Rapid and scalable photocatalytic C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling of aryl bromides with alkyl boranes.

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki-Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

Bayesian modelling of time series data (BayModTS) - a FAIR workflow to process sparse and highly variable data.

MOTIVATION: Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilise such information while consistently handling uncertainties. RESULTS: We present BayModTS (Bayesian Modelling of Time Series data), a new FAIR (Findable, Accessible, Interoperable and Reusable) workflow for processing and analysing sparse and highly variable time series data. BayModTS consistently transfers uncertainties from data to model predictions, including process knowledge via parameterised models. Further, credible differences in the dynamics of different conditions can be identified by filtering noise. To demonstrate the power and versatility of BayModTS, we applied it to three hepatic datasets gathered from three different species and with different measurement techniques: (i) blood perfusion measurements by magnetic resonance imaging in rat livers after portal vein ligation, (ii) pharmacokinetic time series of different drugs in normal and steatotic mice, and (iii) CT-based volumetric assessment of human liver remnants after clinical liver resection. AVAILABILITY AND IMPLEMENTATION: The BayModTS codebase is available on GitHub at https://github.com/Systems-Theory-in-Systems-Biology/BayModTS. The repository contains a Python script for the executable BayModTS workflow and a widely applicable SBML (Systems Biology Markup Language) model for retarded transient functions. In addition, all examples from the paper are included in the repository. Data and code of the application examples are stored on DaRUS https://doi.org/10.18419/darus-3876. The raw MRI ROI voxel data were uploaded to DaRUS https://doi.org/10.18419/darus-3878. The steatosis metabolite data are published on FairdomHub 10.15490/fairdomhub.1.study.1070.1.

Longitudinal NT-proBNP: Associations With Echocardiographic Changes and Outcomes in Heart Failure.

BACKGROUND: The relationship of serial NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements with changes in cardiac features and outcomes in heart failure (HF) remains incompletely understood. We determined whether common clinical covariates impact these relationships. METHODS AND RESULTS: In 2 nationwide observational populations with HF, the relationship of serial NT-proBNP measurements with serial echocardiographic parameters and outcomes was analyzed, further stratified by HF with reduced versus preserved left ventricular ejection fraction, inpatient versus outpatient enrollment, age, obesity, chronic kidney disease, atrial fibrillation, and attainment of ≥50% guideline-recommended doses of renin-angiotensin system inhibitors and ß-blockers. Among 1911 patients (mean±SD age, 65.1±13.4 years; 26.6% women; 62% inpatient and 38% outpatient), NT-proBNP declined overall, with more rapid declines among inpatients, those with obesity, those with atrial fibrillation, and those attaining ≥50% guideline-recommended doses. Each doubling of NT-proBNP was associated with increases in left ventricular volume (by 6.1 mL), E/e' (transmitral to mitral annular early diastolic velocity ratio) (by 1.4 points), left atrial volume (by 3.6 mL), and reduced left ventricular ejection fraction (by -2.1%). The effect sizes of these associations were lower among patients with HF with preserved ejection fraction, atrial fibrillation, or advanced age (Pinteraction<0.001). A landmark analysis identified that an SD increase in NT-proBNP over 6 months was associated with a 27% increase in the risk of the composite event of HF hospitalization or all-cause death between 6 months and 2 years (adjusted hazard ratio, 1.27 [95% CI, 1.15-1.40]; P<0.001). CONCLUSIONS: The relationships between NT-proBNP and structural/functional remodeling differed by age, presence of atrial fibrillation, and HF phenotypes. The association of increased NT-proBNP with increased risk of adverse outcomes was consistent in all subgroups.

Targeting the Cdc2-like kinase 2 for overcoming platinum resistance in ovarian cancer.

Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2-like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum-free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum-induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP-ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient-derived xenografts, especially those with wild-type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.

On-Chip Broadband, Compact TM Mode Mach-Zehnder Optical Isolator Based on InP-on-Insulator Platforms.

An integrated optical isolator is a crucial part of photonic integrated circuits (PICs). Existing optical isolators, predominantly based on the silicon-on-insulator (SOI) platform, face challenges in integrating with active devices. We propose a broadband, compact TM mode Mach-Zehnder optical isolator based on InP-on-insulator platforms. We designed two distinct magneto-optical waveguide structures, employing different methods for bonding Ce:YIG and InP, namely O2 plasma surface activation direct wafer bonding and DVS-benzocyclobutene (BCB) adhesive bonding. Detailed calculations and optimizations were conducted to enhance their non-reciprocal phase shift (NRPS). At a wavelength of 1550 nm, the direct-bonded waveguide structure achieved a 30 dB bandwidth of 72 nm with a length difference of 0.256 µm. The effects of waveguide arm length, fabrication accuracy, and dimensional errors on the device performance are discussed. Additionally, manufacturing tolerances for three types of lithographic processes were calculated, serving as references for practical manufacturing purposes.

Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study.

BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

Biological Activities of Deer Antler-Derived Peptides on Human Chondrocyte and Bone Metabolism.

Orally administered "tortoiseshell and deer antler gelatin" is a common traditional medicine for patients with osteoporosis or osteoarthritis. From the pepsin-digested gelatin, we previously isolated and identified the osteoblast-stimulating pentapeptide, TSKYR. Its trypsin digestion products include the dipeptide YR, enhancing calcium ion uptake, and tripeptide TSK, resulting in remarkable 30- and 50-fold increases in mineralized nodule area and density in human osteoblast cells. These peptides were chemically synthesized in this study. The composition of deer antler preparations comprises not only proteins and peptides but also a significant quantity of metal ion salts. By analyzing osteoblast growth in the presence of peptide YR and various metal ions, we observed a synergistic effect of calcium and strontium on the effects of YR. Those peptides could also stimulate the growth of C2C12 skeletal muscle cells and human chondrocytes, increasing collagen and glycosaminoglycan content in a three-dimensional environment. The maintenance of bone homeostasis relies on a balance between osteoclasts and osteoblasts. Deer antler peptides were observed to inhibit osteoclast differentiation, as evidenced by ROS generation, tartrate-resistant acid phosphatase (TRACP) activity assays, and gene expression in RAW264.7 cells. In summary, our findings provide a deep understanding of the efficacy of this folk medicine.

Thresholds in PROMIS Scores Anchored to Subsequent Unscheduled Health Service Use Among People Diagnosed With Cancer.

PURPOSE: To establish thresholds in the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference, physical function, fatigue, and depression scores on the basis of their association with subsequent use of the emergency department (ED) or urgent care by people diagnosed with cancer. METHODS: Retrospective data from 952 people seen at Henry Ford Cancer and insured through the Health Alliance Plan were analyzed using generalized linear mixed-effects models. The log odds of ED or urgent care use during 14 or 30 days after each patient-reported outcome (PRO) assessment were related to PRO scores, while adjusting for comorbidity, sociodemographic, and tumor characteristics. RESULTS: Pain interference and physical function were associated with subsequent ED or urgent care visits, but fatigue and depression were not, and the results for 14- and 30-day visits were similar. Thresholds anchored in the likelihood of these visits differed according to cancer stage. For people with advanced cancer, a pain interference score of 60 or higher (odds ratio [OR] 3.75, [95% CI, 1.53 to 7.87]) and a physical function score lower than 40 (OR 2.94, [95% CI, 1.22 to 7.06]) produced the largest ORs with narrowest CIs for 30-day visits. For people with nonadvanced cancer, the thresholds of 65 for pain interference (OR 2.64, [95% CI, 1.40 to 5.01]) and 35 for physical function (OR 1.87, [95% CI, 1.01 to 3.45]) produced largest ORs with narrowest CIs for 30-day visits. CONCLUSION: These anchor-based thresholds in PROMIS scores can inform clinicians' actions with the goal of preventing ED or urgent care visits.

Feasibility of 18F-DOPA and 18F-FDG PET/CT for guiding decision-making for localized incidental neuroblastoma in infants under 18 months of age.

BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.

Oleanane and 30-noroleanane triterpenoids from the roots of Paeonia lactiflora.

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.

Association between self-efficacy, spiritual well-being and the willingness to provide spiritual care among nursing staff in Taiwan: a cross-sectional study.

BACKGROUND: Spiritual care plays a significant role in holistic patient care, addressing not only physical ailments but also attending to patients' emotional and spiritual well-being. While the importance of spiritual care in nursing is widely recognized, there is often a gap in understanding nurses' willingness to provide such care. This cross-sectional study aimed to explore the association between self-efficacy, spiritual well-being, and willingness to provide spiritual care among nursing staff. METHODS: The study conducted a cross-sectional survey of full-time registered nurses at a hospital in Taiwan from January 2019 to December 2019. A sample comprising 168 nurses was selected for participation in the study through a random sampling method. In addition to collecting demographic variables, the assessment tools used in the study include the General Self-Efficacy Scale (GSES) for measuring self-efficacy, the Spiritual Index of Well-Being Chinese Version (SIWB-C) for evaluating spiritual well-being, and the Spiritual Care Needs Inventory (SCNI) to gauge willingness to provide spiritual care. RESULTS: Most participants in the study were female, accounting for 98.2% (n = 165). The mean age of all 168 nurses was 37.1 ± 9.3 years. Additionally, most participants held a Bachelor's degree (79.2%, n = 133) and possessed clinical experience was 10.5 ± 9.3 years. Through logistic regression analysis, it was found that regardless of whether participants have received sufficient spiritual care training, both GSES and SIWB-C remain influential factors in determining the provision of spiritual care. CONCLUSIONS: Collaboration between healthcare management and nursing staff is essential for fostering a healthcare environment that not only appreciates the physical and spiritual dimensions of patient care but also prioritizes the enhancement of nurses ' self-efficacy and well-being.

Altered cortical thickness and structural covariance networks in chronic low back pain.

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013-2014 National Health and Nutrition Examination Survey.

Organophosphate flame retardants (OPFRs) are emerging environmental pollutants that can be detected in water, dust, and biological organisms. Certain OPFRs can disrupt lipid metabolism in animal models and cell lines. However, the effects of OPFRs on human lipid metabolism remain unclear. We included 1,580 participants (≥20 years) from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between OPFR exposure and lipid metabolism biomarkers. After adjusting for confounding factors, results showed that one-unit increases in the log levels of diphenyl phosphate (DPhP) (regression coefficient = -5.755; S.E. = 2.289; p = 0.023) and log bis-(1-chloro-2-propyl) phosphate (BCPP) (regression coefficient = -4.637; S.E. = 2.019; p = 0.036) were negatively associated with the levels of total cholesterol (TC) in all participants. One-unit increases in the levels of DPhP (regression coefficient = -2.292; S.E. = 0.802; p = 0.012), log bis (1,3-dichloro-2-propyl) phosphate (BDCPP) (regression coefficient = -2.046; S.E. = 0.825; p = 0.026), and log bis-2-chloroethyl phosphate (BCEP) (regression coefficient = -2.604; S.E. = 0.704; p = 0.002) were negatively associated with the levels of high-density lipoprotein cholesterol (HDL-C). With increasing quartiles of urine BDCPP levels, the mean TC levels significantly decreased in all participants (p value for trend = 0.028), and quartile increases in the levels of DPhP (p value for trend = 0.01), BDCPP (p value for trend = 0.001), and BCEP (p value for trend<0.001) were negatively corelated with HDL-C, with approximately 5.9, 9.9, and 12.5% differences between the upper and lower quartiles. In conclusion, DPhP, BDCPP, and BCEP were negatively related to HDL-C concentration, whereas DPhP and BCPP levels were negatively associated with TC level. Thus, exposure to OPFRs may interfere with lipid metabolism.

Translocation of a fish spike from the pharynx to the thyroid gland: A case report.

BACKGROUND: A fish spike stuck in the throat is a common ear, nose, and throat (ENT) emergency. However, it is very rare for a fish spike to reach the thyroid tissue through the throat, which is very dangerous and can lead to pharyngeal fistula, cervical abscess, mediastinal abscess, and thyroid abscess. Proper and timely management can help reduce complications, especially in elderly patients. CASE SUMMARY: In the case presented here, the causative factor was dentures, but improper management aggravated the condition. In the case presented here, an elderly woman with a history of accidentally swallowing fish bones for 20 d had a sensation of foreign bodies in her throat. Eventually, computed tomography (CT) of the neck showed that the left side of the thyroid gland had a dense shadow in the form of a stripe. CONCLUSION: If a fishbone foreign body is not visible during endoscopic examination but the patient has significant symptoms, the surgeon should be aware that the fishbone may be lodged in the thyroid. To avoid a misdiagnosis, ultrasound, CT, and other tests can be used to clarify the diagnosis. T The first step in treating a fish bone in the thyroid gland is to determine the position of the foreign body and the extent of the infection, and to develop a personalized surgical plan for its removal. At the same time, scientific information should be made available to the general public so that people know that if a fish bone is accidentally lodged, they should not force it to be swallowed or be spit out by inducing vomiting, which are incorrect methods and may aggravate the condition or even cause it to migrate outside the cavity, leading to serious complications, as in this reported case.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. METHODS: The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. RESULTS: Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. CONCLUSION: Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.