial.

INTRODUCTION: Percutaneous pedicle screw placement (PPSP) is a minimally invasive procedure highly dependent on fluoroscopic guidance, which results in increased radiation exposure and prolonged operative time. Ultrasound can image the lumbar paravertebral anatomy and the needle trajectory in real time, which may help reduce the use of fluoroscopy and radiation dose in PPSP. We will conduct a parallel randomised controlled trial to mainly investigate the effect of ultrasound guidance in radiation reduction during PPSP. METHODS AND ANALYSIS: A total of 42 patients will be recruited and randomly assigned to the intervention group and the control group at a 1:1 ratio. In the intervention group, we will use ultrasound in combination with fluoroscopy to guide the insertion of the Jamshidi needles. In the control group, PPSP will be performed under conventional fluoroscopic guidance. The primary outcomes are the cumulative fluoroscopy time (s), radiation dose (mGy) and exposure times of screw placement. The secondary outcomes are insertion time of guidewire, rate of pedicle perforation, rate of facet joint violation, visual analogue scale for back pain, Oswestry Disability Index and complications. The participants, outcome assessors and data analysts will be blinded to allocation. ETHICS AND DISSEMINATION: The trial was approved by the research ethics committee of Shengjing Hospital, China Medical University. The results will be presented at academic seminars and submitted for publication in peer-reviewed journals.This study involves human participants and was approved by Research Ethics Committee of Shengjing Hospital, China Medical University reference number：2022PS704K. Participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION NUMBER: ChiCTR2200057131.

Pharmacokinetics and tissue distribution of bleomycin-induced idiopathic pulmonary fibrosis rats treated with cryptotanshinone.

Introduction: Cryptotanshinone(CTS), a compound derived from the root of Salvia miltiorrhiza, has been linked to various of diseases, particularly pulmonary fibrosis. In the current study, we investigated the benefit of CTS on Sprague-Dawley (SD) rats induced by bleomycin (BLM) and established high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods to compare pharmacokinetics and tissue distribution in subsequent normal and modulated SD rats. Methods: The therapeutic effect of CTS on BLM-induced SD rats was evaluated using histopathology, lung function and hydroxyproline content measurement, revealing that CTS significantly improved SD rats induced by BLM. Additionally, a simple, rapid, sensitive and specific HPLC-MS/MS method was developed to determine the pharmacokinetics of various components in rat plasma. Results: Pharmacokinetic studies indicated that CTS was slowly absorbed by oral administration and had low bioavailability and a slow clearance rate. The elimination of pulmonary fibrosis in 28-day rats was slowed down, and the area under the curve was increased compared to the control group. Long-term oral administration of CTS did not accumulate in vivo, but the clearance was slowed down, and the steady-state blood concentration was increased. The tissue distribution study revealed that CTS exposure in the lungs and liver. Discussion: The lung CTS exposure was significantly higher in the model group than in the control group, suggesting that the pathological changes of pulmonary fibrosis were conducive to the lung exposure of CTS and served as the target organ of CTS.

Brønsted acid-catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds.

In the past two decades, substantial advances have been made on the asymmetric alkyne functionalization by the activation of inert alkynes. However, these asymmetric transformations have so far been mostly limited to transition metal catalysis, and chiral Brønsted acid-catalyzed examples are rarely explored. Here, we report a chiral Brønsted acid-catalyzed dearomatization reaction of phenol- and indole-tethered homopropargyl amines, allowing the practical and atom-economical synthesis of a diverse array of valuable fused polycyclic enones and indolines bearing a chiral quaternary carbon stereocenter and two contiguous stereogenic centers in moderate to good yields with excellent diastereoselectivities and generally excellent enantioselectivities (up to >99% enantiomeric excess). This protocol demonstrates Brønsted acid-catalyzed asymmetric dearomatizations via vinylidene-quinone methides.

Coixol ameliorates Toxoplasma gondii infection-induced lung injury by interfering with T. gondii HSP70/TLR4/NF-κB signaling pathway.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo, respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti-T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii-derived heat shock protein 70 (T.g.HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g.HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g.HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.

RUNX1 together with DAT mutations predicted poor outcome in acute myeloid leukemia.

We retrospectively explored the prognostic impact of DAT mutations at diagnosis in 122 RUNX1mut AML patients. RUNX1 missense mutation was dominant in the RUNT domain, and frameshift mutation was dominant in the TAD domain. DAT mutations occurred in 38.5% of RUNX1mut AML. After propensity score matching, DATpos patients had worse two-year relapse-free survival (RFS) than DATneg patients (p = .041). Moreover, RUNX1high (VAF ≥ 37.6%) patients showed poorer two-year overall survival (OS) and RFS than RUNX1low (VAF < 37.6%) patients (OS, p = .033; RFS, p = .027), especially in the RUNX1highDATpos group. Additionally, multivariate analysis confirmed that DAT mutations at diagnosis were an independent adverse factor for RFS. There were no significant differences in two-year OS and RFS between DATpos and DATneg patients or between RUNX1high and RUNX1low patients who undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Collectively, DAT mutations at diagnosis were adverse factors for RFS, and allo-HSCT could likely improve the poor outcomes of these patients.

Study on Pharmacokinetics and Metabolic Profiles of Novel Potential PLK-1 Inhibitors by UHPLC-MS/MS Combined with UHPLC-Q-Orbitrap/HRMS.

PLK-1 (Polo-like kinase-1) plays an essential role in cytokinesis, and its aberrant expression is considered to be keenly associated with a wide range of cancers. It has been selected as an appealing target and small-molecule inhibitors have been developed and studied in clinical trials. Unfortunately, most have been declared as failures due to the poor therapeutic response and off-target toxicity. In the present study, a novel potent PLK-1 inhibitor, compound 7a, was designed and synthetized. 1H NMR, 13C NMR, 19F NMR and mass spectrum were comprehensively used for the compound characterization. The compound exhibited higher potency against PLK-1 kinase, HCT-116 and NCI-H2030 cell lines than the positive control. Molecular docking indicated that the binding mode that the ATP binding site of PLK-1 was occupied by the compound. Then, a UHPLC-MS/MS method was established and validated to explore the pharmacokinetic behavior of the drug candidate. The method had good selectivity, high sensitivity and wide linearity. The exposure increased linearly with the dose, but the oral bioavailability was not satisfactory enough. Then, the metabolism was studied using liver microsomes by UHPLC-Q-Orbitrap/HRMS. Our research first studied the pharmacokinetic metabolic characteristics of 7a and may serve as a novel lead compound for the development of PLK-1 inhibitors.

Ginsenoside Rb1 alleviated concanavalin A-induced hepatocyte pyroptosis by activating mitophagy.

Pyroptosis is characterized as gasdermin-mediated programmed death and has received substantial attention in recent years. Excessive hepatocyte pyroptosis could induce acute liver injury, and there is a lack of efficient natural compounds to alleviate it. Ginsenoside Rb1 is the most prevalent ginsenoside in ginseng with a variety of biological activities and is usually added to functional foods. In spite of the numerous beneficial effects ginsenoside Rb1 exerts, its role in hepatocyte pyroptosis is yet unknown. In this study, we found that ginsenoside Rb1 alleviated concanavalin A-induced hepatocyte pyroptosis and inhibited NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, which is critical for the process of pyroptosis. Furthermore, with the addition of the mitophagy inhibitor cyclosporin A, we proved that ginsenoside Rb1 promoted PINK1/Parkin-mediated mitophagy to alleviate hepatocyte pyroptosis. The further mechanism was that ginsenoside Rb1 activated mitophagy to eliminate damaged mitochondria. With the clearance of damaged mitochondria, reactive oxygen species production decreased, and then NLRP3 inflammasome expression was inhibited. Our finding demonstrated that ginsenoside Rb1 could alleviate hepatocyte pyroptosis by activating mitophagy, which could provide a basis for formulating effective dietary therapy or dietary recommendation.

Can left ventricular entropy by cardiac magnetic resonance late gadolinium enhancement be a prognostic predictor in patients with left ventricular non-compaction?

PURPOSE: Left ventricular non-compaction (LVNC) is considered rare; however, the use of cardiac magnetic resonance (CMR) has shown that its incidence is not uncommon, and its clinical presentation remains variable, with an uncertain prognosis. Risk stratification of major adverse cardiac events (MACE) in patients with LVNC remains complex. Therefore, this study aims to determine whether tissue heterogeneity from late gadolinium enhancement-derived entropy is associated with MACE in patients with LVNC. METHODS: This study was registered in the Clinical Trial Registry (CTR2200062045). Consecutive patients who underwent CMR imaging and were diagnosed with LVNC were followed up for MACE, which was defined by heart failure, arrhythmias, systemic embolism, and cardiac death. The patients were divided into MACE and non-MACE groups. The CMR parameters included left ventricular (LV) entropy, LV ejection fraction (LVEF), LV end-diastolic volume, LV end-systolic volume (LVESV), and LV mass (LVM). RESULTS: Eighty-six patients (age: 45.48 ± 16.64 years; female: 62.7%; LVEF: 42.58 ± 17.20%) were followed up for a median of 18 months and experienced 30 MACE events (34.9%). The MACE group showed higher LV entropy, LVESV, and LVM and lower LVEF than the non-MACE group. LV entropy [hazard ratio (HR): 1.710, 95% confidence interval (CI): 1.078-2.714, P = 0.023] and LVEF (HR: 0.961, 95% CI: 0.936-0.988, P = 0.004) were independent predictors of MACE (P <0.050) according to the Cox regression analysis. Receiver operating characteristic curve analysis revealed that the area under the curve of LV entropy was 0.789 (95% CI: 0.687-0.869, P < 0.001), LVEF was 0.804 (95% CI: 0.699-0.878, P < 0.001), and the combined model of LV entropy and LVEF was 0.845 (95% CI: 0.751-0.914, P < 0.050). CONCLUSION: LGE-derived LV entropy and LVEF are independent risk indicators of MACE in patients with LVNC. The combination of the two factors was more conducive to improving the prediction of MACE.