Equitable infrastructure: Achieving resilient systems and restorative justice through policy and research innovation.

Recent major investments in infrastructure in the United States and globally present a crucial opportunity to embed equity within the heart of resilient infrastructure decision-making. Yet there is a notable absence of frameworks within the engineering and scientific fields for integrating equity into planning, design, and maintenance of infrastructure. Additionally, whole-of-government approaches to infrastructure, including the Justice40 Initiative, mimic elements of process management that support exploitative rather than exploratory innovation. These and other policies risk creating innovation traps that limit analytical and engineering advances necessary to prioritize equity in decision-making, identification and disruption of mechanisms that cause or contribute to inequities, and remediation of historic harms. Here, we propose a three-tiered framework toward equitable and resilient infrastructure through restorative justice, incremental policy innovation, and exploratory research innovation. This framework aims to ensure equitable access and benefits of infrastructure, minimize risk disparities, and embrace restorative justice to repair historical and systemic inequities. We outline incremental policy innovation and exploratory research action items to address and mitigate risk disparities, emphasizing the need for community-engaged research and the development of equity metrics. Among other action items, we recommend a certification system-referred to as Social, Environmental, and Economic Development (SEED)-to train infrastructure engineers and planners and ensure attentiveness to gaps that exist within and dynamically interact across each tier of the proposed framework. Through the framework and proposed actions, we advocate for a transformative vision for equitable infrastructure that emphasizes the interconnectedness of social, environmental, and technical dimensions in infrastructure planning, design, and maintenance.

Broiler Spaghetti Meat Abnormalities: Muscle Characteristics and Metabolomic Profiles.

Spaghetti meat (SM) is a newly identified muscle abnormality that significantly affects modern broiler chickens, consequently exerting a substantial economic impact on the poultry industry worldwide. However, investigations into the meat quality and the underlying causative factors of SM in broilers remain limited. Therefore, this study was undertaken to systematically evaluate meat quality and muscle fiber characteristics of SM-affected meat. To elucidate the disparities between SM-affected and normal (NO) muscles in broiler chickens reared under identical conditions, we selected 18 SM-affected breast tissues and 18 NO breast tissues from 200 broiler chickens raised according to commercial standards under the same conditions for our study. The results showed that compared with the NO group, the muscle surface of the SM group lost integrity, similar to strip and paste. The brightness and yellowness values were significantly higher than those of the NO group. On the contrary, the shear force and protein were significantly lower in the SM group. Microscopic examination revealed that the muscle fibers in the SM group were lysed, necrotic, and separated from each other, with a large number of neutrophils diffusely distributed on the sarcolemma and endometrium. Thirty-five significantly different metabolites were observed in the breast muscles between both groups. Among them, the top differential metabolites-14,15-DiHETrE, isotretinoin, L-malic acid, and acetylcysteine-were mainly enriched in lipid metabolism and inflammatory pathways, including linoleic acid, arachidonic acid, phenylalanine, and histidine metabolism. Overall, these findings not only offer new insights into the meat quality and fiber traits of SM but also contribute to the understanding of potential mechanisms and nutritional regulators for SM myopathy.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Semi-Supervised 3D Shape Segmentation via Self Refining.

3D shape segmentation is a fundamental and crucial task in the field of image processing and 3D shape analysis. To segment 3D shapes using data-driven methods, a fully labeled dataset is usually required. However, obtaining such a dataset can be a daunting task, as manual face-level labeling is both time-consuming and labor-intensive. In this paper, we present a semi-supervised framework for 3D shape segmentation that uses a small, fully labeled set of 3D shapes, as well as a weakly labeled set of 3D shapes with sparse scribble labels. Our framework first employs an auxiliary network to generate initial fully labeled segmentation labels for the sparsely labeled dataset, which helps in training the primary network. During training, the self-refine module uses increasingly accurate predictions of the primary network to improve the labels generated by the auxiliary network. Our proposed method achieves better segmentation performance than previous semi-supervised methods, as demonstrated by extensive benchmark tests, while also performing comparably to supervised methods.

G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation.

Adipose tissue is the second most important site of estrogen production, where androgens are converted into estrogen by aromatase. While gastric cancer patients often develop adipocyte-rich peritoneal metastasis, the underlying mechanism remains unclear. In this study, we identified the G-protein-coupled estrogen receptor (GPER1) as a promoter of gastric cancer peritoneal metastasis. Functional in vitro studies revealed that ß-Estradiol (E2) or the GPER1 agonist G1 inhibited anoikis in gastric cancer cells. Additionally, genetic overexpression or knockout of GPER1 significantly inhibited or enhanced gastric cancer cell anoikis in vitro and peritoneal metastasis in vivo, respectively. Mechanically, GPER1 knockout disrupted the NADPH pool and increased reactive oxygen species (ROS) generation. Conversely, overexpression of GPER1 had the opposite effects. GPER1 suppressed nicotinamide adenine dinucleotide kinase 1(NADK1) ubiquitination and promoted its phosphorylation, which were responsible for the elevated expression of NADK1 at protein levels and activity, respectively. Moreover, genetic inhibition of NADK1 disrupted NADPH and redox homeostasis, leading to high levels of ROS and significant anoikis, which inhibited lung and peritoneal metastasis in cell-based xenograft models. In summary, our study suggests that inhibiting GPER1-mediated NADK1 activity and its ubiquitination may be a promising therapeutic strategy for peritoneal metastasis of gastric cancer.

Association between Dietary Intake of Live Microbes and Chronic Constipation in Adults.

BACKGROUND: Chronic constipation (CC) is a common gut health problem, and the role of live dietary microbes in CC is unclear. OBJECTIVE: This study aimed to investigate the relationship between dietary live microbes consumption and CC. METHODS: Using the National Health and Nutrition Examination Survey data (2005-2010), 11,170 adults who completed the 24-h face-to-face dietary recall and bowel health questionnaire were identified. CC was defined by the Bristol Stool Form Scale. Dietary live microbes intake was classified as low, medium, and high. Additionally, combined medium and high categories (MedHi) were analyzed. Multivariate regression models were constructed to assess the association between dietary intake of live microbes and CC. RESULTS: In the weighted sample, the age-adjusted CC prevalence was 7.06% (95% confidence interval [CI]: 6.45, 7.67). In multivariate regression models, after controlling for potential confounders race/ethnicity, sex, body mass index, education, poverty, depression, caffeine intake, and alcohol intake, a significant inverse association between dietary live microbes consumption and CC was observed (odds ratio [OR]: 0.77, 95% CI: 0.61, 0.97, P-trend = 0.061). CONCLUSIONS: Our findings suggest that a high dietary live microbes consumption may be associated with lower odds of CC. However, further prospective studies are essential to confirm its effectiveness in reducing CC occurrence.

Therapeutic effect of yinchenhao decoction on cholelithiasis via mucin in the gallbladder and intestine.

Cholelithiasis is a common and frequently occurring disease worldwide that belongs to the category of jaundice in traditional Chinese medicine. Yinchenhao decoction (YD) consists of Artemisia capillaris Thunb., Gardenia jasminoides J.Ellis, and Rheum palmatum L., and is traditionally used to treat jaundice, which has a significant therapeutic effect on cholelithiasis. Our study aimed to investigate the pathological mechanism of cholelithiasis and the therapeutic mechanism of YD via mucin in the gallbladder and intestine. YD was prepared and analyzed using HPLC. The supersaturation stability experiment was designed by the solvent-shift method. The cell transport experiment was conducted by coculture monolayers. The animal experiment was performed using a cholelithiasis model with a high-cholesterol diet. The related indicators were detected by automatic biochemical analyzer, PCR, western blot, or ELISA. Statistics were analyzed using χ2-tests and t-tests. As the results, in cholelithiasis, MUC5AC highly expressed in the gallbladder shortened cholesterol supersaturation and promoted cholesterol crystallization via the inflammatory cytokine signaling pathway; MUC2 highly expressed in the small intestine prolonged cholesterol supersaturation and promoted cholesterol absorption via the inflammatory cytokine signaling pathway. YD inhibited mucin expression in the gallbladder and intestine in a concentration-dependent manner for cholelithiasis treatment by inhibiting the inflammatory cytokine signaling pathway, which was attributed to the active components, including chlorogenic acid, geniposide, and rhein.

Research trends and frontiers in lupus nephritis: a bibliometric analysis from 2012 to 2022.

OBJECTIVES: Lupus nephritis is a prevalent renal manifestation of systemic lupus erythematosus (SLE) and represents a significant cause of morbidity and mortality associated with the disease. This study endeavors to undertake a meticulous bibliometric analysis of LN publications to comprehend the research hotspots and future directions. METHODS: The literature on LN was acquired from the Web of Science Core Collection (WoSCC). Co-occurrence and cooperative relationship analysis of authors, institutions, countries, journals, references and keywords in the publication was performed through CiteSpace, VOSviewer and a bibliometric online analysis platform. The knowledge graphs were created, and clustering and emergence analyses were performed. RESULTS: According to the search strategy, a total of 2077 publications related to lupus nephritis (LN) have been identified, with China being the largest contributor globally. The Ohio State University emerged as the most prolific institution. Lupus is the most cited and published journal. Jan J Weening and Brad Rovin were the most prolific and cocited authors. The current research focus revolved around the "nirp3 inflammasome," "biomarker," and "voclosporin". "international society," "thrombotic microangiopathy (TMA)," and "pathway" were identified to be future research hotpots by keyword burst analysis. CONCLUSIONS: This bibliometric analysis summarizes for the first time the progress of LN research (2012-2022), and qualitatively and quantitatively evaluates the bibliometric information of LN research. There has been a steady increase in the scientific literature on LN over the past 11 years, with an average growth rate of 7.27%. In this field, researchers are primarily based in China and the United States. The pathogenic mechanisms, management strategies and prognostic outcomes of LN are acknowledged as prospective research hotspots. Bibliometrically, the research status and trends of LN publications may greatly assist and be a significant reference for future research in the area.

Genetic Diversity Analysis and Breeding of Geese Based on the Mitochondrial ND6 Gene.

To explore the differences in body-weight traits of five goose breeds and analyze their genetic diversity and historical dynamics, we collected body-weight data statistics and used Sanger sequencing to determine the mitochondrial DNA of 100 samples of five typical goose breeds in China and abroad. The results indicated that Lion-Head, Hortobagy, and Yangzhou geese have great breeding potential for body weight. Thirteen polymorphic sites were detected in the corrected 505 bp sequence of the mitochondrial DNA (mtDNA) ND6 gene, accounting for approximately 2.57% of the total number of sites. The guanine-cytosine (GC) content (51.7%) of the whole sequence was higher than the adenine-thymine (AT) content (48.3%), showing a certain GC base preference. There were 11 haplotypes among the five breeds, including one shared haplotype. We analyzed the differences in the distribution of base mismatches among the five breeds and conducted Tajima's D and Fu's Fs neutral tests on the historical dynamics of the populations. The distribution of the mismatch difference presented an unsmooth single peak and the Tajima's D value of the neutral test was negative (D < 0) and reached a significant level, which proves that the population of the three species had expanded; the Lion-Head goose population tends to be stable. The genetic diversity of Lion-Head, Zhedong White, Yangzhou, and Taihu geese was equal to the average diversity of Chinese goose breeds. The Hortobagy goose is a foreign breed with differences in mating line breeding and hybrid advantage utilization.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

Probing the interaction between metastatic breast cancer cells and osteoblasts in a thread-based breast-bone co-culture device.

Breast cancer metastasis to bone is a leading killer in breast cancer patients. A type I collagen-modified thread (Col-I@thread) was prepared for 3-dimensional cell culture and breast cancer bone metastasis co-culture device assembly. First, the coating of Col-I on nylon threads for promoting cell adhesion and growth was studied. Through SEM, XPS, and protein concentration measurements, it was found that the lyophilization method remarkably preserved the Col-I activity and the internal structure of the thread, thereby promoting cell attachment and proliferation. RNA-sequencing (RNA-Seq) and quantitative PCR analysis showed that osteoblast cells (MC3T3-E1) grown on Col-I@thread had elevated RUNX2, ALP, OPN, and Col-I gene expression to promote osteoblast differentiation. Single-cell analysis found that osteoblast MC3T3-E1 cells growing on Col-I@thread had higher Ca2+ secretion activity and mineralized nodules, suggesting robust cell activity and bone matrix formation than cells growing on 2D culture plates. Col-I@threads were knotted in an interdigital cross-finger frame to assemble the breast cancer-bone co-culture model. Confocal microscopy and flow cytometry tests quantified the invasive breast cancer cells. Moreover, the thread-based co-culture devices allowed us to isolate the invasive and non-invasive breast cancer cells to compare their molecular characteristics. qPCR results showed that expression of CX43, CXCR5, and CSPG4 genes was significantly increased in breast cancer cells with bone metastasis. Meanwhile, the expression of RUNX2 and OPG genes in osteoblasts was inhibited. The co-culture model based on the Col-I@thread mimics the bone tissue microenvironment to reveal the cross-talk between cancer cells and bone tissue. Moreover, the thread-based co-culture device is easy to fabricate and operate, providing a platform for exploring the cellular and molecular mechanisms of breast cancer bone metastasis, and holds potential for high-throughput screening of anti-breast cancer bone metastasis drugs.

Difficult-to-treat rheumatoid arthritis treated with Abatacept combined with Baricitinib: A case report.

BACKGROUND: Sporadic cases of rheumatoid arthritis (RA) due to unsatisfactory responses to Abatacept (ABT) have been reported; however, the rescue therapy has not been finalized. Here, we present a case with difficult-to-treat RA (D2T RA) that was resistant to either a single ABT or a Janus kinase (JAK) inhibitor (Tofacitinib), but improved with a combination of ABT and JAK inhibitor (Baricitinib, BAT). CASE SUMMARY: A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab, Etanercept, Adalimumab, and ABT. According to the European League Against Rheumatism definition, the patient was diagnosed with D2T RA. It was then improved with a combination of ABT and a JAK inhibitor BAT. CONCLUSION: ABT combined with BAT may be an acceptable strategy for treating D2T RA.

Femtotesla Atomic Magnetometer Employing Diffusion Optical Pumping to Search for Exotic Spin-Dependent Interactions.

Searching for beyond-the-standard-model interactions has been of interest in quantum sensing. Here, we demonstrate a method, both theoretically and experimentally, to search for the spin- and velocity-dependent interaction with an atomic magnetometer at the centimeter scale. By probing the diffused optically polarized atoms, undesirable effects coming along with the optical pumping, such as light shifts and power-broadening effects, are suppressed, which enables a 1.4 fT_{rms}/Hz^{1/2} noise floor and the reduced systematic errors of the atomic magnetometer. Our method sets the most stringent laboratory experiment constraints on the coupling strength between electrons and nucleons for the force range λ>0.7 mm at 1σ confidence. The limit is more than 3 orders of magnitude tighter than the previous constraints for the force range between 1 mm∼10 mm, and one order of magnitude tighter for the force range above 10 mm.

Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice.

Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.

A movable unshielded magnetocardiography system.

Magnetocardiography (MCG), which uses high-sensitivity magnetometers to record magnetic field signals generated by electrical activity in the heart, is a noninvasive method for evaluating heart diseases such as arrhythmia and ischemia. The MCG measurements usually require the participant keeping still in a magnetically shielded room due to the immovable sensor and noisy external environments. These requirements limit MCG applications, such as exercise MCG tests and long-term MCG observations, which are useful for early detections of heart diseases. Here, we introduce a movable MCG system that can clearly record MCG signals of freely behaving participants in an unshielded environment. On the basis of optically pumped magnetometers with a sensitivity of 140 fT/Hz1/2, we successfully demonstrated the resting MCG and the exercise MCG tests. Our method is promising to realize a practical movable multichannel unshielded MCG system that nearly sets no limits to participants and brings another kind of insight into the medical diagnosis of heart disease.

Automatic classification of arrhythmias using multi-branch convolutional neural networks based on channel-based attention and bidirectional LSTM.

Cardiac arrhythmia is an abnormal rhythm of the heartbeat and can be life-threatening Electrocardiogram (ECG) is a technology that uses an electrocardiograph machine to record a graph of the changes in electrical activity produced by the heart at each cardiac cycle. ECG can generally be used to check whether the examinee has arrhythmia, ion channel disease, cardiomyopathy, electrolyte disorder and other diseases. To reduce the workload of doctors and improve the accuracy of ECG signal recognition, a novel and lightweight automatic ECG classification method based on Convolutional Neural Network (CNN) is proposed. The multi-branch network with different receptive fields is used to extract the multi-spatial deep features of heartbeats. The Channel Attention Module (CAM) and Bidirectional Long Short-Term Memory neural network (BLSTM) module are used to filter redundant ECG features. CAM and BLSTM are beneficial for distinguishing different categories of heartbeats. In the experiments, a four-fold cross-validation technique is used to improve the generalization capability of the network, and it shows good performance on the testing set. This method divides heartbeats into five categories according to the American Advancement of Medical Instrumentation (AAMI) criteria, which is validated in the MIT-BIH arrhythmia database. The sensitivity of this method to Ventricular Ectopic Beat (VEB) is 98.5% and the F1 score is 98.2%. The precision of the Supraventricular Ectopic Beat (SVEB) is 91.1%, and the corresponding F1 score is 90.8%. The proposed method has high classification performance and a lightweight feature. In a word, it has broad application prospects in clinical medicine and health testing.

Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis.

Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged < 18 years) who underwent dual genomic sequencing were enrolled in this retrospective multicentre study. We evaluated the mitochondrial disease criteria (MDC) and molecular diagnostic yield of dual genomic sequencing. Causative variants were identified in 177 out of 503 (35.2%) patients using dual genomic sequencing. Forty-six patients (9.1%) had mitochondria-related variants, including 25 patients with nuclear DNA (nDNA) variants, 15 with mitochondrial DNA (mtDNA) variants, and six with dual genomic variants (MT-ND6 and POLG; MT-ND5 and RARS2; MT-TL1 and NARS2; MT-CO2 and NDUFS1; MT-CYB and SMARCA2; and CHRNA4 and MT-CO3). Based on the MDC, 15.2% of the patients with mitochondria-related variants were classified as "unlikely to have mitochondrial disorder". Moreover, 4.5% of the patients with non-mitochondria-related variants and 1.43% with negative genetic tests, were classified as "probably having mitochondrial disorder". Dual genomic sequencing in suspected MDs provided a more comprehensive and accurate diagnosis for pediatric patients, especially for patients with dual genomic variants.

Myocardin-related transcription factor A, regulated by serum response factor, contributes to diabetic cardiomyopathy in mice.

AIMS: Diabetic cardiomyopathy is a significant contributor to the global pandemic of heart failure. In the present study we investigated the involvement of myocardin-related transcription factor A (MRTF-A), a transcriptional regulator, in this process. MATERIALS AND METHODS: Diabetic cardiomyopathy was induced in mice by feeding with a high-fat diet (HFD) or streptozotocin (STZ) injection. KEY FINDINGS: We report that MRTF-A was up-regulated in the hearts of mice with diabetic cardiomyopathy. MRTF-A expression was also up-regulated by treatment with palmitate in cultured cardiomyocytes in vitro. Mechanistically, serum response factor (SRF) bound to the MRTF-A gene promoter and activated MRTF-A transcription in response to pro-diabetic stimuli. Knockdown of SRF abrogated MRTF-A induction in cardiomyocytes treated with palmitate. When cardiomyocytes conditional MRTF-A knockout mice (MRTF-A CKO) and wild type (WT) mice were placed on an HFD to induce diabetic cardiomyopathy, it was found that the CKO mice and the WT mice displayed comparable metabolic parameters including body weight, blood insulin concentration, blood cholesterol concentration, and glucose tolerance. However, both systolic and diastolic cardiac function were exacerbated by MRTF-A deletion in the heart. SIGNIFICANCE: These data suggest that MRTF-A up-regulation might serve as an important compensatory mechanism to safeguard the deterioration of cardiac function during diabetic cardiomyopathy.

Bismuth(III)-Catalyzed 1,8-Addition/Cyclization/Rearrangement of Propargylic para-Quinone Methides with 2-Vinylphenol: Synthesis of Indeno[2,1-c]chromenes.

The unique reactivity of in situ generated propargylic para-quinone methides as a new type of five-carbon synthon has been discovered by a novel bismuth(III)-catalyzed tandem annulation reaction. This 1,8-addition/cyclization/rearrangement cyclization cascade reaction is characterized by unusual structural reconstruction of 2-vinylphenol, involving cleavage of the C1'═C2' bond and formation of four new bonds. This method provides a convenient and mild approach to generate synthetically important functionalized indeno[2,1-c]chromenes. The mechanism of the reaction is proposed from several control experiments.