Total Synthesis and Stereochemical Assignment of Roselipin 1A.

Roselipin 1A, a bioactive natural glycolipid isolated from marine fungal metabolites, presents an unresolved configuration of its nine stereogenic centers within the polyketide chain. Herein, we elucidate the comprehensive stereostructure of roselipin 1A through an integrative approach combining predictive rule-guided analysis with synthetic chemistry. The efficient total synthesis facilitated the unequivocal confirmation of the hypothesized stereochemistry for roselipin 1A, thereby establishing its precise molecular configuration.

Synergy of Prediction Rule and Total Synthesis in Solving the Stereochemical Puzzle of Valactamides.

Natural products with diverse functional groups and stereogenic centers have inspired therapeutics and underpin the modern drug discovery process. Their three-dimensional molecular structures need to be unambiguously determined in order to be realized as clinical candidates or to achieve further activity-guided structural optimization. Although recent advances in spectroscopic methods have made it possible for researchers to determine the structures of microgram samples of complex natural products, there is no universally accepted method for determining the relative and absolute configuration of a naturally occurring compound.

Internalizing Symptoms and Their Impact on Patient-Reported Health-Related Quality of Life and Fatigue among Patients with Craniopharyngioma During Proton Radiation Therapy.

Objective: The aim of this study was to describe fatigue, health-related quality of life (HRQOL) and brain tumor-associated symptoms after surgical resection and during proton radiotherapy, using latent class analysis (LCA), and to determine if there is class membership change among pediatric patients with craniopharyngioma.

Methods: For all patients ( = 92), demographic and disease-related/clinical variables were attained, and patient reported outcomes were collected prior to proton therapy, at week three, and at the completion of proton therapy. The mean scores for fatigue, HRQOL, and brain tumor symptoms were compared over time and profiles were identified.

Total Synthesis of Rhizopodin Enabled by a Late-Stage Oxazole Ring Formation Strategy.

Actin stabilizers that are capable of interfering with actin cytoskeleton dynamics play an important role in chemical biology. Rhizopodin, a novel actin stabilizer, affects the actin cytoskeleton at nanomolar concentrations and exhibits potent antiproliferative activities against a range of tumor cell lines with IC values in the low nanomolar range. Herein, we report the total synthesis of rhizopodin based on a late-stage oxazole ring formation strategy, whose success demonstrates the feasibility of late-stage oxazole ring formation in the synthesis of complex oxazole containing natural products.

Total Syntheses and Stereochemical Assignment of Acremolides A and B.

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B.

Maternal empowerment, feeding knowledge, and infant nutrition: Evidence from rural China.

Background: Maternal empowerment - the capacity to make decisions within households - is linked to better child feeding and nutritional outcomes, but few studies have considered the mediating role of caregiver knowledge. Further, existing literature centres primarily on the husband-wife dyad while overlooking grandmothers as important childcare decision-makers.

Methods: We collected primary data through household surveys in 2019 and 2021 from 1190 households with infants zero to six months living in rural western China.

Performance and symptom validity indicators among children undergoing cognitive surveillance following treatment for craniopharyngioma.

Background: Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to neuropsychological evaluations, helping ensure findings reflect true abilities or concerns. It is unclear how PVTs and SVTs perform in children who received radiotherapy for brain tumors. Accordingly, we investigated the rate of noncredible performance on validity indicators as well as associations with fatigue and lower intellectual functioning.

Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma.

Neuroblastoma with MYCN amplification (MNA) is a high-risk disease that has a poor survival rate. Neuroblastoma displays cellular heterogeneity, including more differentiated (adrenergic) and more primitive (mesenchymal) cellular states. Here, we demonstrate that MYCN oncoprotein promotes a cellular state switch in mesenchymal cells to an adrenergic state, accompanied by induction of histone lysine demethylase 4 family members (KDM4A-C) that act in concert to control the expression of MYCN and adrenergic core regulatory circulatory (CRC) transcription factors.

The Relationship Between Health Insurance Status and Diabetic Retinopathy Progression.

Objective: To determine if baseline diabetic retinopathy (DR) severity mediates the relationship between health insurance status and DR progression.

Design: Retrospective cohort study.

Subjects: Seven hundred sixteen patients aged ≥ 18 years with a diagnosis of type 1 or 2 diabetes mellitus, and a diagnosis of nonproliferative DR (NPDR) were identified from the electronic health record of a tertiary academic center between June 2012 and February 2022.

Total Synthesis of Incarnatapeptins A and B.

The first total synthesis of incarnatapeptins A and B, two novel marine natural products, was accomplished from readily available (S)-1-benzyloxycarbonylhexahydropyridazine-3-carboxylic acid. This route, whose longest linear sequence was 12 steps, provided the incarnatapeptins A and B in yields of 26.5 % and 19.

Total Synthesis of Nicrophorusamide A and Structural Disproof of the Proposed Noursamycin A.

Total synthesis of the proposed noursamycin A has been accomplished, which disproves the original structural assignments. The synthetic strategy described herein has also been employed in the first total synthesis of nicrophorusamide A, a cyclopeptide that is structurally related to noursamycin A.

Associations of in-hospital postpartum feeding experiences with exclusive breastfeeding practices among infants in rural Sichuan, China.

Background: In rural China, exclusive breastfeeding (EBF) prevalence is low and hospitals often fail to attain baby-friendly feeding objectives, such as ≥ 75% of newborns exclusively breastfed from birth to discharge. Empirical evidence for the impact of increased hospital compliance with recommended feeding guidelines on continued EBF in rural China is lacking. We sought to measure and model the association of newborns' in-hospital feeding experiences with EBF practice in infancy to inform policies for EBF promotion.

Developing and Validating Models to Predict Progression to Proliferative Diabetic Retinopathy.

Purpose: To develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance.

Design: Retrospective cohort study.

Participants: Electronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR).

Effect of the mHealth-supported Healthy Future programme delivered by community health workers on maternal and child health in rural China: study protocol for a cluster randomised controlled trial.

Introduction: Millions of young rural children in China still suffer from poor health and malnutrition, partly due to a lack of knowledge about optimal perinatal and child care among rural mothers and caregivers. Meanwhile, there is an urgent need to improve maternal mental health in rural communities. Comprehensive home visiting programmes delivered by community health workers (CHWs) can bridge the caregiver knowledge gap and improve child health and maternal well-being in low-resource settings, but the effectiveness of this approach is unknown in rural China.

Development of Clinical Risk Scores for Detection of COVID-19 in Suspected Patients During a Local Outbreak in China: A Retrospective Cohort Study.

To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests.

Postnatal mental health, breastfeeding beliefs, and breastfeeding practices in rural China.

Background: The importance of breastfeeding in low- and middle- income countries is well recognized, yet the importance of postnatal mental health on breastfeeding practices and beliefs in these settings has been understudied. This study investigates the associations between maternal mental health problems, breastfeeding beliefs and breastfeeding practices in rural China.

Methods: Cross-sectional data were collected in November and December 2019 from 742 mothers of infants under 6 months old in rural Sichuan Province, China.

Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma.

Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1 RMS.

Determinants of breastfeeding self-efficacy among postpartum women in rural China: A cross-sectional study.

Background: Breastfeeding self-efficacy is known to positively influence breastfeeding behaviors. While previous research has studied the determinants of breastfeeding self-efficacy in general, these determinants are unstudied among postpartum women in rural China. This study aims to describe the breastfeeding self-efficacy of postpartum women in rural China and identify determinants of breastfeeding self-efficacy using the Dennis breastfeeding self-efficacy framework.

Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy.

Purpose: Vasculopathy (VAS) is a significant complication associated with radiation therapy in patients treated for brain tumors. We studied the type, location, severity, timing, and resolution of VAS in children with craniopharyngioma treated with proton radiation therapy (PRT) and evaluated predictors of stenosis (STN) using a novel patient and imaging-based modeling approach.

Methods And Materials: Children with craniopharyngioma (n = 94) were treated with 54 Gy relative biological effectiveness PRT in a clinical trial, NCT01419067.

Perinatal Mental Health Problems in Rural China: The Role of Social Factors.

Perinatal mental health is important for the well-being of the mother and child, so the relatively high prevalence of perinatal mental health problems in developing settings poses a pressing concern. However, most studies in these settings focus on the demographic factors associated with mental health problems, with very few examing social factors. Hence, this study examines the prevalence of the depressive, anxiety and stress symptoms among pregnant women and new mothers in rural China, and the associations between these mental health problems and social factors, including decision-making power, family conflicts, and social support.

Postnatal Mental Health, Hand Washing Practices, and Infant Illness in Rural China.

Maternal mental health problems play an important role in infant well-being. Although western countries have extensively studied the associations between maternal mental disorders, hygiene practices and infant health, little is known in developing settings. This study investigates the correlations between postnatal mental health problems, hand washing practices and infant illness in rural western China.

Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning.

Purpose: To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03.

Patients And Methods: Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.

Biochemistry-Guided Prediction of the Absolute Configuration of Fungal Reduced Polyketides.

Highly reducing polyketide synthases (HR-PKSs) produce structurally diverse polyketides (PKs). The PK diversity is constructed by a variety of factors, including the β-keto processing, chain length, methylation pattern, and relative and absolute configurations of the substituents. We examined the stereochemical course of the PK processing for the synthesis of polyhydroxy PKs such as phialotides, phomenoic acid, and ACR-toxin.

Total Synthesis of Pagoamide A.

The first total synthesis of the thiazole-containing cyclic depsipeptide pagoamide A, is detailed. The longest linear sequence of the liquid-phase synthesis comprises 9 long linear steps from simple known starting materials, which led to the unambiguous structural confirmation of pagoamide A.