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BackgroundBrain network dysfunction has been characterized by resting-state electroencephalography (EEG) and magnetic resonance imaging (MRI) in the prodromal stage. This study aimed to identify multi-modal electrophysiological and neuroimaging biomarkers for differential diagnosis in synucleinopathies and phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD).MethodsWe enrolled 35 patients with multiple system atrophy (MSA), 32 with Parkinson's disease (PD), 30 with iRBD and 30 matched healthy controls (HC). Power spectral density (PSD) was calculated in different frequency bands. EEG functional connectivity (FC) was calculated using the weighted Phase Lag Index (wPLI) after source localization. Significant network disruptions were further confirmed by MRI FC analysis.ResultsQuantitative EEG analysis demonstrated that delta and theta power spectral density significantly differed among MSA, PD and HC. The increased PSD was correlated with cognitive decline and olfactory dysfunction in PD. Band-specific FC profiles were observed in theta, alpha, and gamma bands. The hypoconnected alpha network significantly correlated with motor dysfunction, while the gamma FC distinguished PD from MSA. By integrating EEG and MRI network analyses, we found that FC between the olfactory cortex and dorsolateral prefrontal cortex was significantly different between MSA and PD. A multimodal discriminative model for MSA and PD, integrating spectral and FC attributes of EEG and MRI, yielded an area under the receiver operating characteristic curve of 0.900. Simultaneously, we found the FC abnormalities were more prominent than spectral features in iRBD indicating prodromal dysfunction. The decreased FC between the angular gyrus and striatum was identified in α-synucleinopathies. This hypoconnectivity was associated with dopaminergic degeneration in iRBD examined by dopamine transporter imaging.DiscussionOur study demonstrated EEG spectral and functional profiles in prodromal and clinical-defined synucleinopathies. Multimodal EEG and MRI provided a novel approach to discriminate MSA and PD, and monitor neurodegenerative progression in the preclinical phase.

BackgroundAsthenozoospermia, a type of male infertility, is primarily caused by dysfunctional sperm mitochondria. Despite previous bioinformatics analysis identifying potential key lncRNAs, miRNAs, hub genes, and pathways associated with asthenospermia, there is still a need to explore additional molecular mechanisms and potential biomarkers for this condition.MethodsWe integrated data from Gene Expression Omnibus (GEO) (GSE22331, GSE34514, and GSE160749) and performed bioinformatics analysis to identify differentially expressed genes (DEGs) between normozoospermia and asthenozoospermia. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to gain insights into biological processes and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with asthenozoospermia. Expression levels of key genes were assessed using datasets and experimental data. Gene Set Enrichment Analysis (GSEA) and correlation analysis identified pathways associated with the hub gene and explore the relationship between the ZNF764 and COQ9 and mitochondrial autophagy-related genes. Competitive endogenous RNA (ceRNA) networks were constructed, and in vitro experiments using exosome samples were conducted to validate this finding.ResultsCOQ9 was identified as a marker gene in asthenozoospermia, involved in autophagy, ATP-dependent chromatin remodeling, endocytosis, and cell cycle, etc. The ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) was constructed, and PCR demonstrated that LINC00893 and COQ9 were downregulated in asthenozoospermia, while miR-125a-5p and m6A methylation level of LINC00893 were upregulated in asthenozoospermia compared to normozoospermic individuals.ConclusionThe ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) likely plays a crucial role in the mechanism of asthenozoospermia. However, further functional experiments are needed to fully understand its significance.

BackgroundEpidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS).ObjectiveWe aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal associations between both disorders and peripheral iron status.MethodsWe performed two-sample Mendelian randomization (MR) analyses using summary statistics from genome-wide meta-analyses of ADHD, RLS, and peripheral iron status (serum iron, ferritin, transferrin saturation, and total iron binding capacity). Additionally, we employed linkage disequilibrium score regression (LDSC) to assess genetic correlations between ADHD and RLS using genetic data.ResultsOur MR results supports a causal effect from ADHD (as exposure) to RLS (as outcome) (inverse variance weighted OR = 1.20, 95% CI: 1.08-1.34, p = 0.001). Conversely, we found no a causal association from RLS to ADHD (inverse variance weighted OR = 1.04, 95% CI: 0.99-1.09, p = 0.11). LDSC analysis did not detect a significant genetic correlation between RLS and ADHD (Rg = 0.3, SE = 0.16, p = 0.068). Furthermore, no evidence supported a causal relationship between peripheral iron deficiency and the RLS or ADHD onset. However, RLS may have been associated with a genetic predisposition to reduced serum ferritin levels (OR = 1.20, 95% CI: 1.00-1.04, p = 0.047).ConclusionThis study suggests that ADHD is an independent risk factor for RLS, while RLS may confer a genetic predisposition to reduced serum ferritin levels.LimitationsThe GWAS summary data utilized originated from populations of European ancestry, limiting the generalizability of conclusions to other populations.Clinical implicationsThe potential co-occurrence of RLS in individuals with ADHD should be considered during diagnosis and treatment. Moreover, iron supplementation may be beneficial for alleviating RLS symptoms.

Summary: Neutrophils are important innate immune cells with plasticity, heterogenicity, and functional ambivalency. While bone marrow is often regarded as the primary source of neutrophil production, the roles of extramedullary production in regulating neutrophil plasticity and heterogenicity in autoimmune diseases remain poorly understood. Here, we report that the lack of wingless-type MMTV integration site family member 5 (WNT5) unleashes anti-inflammatory protection against colitis in mice, accompanied by reduced colonic CD8+ T cell activation and enhanced splenic extramedullary myelopoiesis. In addition, colitis upregulates WNT5 expression in splenic stromal cells. The ablation of WNT5 leads to increased splenic production of hematopoietic niche factors, as well as elevated numbers of splenic neutrophils with heightened CD8+ T cell suppressive capability, in part due to elevated CD101 expression and attenuated pro-inflammatory activities. Thus, our study reveals a mechanism by which neutrophil plasticity and heterogenicity are regulated in colitis through WNT5 and highlights the role of splenic neutrophil production in shaping inflammatory outcomes.

Summary: The dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8+ T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8+ T cell metabolic and functional fitness. De novo NAD+ synthesis is involved in CD8+ T cell metabolism and antitumor function. KP-derived NAD+ promotes PTEN deacetylation, thereby facilitating PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, impaired cell-autonomous NAD+ synthesis limits CD8+ T cell responses in human colorectal cancer samples. Our results reveal that KP-derived NAD+ regulates the CD8+ T cell metabolic and functional state by restricting PTEN activity and suggest that modulation of de novo NAD+ synthesis could restore CD8+ T cell metabolic fitness and antitumor function.

Objective: This study was determined to investigate the impact of intranasal dexmedetomidine (DEX) on postoperative sleep quality in older patients (age over 65) with chronic insomnia during their hospitalization after surgery.Design: A randomized double-blind controlled trial was conducted to compare the effects of intranasal dexmedetomidine spray with a placebo group.Setting and Participants: The study was carried out at Xiangya Hospital, Central South University. 110 participants with chronic insomnia were analyzed.Methods: This trial enrolled older patients who underwent total hip/knee arthroplasty and randomized them to receive intranasal dexmedetomidine (2.0 μg/kg) or saline daily at around 9 p.m. after surgery until discharge. The primary outcomes were subjective sleep quality assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ). The secondary outcomes included the objective sleep quality measured with the Acti-graph, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI). The other outcomes included the incidence of delirium, levels of inflammatory factors, visual analog scale (VAS) pain scores, postoperative opioid consumption, and treatment-related adverse events.Results: 174 patients were screened for eligibility, and 110 were recruited and analyzed. The DEX group had significantly higher scores on both the LSEQ-Getting to sleep and LSEQ-Quality of Sleep at each time point compared to the placebo (p < 0.0001), The least squares (LS) mean difference in LSEQ-GTS score at T0 between placebo group and DEX group was 2 (95% CI, −1–6), p = 0.4071 and at T5 was −14 (95% CI, −17 to −10), p < 0.0001; The LS mean difference in the LSEQ-QOS score at T0 was −1 (95% CI, −4 to 1), p = 0.4821 and at T5 was −16 (95% CI, −21 to −10), p < 0.0001. The DEX group exhibited significant improvement in Total Sleep Time (TST), Sleep Onset Latency (SOL), and Sleep Efficiency (SE), at each time point after treatment compared to the placebo group (p < 0.0001). The PSQI and ISI scores in the DEX group were reduced after treatment (p < 0.001). No significant adverse events were reported with the use of dexmedetomidine.Conclusion and Implications: This study demonstrates that intranasal administration of dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia who undergo surgery, without increasing the incidence of adverse effects.Clinical Trial Registration:http://www.chictr.org.cn/, identifier ChiCTR2200057133

Spatiotemporal separation of cellular components is vital to ensure biochemical processes. Membrane-bound organelles such as mitochondria and nuclei play a major role in isolating intracellular components, while membraneless organelles (MLOs) are accumulatively uncovered via liquid-liquid phase separation (LLPS) to mediate cellular spatiotemporal organization. MLOs orchestrate various key cellular processes, including protein localization, supramolecular assembly, gene expression, and signal transduction. During viral infection, LLPS not only participates in viral replication but also contributes to host antiviral immune responses. Therefore, a more comprehensive understanding of the roles of LLPS in virus infection may open up new avenues for treating viral infectious diseases. In this review, we focus on the antiviral defense mechanisms of LLPS in innate immunity and discuss the involvement of LLPS during viral replication and immune evasion escape, as well as the strategy of targeting LLPS to treat viral infectious diseases.

Abstract In colorectal cancer (CRC), the development of reagents that increase sensitivity to chemotherapeutic agents could prevent drug resistance and improve patient survival. Scm-like with four malignant brain tumor domains 1 (SFMBT1) is up-regulated in CRC tumor tissues and cells and may be associated with drug resistance. We detected the expression of SFMBT1 in CRC tissue microarrays by immunohistochemistry. The role of SFMBT1 in the migration, proliferation and invasion of CRC or resistance to 5-fluorouracil (5-FU) was determined using scratch assay, colony formation and Transwell assay. Fluorescence co-localization and immunoprecipitation were used to analyze the correlation between SFMBT1 and high mobility group domain-containing protein 20 A (HMG20A). Xenograft experiments were conducted to investigate the role of SFMBT1 and HMG20A in tumor growth and metastasis in vivo. We found that SFMBT1 is up-regulated in CRC and its expression is further amplified in 5-FU resistance. SFMBT1 drives 5-FU resistance and CRC proliferation, migration and invasion. Correlation analysis shows that SFMBT1 and HMG20A are positively correlated. Mechanistically, fluorescence co-localization and immunoprecipitation assay indicate an interaction between SFMBT1 and HMG20A. Depletion of SFMBT1 down-regulates HMG20A downstream. These results were verified by murine xenograft and lung metastasis models. Our results indicate that the SFMBT1/HMG20A axis could be targeted to increase the resistance of CRC cells to 5-FU.

Several mechanisms have been associated with transcriptional and post-transcriptional regulation of PD-L1 in cancer. Here the authors show that a RNA binding protein, DENR, positively regulates the translation of JAK2 and induces PD-L1 expression in tumor cells, associated with immune evasion.

Objective: Self-reported sleep disturbance is common but its association with mortality has rarely been investigated.Methods: This prospective cohort analysis included 41,257 participants enrolled in the National Health and Nutrition Examination Survey from 2005 to 2018. Self-reported sleep disturbance in the present study refers to the patients who have ever consulted doctors or other professionals for trouble sleeping. Univariate and multivariate survey-weighted Cox proportional hazards models were used to evaluate the association of self-reported sleep disturbance with all-cause and disease-specific mortality.Results: Approximately 27.0% of US adults were estimated to have self-reported sleep disturbance. After adjusting for all sociodemographic variables, health behavioral factors, and common comorbidities, participants with self-reported sleep disturbance tend to have higher all-cause mortality risk with a hazard ratio (HR) of 1.17 (95% CI, 1.04–1.32) and chronic lower respiratory disease mortality risk (HR, 1.88; 95% CI, 1.26–2.80), but not cardiovascular disease mortality risk (HR, 1.19; 95% CI, 0.96–1.46) and cancer mortality risk (HR, 1.10; 95% CI, 0.90–1.35).Conclusion: Self-reported sleep disturbance could be associated with higher mortality in adults, and may need to be paid more attention in public health management.

The current status and development prospects of CCUS-EOR technology development are sorted out from the perspective of ecological development. A good foundation is laid to promote the world low-carbon development pattern and the development of CCUS-EOR technology in oil-rich, low-permeability reservoirs. By analyzing the differences between China and the United States regarding the technology level, application scale, and production effect, the development gaps between different countries in terms of CO2 burial for enhanced oil and gas recovery are derived. In response to these gaps, recommendations for responsive technology research and supporting infrastructure construction are proposed, which are of reference significance for advancing the development of large-scale CCUS technology for all of humanity.

Regulatory T (Treg) cells are important modulators of the tumor microenvironment. Here the authors perform transcriptome profiling of immune cells from patients with renal clear cell carcinoma to find a Treg signature that correlates with poorer prognosis, with CD177 being implicated as the main mediator for related alterations in Treg activity and tumor outcome.

Aiming at the problem that the current “one key sequence control” system cannot effectively carry out the test work after being deployed in a substation project, a “one key sequential control” test method based on panoramic digital simulation technology is proposed. The actual primary and secondary equipment is replaced by digital analog simulation, the instanced sequential control operation ticket is completed based on professional atlas theory, and the full logic test of the “one key sequence control” equipment status configuration library, operation ticket configuration library, operation process, error prevention logic, dual criteria, etc., is completed so as to realize the visual test of all configurations of the “one key sequence control” system. It provides an efficient and reliable technical method for the testing and acceptance of the “one key sequential control” system.

Open thoracoabdominal aortic aneurysm (TAAA) repair is a complex and challenging operation with a high incidence of serious complications, and high perioperative mortality and morbidity. Left heart bypass (LHB) is a circulatory support system used to perfuse the distal aorta during TAAA operation, and the advantages of LHB include guaranteeing distal perfusion, reducing the use of heparin, and diminishing the risk of bleeding and postoperative neurological deficits. In China, the circuit for TAAA repair is deficient, and far from the perfusion requirements. We designed a modular multifunctional LHB circuit for TAAA repair. The modular circuit consisted of cannulation pipelines, functional consumables connection pipelines, and accessory pipelines. The accessory pipelines make up lines for selective visceral perfusion and kidney perfusion, suckers and rapid infusion. The circuit can be assembled according to surgical requirements. The ultrafilter and heat exchanger are integrated into the circuit to fulfill the basic demands of LHB. The LHB circuit also has pipelines for selective visceral perfusion to the celiac artery and superior mesenteric artery and renal perfusion pipelines. Meanwhile, the reserved pipelines facilitate the quick switch from LHB to conventional cardiopulmonary bypass (CPB). The reserved pipelines reduce the time of reassembling the CPB circuit. Moreover, the rapid infusion was integrated into the LHB circuit, which can rapid infusion when massive hemorrhage during the open procedures such as exposure and reconstruction of the aorta. The ultrafiltration can diminish the consequent hemodilution of hemorrhage and rapid infusion. A hemoperfusion cartridge also can be added to reduce the systemic inflammatory during operation. The circuit can meet the needs of LHB and quickly switch to conventional CPB. No oxygenator was required during LHB, which reduce the use of heparin and reduce the risk of bleeding. The heat exchanger contributes to temperature regulation; ultrafiltration, arterial filter, and rapid-infusion facilitated the blood volume management and are useful to maintain hemodynamic stability. This circuit made the assembly of the LHB circuit more easily, and more efficient, which may contribute to the TAAA repair operation performed in lower volume centers easily. 26 patients who received TAAA repair under the modular multifunctional LHB from January 2018-March 2022 were analyzed, and we achieved acceptable clinical outcomes. The in-hospital mortality and 30-day postoperative mortality were 15.4%, and the postoperative incidences of paraparesis (4%), stroke (4%), and AKI need hemodialysis (12%) were not particularly high, based on the limited patients sample size in short research period duration.

In the past decade, dengue virus infection is one of the most prevalent and rapidly spreading arthropod-borne diseases worldwide with about 400 million infections every year. Although it has been reported that the dengue virus could take advantage of autophagy to promote its propagation, the association between selective autophagy and the dengue virus remains largely unclear. Here, we demonstrated that dengue virus capsid protein, the key viral protein for virus assembly, maturation, and replication, underwent autophagic degradation after autophagy activation. Autophagy cargo receptor p62 delivered ubiquitinated capsid protein to autophagosomes for degradation, which could be enhanced by Torin 1 treatments. Further study revealed that the association between p62 and viral capsid protein was dependent on the ubiquitin-binding domain of p62, and the poly-ubiquitin conjugated at lysine 76 of capsid protein served as a recognition signal for autophagy. Consistently, p62 deficiency in Huh7 cells led to the enhancement of dengue virus replication. Our study revealed that p62 targeted dengue virus capsid protein for autophagic degradation in a ubiquitin-dependent manner, which might uncover the potential roles of p62 in restricting dengue virus replication.

Abstract Background Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. Case presentation This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient’s condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. Conclusions When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

Abstract Background Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. Results To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. Conclusions The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases. Graphic abstract

Abstract Flexible sensors in wearable electronics have become increasingly multifunctional due to the development of materials synthesis and structure design. In particular, structural design can not only add capabilities to sensors fabricated from existing available and normal materials, but also offer opportunities for the fabrication of sensors with certain desired functions. Here, we designed a series of fiber-junction structure models, in which two fibers were simply hooked to each other to form a junction on a flexible printed circuit, for fabrication of directional bending sensors. The value and direction of bending angle are related to the change in electronic signal by a theoretical expression, allowing us to employ a simple and practicable method to use available conductive fiber materials to fabricate high-sensitivity, high-resolution and directional bending sensors. In addition, these models are generally applicable, which have broad combination with different conductive fiber, and corresponding bending sensors all possess capability of directional identification. Furthermore, the capability of identifying directional bending was demonstrated by human motion monitoring such as joint bending and muscle contraction.

Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.

Abstract Flexible sensors are required to be lightweight, compatible with the skin, sufficiently sensitive, and easily integrated to extract various kinds of body vital signs during continuous healthcare monitoring in daily life. For this, a simple and low-cost flexible temperature and force sensor that uses only two carbon fiber beams as the sensing layer is reported in this work. This simple, flexible sensor can not only monitor skin temperature changes in real time but can also extract most pulse waves, including venous waves, from most parts of the human body. A pulse diagnostic glove containing three such flexible sensors was designed to simulate pulse diagnostic methods used in traditional Chinese medicine. Wearable equipment was also designed in which four flexible sensors were fixed onto different body parts (neck, chest, armpit, and fingertip) to simultaneously monitor body temperature, carotid pulse, fingertip artery pulse, and respiratory rate. Four important physiological indicators—body temperature (BT), blood pressure (BP), heart rate (HR), and respiratory rate (RR)—were extracted by the wearable equipment and analyzed to identify exercise, excited, tired, angry, and frightened body states.

Fall event, as one of the greatest risks to the elderly, its detection has been a hot research issue in the solitary scene in recent years. Nevertheless, most current researches are conducted in the ideal environments, without considering the challenge of complex background in real situation. Therefore, this paper aims to detect fall event detection in complex background based on visual data. Different from most conventional background subtraction methods which depend on background modeling, Mask R-CNN method is first used to accurately extract the moving objects in the noise background. Then, an attention guided Bi-directional LSTM model is proposed for the final fall event detection. To demonstrate the efficiency, the proposed method is verified in the public dataset and self-build dataset. Evaluation of the algorithm performances in comparison with other state-of-the-art methods indicates that the proposed design is accurate and robust, which means it is suitable for the task of fall event detection in complex situation.

Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression.

A myocardial infarction (MI) is the leading cause of morbidity and mortality, seriously threatens human health, and becomes a major health burden of our society. It is urgent to pursue effective therapeutic strategies for the regeneration and restore myocardial function after MI. This review discusses the role of hydrogel in cardiac repair and regeneration for MI. Hydrogel-based cardiac patches and injectable hydrogels are the most commonly used applications in cardiac regeneration medicine. With injectable hydrogels, bioactive compounds and cells can be delivered in situ, promoting in situ repair and regeneration, while hydrogel-based cardiac patches reduce myocardial wall stress, which passively inhibits ventricular expansion. Hydrogel-based cardiac patches work as mechanically supportive biomaterials. In cardiac regeneration medicine, clinical trials and commercial products are limited. Biomaterials, biochemistry, and biological actives, such as intelligent hydrogels and hydrogel-based exosome patches, which may serve as an effective treatment for MI in the future, are still under development. Further investigation of clinical feasibility is warranted. We can anticipate hydrogels having immense translational potential for cardiac regeneration in the near future.

BackgroundHuman parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection.Case PresentationA 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI).ConclusionsB19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.

ObjectivesLobaplatin (LBP), a third-generation cisplatin derivative has shown promising activity and few side effects in oesophageal squamous cell carcinoma (ESCC) in previous reports. We compared LBP plus docetaxel with cisplatin plus docetaxel as adjuvant chemotherapy in ESCC patients to determine the effects on overall survival (OS) and toxicity.MethodsA multicentre retrospective study was performed using propensity score matching (PSM) with the Medicine-LinkDoc database. Patients diagnosed with stage II-III ESCC treated with adjuvant chemotherapy (cisplatin plus docetaxel or LBP plus docetaxel) between January 2013 and December 2016 were selected from 6 centres in China.ResultsThere were 733 eligible ESCC patients. After PSM (1:1 ratio), 458 patients remained. The 5-year OS rates of the cisplatin and LBP groups were 25.9% and 23.6%, respectively (P=0.457). Leukopenia (grade III-IV/I-II/0: 2.62%/34.5%/59.39% versus 5.24%/43.23%/45.85%; P=0.0176), neutropenia (grade III-IV/I-II/0: 6.55%/37.56%/51.09% versus 4.37%/53.28%/36.34%; P=0.0015), nephrotoxicity (grade I-II/0: 13.97%/76.86% versus 26.64%/65.94%; P

In this paper, a biological template method is introduced and investigated to fabricate ionic polymer-metal composite (IPMC) strain sensor with bionic hierarchical structures. We utilized the multi-level structure of reed leaf surface, which can improve the contact area between the substrate and the electrode layers. Hierarchical structures were observed on the IPMC samples, including pyramid strips with the width in the range of 60–80 μm as well as synaptic scatters with diameter around 10 μm. In addition, five kinds of sensors with different interface structures were obtained by combining the traditional microneedle roller roughening and chemical plating processes. It was found that the IPMC sensor with reed-leaf and microneedle structure on each side presented the best performance, along with a high linearity, a sensitivity of 62.5 mV/1% and a large generated voltage peak under given mechanical stimuli, which is 3.7 times that of the sample fabricated without roughening.

Summary: Organic halides (R-X) are prevalent structural motifs in pharmaceutical molecules and key building blocks for the synthesis of fine chemicals. Although a number of routes are available in the literature for the synthesis of organic halides, these methods often require stoichiometric additives or oxidants, metal catalysts, leaving or directing groups, or toxic halogenating agents. In addition, the necessity of employing different, often tailor-made, catalytic systems for each type of substrate also limits the applicability of these methods. Herein, we report a clean halogenation by electrochemical oxidation with NaX/HX. A series of organic halides were prepared under metal catalyst- and exogenous-oxidant-free reaction conditions. It is worth noting that this reaction has a broad substrate scope; various heteroarenes, arenes, alkenes, alkynes, and even aliphatic hydrocarbons could be applied. Most importantly, the reaction could also be performed on a 200-mmol scale with the same efficiency (86%, 50.9 g pure product). : Catalysis; Green Chemistry; Electrochemistry Subject Areas: Catalysis, Green Chemistry, Electrochemistry

Emerging evidence is showing that apelin plays an important role in regulating salt and water balance by counteracting the antidiuretic action of vasopressin (AVP). However, the underlying mechanism remains unknown. Here, we hypothesized that (pro) renin receptor (PRR)/soluble prorenin receptor (sPRR) might mediate the diuretic action of apelin in the distal nephron. During water deprivation (WD), the urine concentrating capability was impaired by an apelin peptide, apelin-13, accompanied by the suppression of the protein expression of aquaporin 2 (AQP2), NKCC2, PRR/sPRR, renin and nuclear β-catenin levels in the kidney. The upregulated expression of AQP2 or PRR/sPRR both induced by AVP and 8-Br-cAMP was blocked by apelin-13, PKA inhibitor (H89), or β-catenin inhibitor (ICG001). Interestingly, the blockage of apelin-13 on AVP-induced AQP2 protein expression was reversed by exogenous sPRR. Together, the present study has defined the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/sPRR pathway in the CD as the molecular target of the diuretic action of apelin.

OBJECTIVE:The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted. METHODS:A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg's funnel plots and Egger's linear regression test were used to detect any publication bias. RESULTS:This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = -1.0 min, 95% CI -1.5 to -0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001). CONCLUSION:Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.

INTRODUCTION:Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC), novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo. METHODS:We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP) under the control of the human elongation factor-1α (EF1α) promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors. RESULTS:qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67. CONCLUSION:Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

Phage-based magnetoelastic (ME) biosensors have been studied as an in-situ, real-time, wireless, direct detection method of foodborne pathogens in recent years. This paper investigates an ME biosensor method for the detection of Salmonella Typhimurium on fresh spinach leaves. A procedure to obtain a concentrated suspension of Salmonella from contaminated spinach leaves is described that is based on methods outlined in the U.S. FDA Bacteriological Analytical Manual for the detection of Salmonella on leafy green vegetables. The effects of an alternative pre-enrichment broth (LB broth vs. lactose broth), incubation time on the detection performance and negative control were investigated. In addition, different blocking agents (BSA, Casein, and Superblock) were evaluated to minimize the effect of nonspecific binding. None of the blocking agents was found to be superior to the others, or even better than none. Unblocked ME biosensors were placed directly in a concentrated suspension and allowed to bind with Salmonella cells for 30 min before measuring the resonant frequency using a surface-scanning coil detector. It was found that 7 h incubation at 37 °C in LB broth was necessary to detect an initial spike of 100 cfu/25 g S. Typhimurium on spinach leaves with a confidence level of difference greater than 95% (p < 0.05). Thus, the ME biosensor method, on both partly and fully detection, was demonstrated to be a robust and competitive method for foodborne pathogens on fresh products.

OBJECTIVE: Emergence agitation (EA) is a common complication in children under sevoflurane anesthesia. The aim of this meta-analysis was to evaluate the effects of intravenous dexmedetomidine on EA in children under sevoflurane anesthesia. METHODS: A comprehensive literature search was conducted to identify clinical trials that evaluated the effects of intravenous dexmedetomidine and placebo on EA in children under sevoflurane anesthesia. The search collected trials from MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. Analysis was conducted using STATA version 12.0. Data from each trial were pooled using relative ratio (RR) for dichotomous data or weighted mean difference (WMD) for continuous data and corresponding 95% confidence interval (95% CI). Heterogeneity assessment, sensitivity analysis, and publication bias were performed. RESULTS: Twelve trials, in which 459 patients received dexmedetomidine and 353 patients received placebo, were included in this analysis. We found that intravenous dexmedetomidine decreased the incidences of EA (RR = 0.346, 95% CI 0.263 to 0.453, P

This paper proposes a Chinese character teaching system by using the Chinese character structure theory and the 2D contour morphing technology. This system, including the offline phase and the online phase, automatically generates animation for the same Chinese character from different writing stages to intuitively show the evolution of shape and topology in the process of Chinese characters teaching. The offline phase builds the component models database for the same script and the components correspondence database for different scripts. Given two or several different scripts of the same Chinese character, the online phase firstly divides the Chinese characters into components by using the process of Chinese character parsing, and then generates the evolution animation by using the process of Chinese character morphing. Finally, two writing stages of Chinese characters, i.e., seal script and clerical script, are used in experiment to show the ability of the system. The result of the user experience study shows that the system can successfully guide students to improve the learning of Chinese characters. And the users agree that the system is interesting and can motivate them to learn.

MiR-145 could regulate tumor growth, apoptosis, migration, and invasion. In our present study, we investigated its role in epithelial-mesenchymal transition (EMT). Expression of miR-145 was decreased in breast tumor tissues at T3&4 stages in comparison with those at T1&2. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and dampened those of α-SMA and Fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited Oct4 expression and miR-145 inhibitor enhanced it. Over-expression of Oct4 reversed miR-145-regulated expression of EMT markers, suggesting that Oct4 mediated the inhibitory effects of miR-145. MiR-145 could inhibite the expression of Snail, ZEB1, and ZEB2, while over-expression of Oct4 rescued the effects. Furthermore, Oct-4 induced over-expression of transcription factor Snail, ZEB1 and ZEB2 was mediated by β-catenin. Expression of Slug and Twist were not altered by miR-145/Oct4. Taken together, our results have revealed a novel role of miR-145 on EMT. It inhibits EMT by blocking the expression of Oct4, and downstream transcriptional factors, Snail, ZEB1 and ZEB2.

BACKGROUND: The gene encoding CD14 has been proposed as an IBD-susceptibility gene with its polymorphism C-260T being widely evaluated, yet with conflicting results. The aim of this study was to investigate the association between this polymorphism and IBD by conducting a meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen articles met the inclusion criteria, which included a total of 18 case-control studies, including 1900 ulcerative colitis (UC) cases, 2535 Crohn's disease (CD) cases, and 4004 controls. Data were analyzed using STATA software. Overall, association between C-260T polymorphism and increased UC risk was significant in allelic comparison (odds ratio [OR] =1.21, 95% confidence interval [CI]: 1.02-1.43; P=0.027), homozygote model (OR =1.44, 95% CI: 1.03-2.01; P=0.033), as well as dominant model (OR =1.36, 95% CI: 1.06-1.75; P=0.016). However, there was negative association between this polymorphism and CD risk across all genetic models. Subgroup analyses by ethnicity suggested the risk-conferring profiles of -260T allele and -260 TT genotype with UC in Asians, but not in Caucasians. There was a low probability of publication bias. CONCLUSIONS/SIGNIFICANCE: Expanding previous results of individual studies, our findings demonstrated that CD14 gene C-260T polymorphism might be a promising candidate marker in susceptibility to UC, especially in Asians.

Controlling large-wavelength acoustic waves via small-size structures is an important direction for the field of noise control. Since porous acoustic material can only absorb low-frequency sound waves when their thickness is approximately one-fourth of the wavelength, such acoustic material is not effective when controlling the large wave length acoustic waves with small-size structures. Therefore, the resonant acoustic material has been usually chosen to absorb low-frequency sound waves instead. As a typical resonant acoustic material, microperforated plate structures (MPPS), need one large cavity with low space utilization to absorb the low-frequency acoustic waves. The microperforated plate-labyrinth coupled structure (MPPS-LS) has been proposed with the goal of improving low-frequency sound absorption ability, which is consisted of a MPPS and three separated second-order LS coupled together. The mathematical model has been established using the acousto-electric analogy method and transfer matrix method to examine the impact of the structural parameters of each part on the acoustic characteristics. According to this study, the coupled structure is compact in size and has a good low and medium-frequency acoustic absorption effect, combining low and medium-frequency acoustic absorption characteristics of both the MPPS and LS. The sound absorption of the structure after optimized design is testing using impedance tube. [ABSTRACT FROM AUTHOR]

Background: von Willebrand disease (vWD), caused by mutations in the von Willebrand factor (vWF) coding gene, is a disease characterized by abnormal coagulation activity and a severe tendency for hemorrhage. Therefore, identifying mutations in vWF is important for diagnosing congenital vWD. Methods: We studied a 23-year-old male vWD patient and his parents. Clotting methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB) levels, FVIII activity. Chromogenic substrate method was used to determine vWF antigen and activity. The platelet count was determined. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Clinical data, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, FX antigen levels, and the platelet count were collected. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulants. Mutations were screened by using whole-exome sequencing (WES) and were verified by using Sanger sequencing. Results: The proband showed severely decreased vWF antigen, vWF activity, and FVIII activity. RIPA (RISTOCETIN-induced platelet aggregation) was 0%. Data from WES showed that the proband carried compound heterozygous variants vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) and vWF: NM_000552.5 (c.6598+2T>C). The proband's mother carried variant vWF: NM_000552.5 (c.3213C>A p.Cys1071Ter) while the proband's father carried variant vWF: NM_000552.5 (c.6598+2T>C). All laboratory test indexes of the proband's parents, including vWF antigen, vWF activity, and FVIII activity, were within the normal ranges. Conclusions: We identified a compound heterozygosis with two novel mutations in vWF (c.3213C>A, c.6598+2T >C) in a family pedigree, and our results demonstrate that the compound heterozygous mutations probably exacerbate vWD. [ABSTRACT FROM AUTHOR]