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Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs. Many studies have revealed translational regulation in plants in response to various environmental stimuli. However, there have been no studies documenting the comprehensive landscape of translational regulation and allele-specific translational efficiency in multiple plant tissues, especially those of rice, a main staple crop that feeds nearly half of the world's population. Here we used RNA sequencing and ribosome profiling data to analyze the transcriptome and translatome of an elite hybrid rice, Shanyou 63 (SY63), and its parental varieties Zhenshan 97 and Minghui 63. The results revealed that gene expression patterns varied more among tissues than among varieties at the transcriptional and translational levels. We identified 3392 upstream open reading frames (uORFs), and the uORF-containing genes were enriched in transcription factors. Only 668 of 13 492 long non-coding RNAs could be translated into peptides. Finally, we discovered numerous genes with allele-specific translational efficiency in SY63 and demonstrated that some cis-regulatory elements may contribute to allelic divergence in translational efficiency. Overall, these findings may improve our understanding of translational regulation in rice and provide information for molecular breeding research., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To develop and validate an easy-to-use scoring system to predict the response to the first epidural blood patching in patients with spontaneous intracranial hypotension., Methods: This study recruited consecutive patients with spontaneous intracranial hypotension receiving epidural blood patching in a tertiary medical center, which were chronologically divided into a derivation cohort and a validation cohort. In the derivation cohort, factors associated with the first epidural blood patching response were identified by using multivariable logistic regression modeling. A scoring system was developed, and the cutoff score was determined by using the receiver operating characteristic curve. The findings were verified in an independent validation cohort., Results: The study involved 280 patients in the derivation cohort and 78 patients in the validation cohort. The spontaneous intracranial hypotension-epidural blood patching score (range 0-5) included two clinical variables (sex and age) and two radiological variables (midbrain-pons angle and anterior epidural cerebrospinal fluid collections). A score of ≥3 was predictive of the first epidural blood patching response, which was consistent in the validation cohort. Overall, patients who scored ≥3 were more likely to respond to the first epidural blood patching (odds ratio = 10.3)., Conclusion: For patients with spontaneous intracranial hypotension-epidural blood patching score ≥3, it is prudent to attempt at least one targeted epidural blood patching before considering more invasive interventions.

The Pacific Ocean plays an important role in regulating the budget of climatically active gases and the burden of sulfate aerosols. Here, a field investigation was conducted to clarify the key processes and factors controlling climatically active gases, including dimethyl sulfide (DMS), carbonyl sulfide (OCS), carbon disulfide (CS 2 ), and carbon dioxide (CO 2 ), in both surface seawater and the lower atmosphere of the western Pacific. In addition, the relative contributions of different sources to atmospheric sulfate aerosols were quantitatively estimated, and their causes were explored. The maximum concentrations of DMS, OCS and CS 2 and the minimum partial pressure of CO 2 (pCO 2 ) were observed in the Kuroshio-Oyashio Extension. Kuroshio-induced mesoscale eddies brought abundant nutrients and organic matter from the subsurface layer of Oyashio into the euphotic layer, thus enhancing primary productivity and accelerating the photoreaction of organic matter. These processes led to higher concentrations of DMS, OCS and CS 2 and lower pCO 2 . However, the oligotrophic subsurface layer in the subtropical gyre and the strong barrier layer in the equatorial waters suppressed the upward fluxes of nutrients and organic matter, resulting in lower surface concentrations of DMS, OCS, and CS 2 in these areas. Being far from the continents, atmospheric concentrations of DMS, OCS and CS 2 and pCO 2 in the western Pacific generally were observed to depend on the local sea-to-air exchange and may be regulated by atmospheric oxidation and mixing of air masses. In general, oceanic DMS emissions played an important role in the formation of sulfate aerosols in the western Pacific (accounting for ∼19.5% of total sulfate aerosols), especially in the Kuroshio-Oyashio Extension (∼32.3%). These processes in seawater may also determine the variations and emissions of other climatically active gases from biogenic and photochemical sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To investigate the relationship between auditory pathway function and cochlear size in deaf children with a radiologically normal inner ear or Mondini malformation., Methods: Thirty-five deaf children without inner ear malformations (IEMs) and forty cases with Mondini malformation were included in this study. The electrically evoked auditory brainstem responses (EABRs) evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded during cochlear implantation (CI) surgery. The anatomical parameters of the cochlea were assessed by high-resolution computed tomography and OTOPLAN 3-D construction software. Correlations between EABRs and cochlear sizes were analyzed., Results: The EABR thresholds and/or latencies were negatively correlated with the basal cochlear diameter, cochlear width and/or cochlear duct length in both patients without IEMs and those with Mondini malformation., Conclusion: The physiological function of the peripheral auditory system depends on the anatomical structure of the cochlea to an extent. A larger cochlear size appears to be associated with better auditory conduction function. Our findings may be beneficial to selection of the proper electrode type and prediction of postoperative auditory rehabilitation., Level of Evidence: Level 4., Competing Interests: The authors have no other funding, financial relationships, or conflicts of interest to disclose., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

The presence of more species in the community of a sampling site (α diversity) typically increases ecosystem functions via nonrandom processes like resource partitioning. When considering multiple communities, we hypothesize that higher compositional difference (β diversity) increases overall functions of these communities. Further, we hypothesize that the β diversity effect is more positive when β diversity is increased by nonrandom assembly processes. To test these hypotheses, we collected bacterioplankton along a transect of 6 sampling sites in the southern East China Sea in 14 cruises. For any pairs of the 6 sites within a cruise, we calculated the Bray-Curtis index to represent β diversity and summed bacterial biomass as a proxy to indicate the overall function of the two communities. We then calculated deviation of observed mean pairwise phylogenetic similarities among species in two communities from random to represent the influences of nonrandom processes. The bacterial β diversity was found to positively affect the summed bacterial biomass; however, the effect varied among cruises. Cross-cruise comparison indicated that the β diversity effect increased with the nonrandom processes selecting for phylogenetically dissimilar species. This study extends biodiversity-ecosystem functioning research to the scale of multiple sites and enriches the framework by considering community assembly processes. IMPORTANCE The implications of our analyses are twofold. First, we emphasize the importance of studying β diversity. We expanded the current biodiversity-ecosystem functioning framework from single to multiple sampling sites and investigated the influences of species compositional differences among sites on the overall functioning of these sites. Since natural ecological communities never exist alone, our analyses allow us to more holistically perceive the role of biodiversity in natural ecosystems. Second, we took community assembly processes into account to attain a more mechanistic understanding of the impacts of biodiversity on ecosystem functioning.

Background: Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell-cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited., Methods: Intercellular communications were characterized by single-cell data. Firstly, we employed "CellChat" package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort., Results: Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell-cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency., Conclusions: The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC., (© 2023. The Author(s).)

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient., Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months., Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO 2 ) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO 2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO 2 (P[A-a]O 2 ), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months., Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO 2 , predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis., Trial Registration: ClinicalTrial.gov, identifier: NCT04516577., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Huang, Shi, Ge, Lu, Sun, Gu, Liang, Cheng, Tian, Xiao, Xu and Xu.)

Lipids establish the specialized thylakoid membrane of chloroplast in eukaryotic photosynthetic organisms, while the molecular basis of lipid transfer from other organelles to chloroplast remains further elucidation. Here we revealed the structural basis of Arabidopsis Sec14 homology proteins AtSFH5 and AtSFH7 in transferring phosphatidic acid (PA) from endoplasmic reticulum (ER) to chloroplast, and whose function in regulating the lipid composition of chloroplast and thylakoid development. AtSFH5 and AtSFH7 localize at both ER and chloroplast, whose deficiency resulted in an abnormal chloroplast structure and a decreased thickness of stacked thylakoid membranes. We demonstrated that AtSFH5, but not yeast and human Sec14 proteins, could specifically recognize and transfer PA in vitro. Crystal structures of the AtSFH5-Sec14 domain in complex with L-α-phosphatidic acid (L-α-PA) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) revealed that two PA ligands nestled in the central cavity with different configurations, elucidating the specific binding mode of PA to AtSFH5, different from the reported phosphatidylethanolamine (PE)/phosphatidylcholine (PC)/phosphatidylinositol (PI) binding modes. Quantitative lipidomic analysis of chloroplast lipids showed that PA and monogalactosyldiacylglycerol (MGDG), particularly the C18 fatty acids at sn -2 position in MGDG were significantly decreased, indicating a disrupted ER-to-plastid (chloroplast) lipid transfer, under deficiency of AtSFH5 and AtSFH7. Our studies identified the role and elucidated the structural basis of plant SFH proteins in transferring PA between organelles, and suggested a model for ER-chloroplast interorganelle phospholipid transport from inherent ER to chloroplast derived from endosymbiosis of a cyanobacteriumproviding a mechanism involved in the adaptive evolution of cellular plastids.

The abnormal expression of chordin-like 1 (CHRDL1) is identified in many cancers, while the effect of CHRDL1 in thyroid cancer (THCA) remains unclear. The University of California Santa Cruz, Gene Expression Profiling Interactive Analysis, University of Alabama at Birmingham Cancer, and Gene Expression Omnibus database (GSE33570, GSE33630, and GSE60542) were used for determining the mRNA and methylation expression of CHRDL1 in tumor and normal tissues. Human Protein Atlas was used for exploring the protein expression level of CHRDL1. The genes correlated to CHRDL1 were assessed by cBioPortal database. The prognostic value of CHRDL1 was evaluated through Kaplan-Meier method, cox regression, and nomogram analysis. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis were used for predicting potential function of CHRDL1. The relationship between CHRDL1 and immune cell infiltration was determined by Pearson method. The downregulated mRNA and protein expressions of CHRDL1 were identified in THCA through the analysis of data from The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas database. The survival analysis showed that the CHRDL1 expression significantly affected disease-free interval (DFI) and progression-free interval, and CHRDL1 was an independent predictor of DFI. Besides, we found that C-C motif chemokine ligand 21 could significantly affect DFI time when it was co-expressed with CHRDL1. Additionally, the function of CHRDL1 was enriched in cell migration, apoptosis, and immune cell receptor. The downregulated expression of CHRDL1 was observed in THCA and caused poor prognosis. CHRDL1 may be involved in signal pathway related to cancer development and immune response, which suggested it could be a potential biomarker., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: We aimed to reveal the 5-year clinical outcomes of 3-dimensional (3D) interstitial high-dose-rate (HDR) brachytherapy with regional metastatic lymph node intensity modulated radiation therapy (IMRT) for locally advanced peripheral non-small cell lung cancer (NSCLC), which has been shown to have low toxicity and improved 2-year survival rates in patients with this disease., Methods and Materials: In this phase 2, single-arm, open-label clinical trial, 83 patients with locally advanced peripheral NSCLC were enrolled (median follow-up [range], 53.7 [4.3-120.4] months). All eligible patients received 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT. The primary endpoint was overall survival (OS). Secondary endpoints were local recurrence-free survival, regional recurrence-free survival, progression-free survival, distant metastasis-free survival, toxicities, and quality of life., Results: The final analysis included 75 patients (19 [25.3%] females, 56 [74.7%] males; median [range] age, 64 [44-80] years; stage IIIA, 34 [45.3%]; stage IIIB, 41 [54.7%]). At the latest follow-up, 32 (42.7%) patients had survived. The median OS was 38.0 months (5-year OS, 44.5%; 95% confidence interval [CI], 33.8%-58.6%). Local recurrence-free survival, recurrence-free survival, and distant metastasis-free survival at 5 years were 79.2% (95% CI, 68.5%-91.5%), 73.6% (95% CI, 61.5%-88.1%), and 50.3% (95% CI, 38.3%-66.1%), respectively. The dominant failure pattern was distant disease, corresponding to 40% (30 of 75) of patients and 65.2% (30 of 46) of all failures. Two (2.7%) patients developed grade 1 acute pneumonitis. Grade 2 and 3 acute esophagitis occurred in 11 (14.7%) and 4 (5.3%) patients, respectively. No late radiation-related grade ≥2 late adverse events were observed., Conclusions: 3D interstitial HDR brachytherapy with regional metastatic lymph node IMRT for locally advanced peripheral NSCLC shows significant OS and has a low toxicity rate. Additional evaluation in a phase 3 trial is recommended to substantiate these findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Polysulfamides are the -SO 2 - analogues of polyureas and form an intriguing family of polymers containing hydrogen-bond donor and acceptor groups. However, unlike polyureas, their physical properties are mostly unknown because of the scarcity of synthetic methods to access such polymers. Herein, we report an expedient synthesis of AB monomers for the synthesis of polysulfamides via Sulfur(VI) Fluoride Exchange (SuFEx) click polymerization. Upon optimization of the step-growth process, a variety of polysulfamides were isolated and characterized. The versatility of the SuFEx polymerization allowed structural modulation of the main chain through the incorporation of aliphatic or aromatic amines. While all synthesized polymers presented high thermal stability via thermogravimetric analysis, the glass-transition temperature and crystallinity were shown to be highly tied to the structure of the backbone between repeating sulfamide units through differential scanning calorimetry and powder X-ray diffraction. Careful analysis via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and X-ray crystallography also revealed the formation of macrocyclic oligomers during the polymerization of one AB monomer. Finally, two protocols were developed to efficiently degrade all synthesized polysulfamides through either chemical recycling for polymers derived from aromatic amines or oxidative upcycling for those based on aliphatic amines., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Sphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles., Methods: We prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0-5) were recorded to analyze their association with SPG volume., Results: The inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84-0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] μL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] μL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066)., Conclusions: This proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH., (© 2022. The Author(s).)

In 1945, atomic bombs were dropped on Hiroshima and Nagasaki. Approximately 70 000 Koreans are estimated to have been exposed to radiation from atomic bombs at that time. After Korea's Liberation Day, approximately 23 000 of these people returned to Korea. To investigate the long-term health and hereditary effects of atomic bomb exposure on the offspring, cohort studies have been conducted on atomic bomb survivors in Japan. This study is an ongoing cohort study to determine the health status of Korean atomic bomb survivors and investigate whether any health effects were inherited by their offspring. Atomic bomb survivors are defined by the Special Act On the Support for Korean Atomic Bomb Victims, and their offspring are identified by participating atomic bomb survivors. As of 2024, we plan to recruit 1500 atomic bomb survivors and their offspring, including 200 trios with more than 300 people. Questionnaires regarding socio-demographic factors, health behaviors, past medical history, laboratory tests, and pedigree information comprise the data collected to minimize survival bias. For the 200 trios, whole-genome analysis is planned to identify de novo mutations in atomic bomb survivors and to compare the prevalence of de novo mutations with trios in the general population. Active follow-up based on telephone surveys and passive follow-up with linkage to the Korean Red Cross, National Health Insurance Service, death registry, and Korea Central Cancer Registry data are ongoing. By combining pedigree information with the findings of trio-based whole-genome analysis, the results will elucidate the hereditary health effects of atomic bomb exposure.

Background: Posterior approach pedicle screw fixation without fusion is widely used in the treatment of neurologically intact type A3 thoracolumbar fractures., Objective: To analyze the influence of the facet joint (FJ) angle on FJ degeneration following posterior approach pedicle screw fixation without fusion in neurologically intact type A3 thoracolumbar fractures., Methods: Fifty-eight patients who underwent pedicle screw fixation via the traditional posterior approach (n= 28) or the Wiltse approach (n= 30) were enrolled. A CT scan was performed before fixation and before fixation removal (Within 1.5 to 2 years after fixation) to evaluate the FJs parameters, including FJ inclination (FJI), FJ tropism (FJT), FJ violation, and FJ degeneration grade (FJDG), of three fixed segments and the adjacent segment below the fixed segments., Results: There was no significant difference in FJ violation rate, FJDG deterioration, or FJ angle between the two groups (P> 0.05). FJDG deterioration showed a weak positive correlation with FJI and FJT before fixation, and the angular change in FJI (P< 0.05); and FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration (P< 0.01)., Conclusion: The Wiltse approach did not increase the rate of FJDG deterioration and FJs angle changes. However, the FJT before fixation and the angular change in FJI were risk factors for FJDG deterioration.

During development of the cerebral cortex, neuroepithelial and radial glial cells undergo an oscillatory nuclear movement throughout their cell cycle, termed interkinetic nuclear migration. The nucleus of postmitotic neurons derived from these neural stem cells also translocates in a saltatory manner to enable neuronal migration toward the cortical plate. In these processes, various molecular motors, including cytoplasmic dynein, myosin II, and kinesins, are the driving force for nuclear migration at different stages. Despite efforts made to understand the mechanism regulating cortical development over decades, novel gene mutations discovered in neurodevelopmental disorders indicate that missing pieces still remain. Gene manipulation by in utero electroporation combined with live microscopy of neural stem cells in brain slices provides a powerful method to capture their detailed behaviors during proliferation and migration. The procedures described in this chapter enable the monitoring of cell cycle progression, mitosis, morphological changes, and migratory patterns in situ. This approach facilitates the elucidation of gene functions in cortical development and neurodevelopmental disorders., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD., Competing Interests: None

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP. In the present study, we found that Cx43 deletion significantly ameliorated spared nerve injury (SNI)-induced NP and suppressed SNI induced c-Fos expression in the spinal cord. Notably, Cx43 deletion led to much less SNI-induced microglia activation in the spinal cord. These results suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Type 2 diabetes mellitus (T2DM) is a huge challenge for global public health systems. Currently, healthcare policies advocate the prevention of the onset and progression of T2DM by improving individual lifestyles. The increasing benefits of intermittent fasting (IF) as a dietary intervention have been elucidated. However, the beneficial effects of IF in T2DM remain inconclusive. We demonstrated the physiological mechanisms underlying the positive effects of IF in T2DM. IF could trigger metabolic transformation to improve systemic metabolism and induce tissue-specific metabolic adaptations through alterations in the gut microbiota, adipose tissue remodeling, correction of circadian rhythm disturbances, and increased autophagy in peripheral tissues. The efficacy and safety of IF regimens in clinical applications carry a risk of hypoglycemia and require monitoring of blood glucose and timely adjustment of medications. However, there is limited evidence of a positive effect of IF in weight loss and improvement of glycemic variables. Overall, IF serves as a promising therapeutic target for T2DM and needs to be established by a large randomized controlled trial.

Networks are powerful tools to uncover functional roles of genes in phenotypic variation at a system-wide scale. Here, we constructed a maize network map that contains the genomic, transcriptomic, translatomic and proteomic networks across maize development. This map comprises over 2.8 million edges in more than 1,400 functional subnetworks, demonstrating an extensive network divergence of duplicated genes. We applied this map to identify factors regulating flowering time and identified 2,651 genes enriched in eight subnetworks. We validated the functions of 20 genes, including 18 with previously unknown connections to flowering time in maize. Furthermore, we uncovered a flowering pathway involving histone modification. The multi-omics integrative network map illustrates the principles of how molecular networks connect different types of genes and potential pathways to map a genome-wide functional landscape in maize, which should be applicable in a wide range of species., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Harvesting light by metallic structures with sharp corners, or the so-called photonic singularities, has exhibit their potential in nanophotonics, sensing, and bio-medical applications. The high-quality light confinement of the light energy mainly relies on the precise preparation of nanoscale photonic singularities. However, the realization of massive photonic singularities still meets the challenges on integration and low-cost mask multiplexing. Here, we show an angle-dependent elevated nanosphere lithography to achieve massive photonic singularities for spatially modulated light harvesting at the near-infrared regime. The photonic geometrical singularity is constructed by the gold crescent array of plasmonic materials. The numerical simulation shows that the light can be localized at the spatially distributed singularities. This phenomenon is verified experimentally through the infrared spectral measurement. Our work provides the possibility to produce integrated light-harvesting devices for numerous optical applications in illumination, display, and enhanced nonlinear excitation.

In this paper, the fluorescence quenching characteristics of Au-Ag-Pt core-shell nanorods have been studied.Due to nonradiative energy transformation, the fluorescence emission intensity of bovine serum albumin (BSA) could be greatly quenched.It has been found that the quenching effect of Au-Ag-Pt core-shell nanorods could be optimized by adjusting the concentration of chloroplatinic acid.Based on the fluorescence quenching properties of Au-Ag-Pt core-shell nanorods, Au-Ag-Pt trimetal fluorescence quenching nanoprobe has been prepared, and the specificity of alpha-fetoprotein (AFP) detection has also been realized.In order to guarantee the sensing specificity, the surface modification including carboxyl replacement, carboxyl activation and antibody connection have been performed on Au-Ag-Pt core-shell nanorods.By using the principle of specific combination of antigen and antibody, the specific detection of AFP has been realized with a lower detection limit of 4.0 pg/mL, and the linear detection range spans a scope from 0.03 to 0.5 ng/mL.Interference experiments and the actual samples detection results show that the Au-Ag-Pt trimetal core-shell nanorod probes have good anti-interference and repeatability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To compare the clinical profiles between male and female cluster headache patients from a large cohort., Methods: This hospital-based study enrolled patients diagnosed with cluster headache between 1997 to 2021. Participants completed structured questionnaires collecting information on demographics, clinical profiles, and quality of life. Treatment regimens and effectiveness were determined through medical chart review. All variables were compared between the sexes., Results: In total, 798 patients (M/F:659/139) were enrolled. The male-to-female ratio was 4.7:1 for the full study period, but it declined from 5.2:1 to 4.3:1 for patients enrolled before and after 2010, respectively. The frequencies of chronic cluster headache (M:1.2%, F:1.4%) and aura (M:0.3%, F:0.7%) were low but similar between the sexes. Most headache features showed no difference between men and women. Female patients had significantly longer attack duration, shorter inter-bout duration, higher frequencies for eyelid edema, nausea and vomiting and lower frequencies for conjunctival injection and pacing. Sex difference did not influence headache-associated disability, anxiety, or depression, but poor sleep quality was significantly more common in women. Among menstruating women, 22/122 (18.0%) reported worsening headaches during menses. The effectiveness of treatment was similar between the sexes., Conclusions: Despite a decline of male-to-female ratio in the past two decades, most clinical profiles were similar between the sexes.

Platinum-based chemotherapy drugs play a very important role in the treatment of patients with advanced colorectal cancer, but the drug resistance of platinum-based chemotherapy drugs is an important topic that puzzles us. If we can find mechanisms of resistance, it will be revolutionary for us. We analysed the differential genes, core genes and their enrichment pathways in platinum-resistant and non-resistant patients through a public database. Platinum-resistant cell lines were cultured in vitro for in vitro colony and Transwell analysis. Tumorigenesis analysis of nude mice in vivo. Verify the function of core genes. Through differential gene and enrichment analysis, we found that CUL4B was the main factor affecting platinum drug resistance and EMT. Our hypothesis was further verified by in vitro drug-resistant and wild-type cell lines and in vivo tumorigenesis analysis of nude mice. CUL4B leads to platinum drug resistance in colorectal cancer by affecting tumour EMT., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor (TF) SpiC with these cells. Single-cell RNA sequencing (scRNA-Seq) showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression of Timd4 and Cx3cr1 . Remarkably, Timd4 + cells were located in the cortex, while Cx3cr1 + macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins. Timd4 + thymic macrophages are of embryonic origin, while Cx3cr1 + macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus. Timd4 + cells underwent gradual attrition, while Cx3cr1 + cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages., Competing Interests: TZ, HH, YT, HC, CL, NC, JT, ER, HH, CH, ID No competing interests declared, (© 2022, Zhou et al.)

Plasmonic core-satellite nanostructures assembled from simple building blocks have attracted extensive attention since they were reported by the way of DNA-directed assembly in 1998, because of their unique enhanced and synergistic optical properties and widespread potential applications in biosensing, imaging, drug delivery, and diagnostics. In this review, we introduce the synthetic methods of core-satellite nanostructures, emphazising the bottom-up synthesis method, including DNA, molecular, protein, peptide, amino acids, metal ion-assisted assembly, electrostatic adsorption assembly, clicked-to-assembly, and in situ deposition. Than we review and discuss their morphology classification, and summarize influencing factors of morphology. This is followed by overviews on optical properties, including localized surface plasmon resonance, surface-enhanced Raman scattering, surface-enhanced fluorescence and quenching, and applications in the biomedical field. Finally, the challenges and prospects of these kinds of nanostructures are discussed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis., Methods: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31)., Results: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites., Conclusion: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis., Trial Registration:  This study is registered with ClinicalTrials.gov, number NCT04490447., (© 2022. The Author(s).)

A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT 1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC 50  = 8.2 nM) and marked 5-HT 1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The photooxygenation of amyloid-β (Aβ) protein is considered a promising strategy against Alzheimer's disease (AD). The inhibition of Aβ aggregation or depolymerization of Aβ aggregates can effectively alleviate and improve the condition of AD. Herein, we report a series of "off-on" near-infrared quinolinium photosensitizers (QM20-QM22) based on D-π-A structures using a target-sensing catalyst activation (TaSCAc) strategy. They exhibit turn-on fluorescence when bonded to Aβ aggregates and generate singlet oxygen to achieve the specific imaging and photooxygenation of Aβ aggregates, leading to attenuated Aβ aggregates, enhancing their clearance through the microglial lysosomal pathway, decreasing their neurotoxicity. This study will shed light on the development of the photooxygenation of misfolded proteins for the treatment of neurodegenerative diseases.

Purpose: To compare the effectiveness and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab with those of TACE as well as apatinib among patients with unresectable hepatocellular carcinoma (HCC)., Materials and Methods: The data of patients with unresectable HCC (uHCC) who received TACE-apatinib-camrelizumab combination (TACE + AC group) and TACE-apatinib combination (TACE + A group) were collected from two centers between January 2018 and January 2022. Propensity score matching (PSM) was conducted to diminish the bias between the two groups. The primary outcome measures of the study were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were response rate (ORR), disease control rate (DCR), and adverse events (AEs)., Results: A total of 102 patients were enrolled in this study after PSM, with 34 patients in the TACE + AC group and 68 patients in the TACE + A group. Compared to the TACE + A group, TACE + AC had a significantly longer median OS (25.5 months, interquartile range [IQR], 23.5-33.0) than 18.5 months (IQR, 13.0-25.0; P = 0.001). Similarly, the PFS of the TACE + AC group was significantly improved (14.0 months, IQR, 9.0-NA) compared to that of the TACE + A group (5.0 months, IQR, 2.5-9.0; P = 0.001). The ORR rates (55.9% vs. 51.5%), and DCR rates (79.4% vs. 72.1%) were comparable between groups ( P > 0.05). All treatment-related adverse events were tolerable and manageable, and no serious adverse events were observed., Conclusion: TACE combined with apatinib plus camrelizumab demonstrated superior efficacy to TACE plus apatinib for patients with unresectable HCC. The two combination therapies showed similar safety profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Ma, Yang, Zhou, Shi, Ren, Xie, Liu, Shi and Zhou.)

Microglia play a crucial role in the activation of immune defense mechanism as the resident macrophages in the central nervous system (CNS). Microglia can eliminate damaged neurons, plaques, and other infectious agents. Triggering receptor expressed on myeloid cell-2 (TREM-2) speculates to be beneficial in preventing inflammation-induced bystander damage of neurons. However, the precise molecular mechanisms underlying the regulation of TREM-2 on neurons are not clarified. We cultured PC12 cells with conditioned medium which was the supernatant of LPS-treated BV2 cells and six groups of PC12 cells (control group, LPS group, TREM-2 WT + LPS group, TREM-2 over-expression + LPS group, siRNA control + LPS group, and siRNA TREM-2 + LPS group) were investigated. The mRNA levels of inflammatory mediators: Nitric oxide synthase (iNOS) and Arginase-1(Arg-1) were quantified by using RT-PCR. Assessment of apoptosis in PC12 cells mediated by BV2 microglia was analyzed using TUNEL assays. The result showed that LPS stimulation significantly enhanced inducible iNOS (M1) production in BV2 cells (P < 0.01), and increased PC12 cells apoptosis (P < 0.01), while reduced the production of Arg-1 (M2) in BV2 cells (P < 0.01). These effects were attenuated by TREM-2 over-expression, but enhanced by TREM-2 silencing. It indicated that TREM-2 inhibited LPS-mediated neuronal apoptosis by down-regulating iNOS and up-regulating the expression of Arg-1 in BV2 microglia. Therefore, our findings may provide new insights in the regulation of TREM-2 on neuronal apoptosis via BV2 microglial M1/M2 modulation., Competing Interests: None

Abstract: Tolterodine is a first-line antimuscarinic drug used to treat overactive bladder. Adverse cardiac effects including tachycardia and palpitations have been observed, presumably because of its inhibition of the human ether-à-go-go-related gene (hERG) K + channel. However, the molecular mechanism of hERG channel inhibition by tolterodine is largely unclear. In this study, we performed molecular docking to identify potential binding sites of tolterodine in hERG channel, and two-microelectrode voltage-clamp to record the currents of hERG and its mutants expressed in Xenopus oocytes. The results of computational modeling demonstrated that phenylalanine at position 656 (F656) and tyrosine at position 652 (Y652) on the S6 helix of hERG channel are the most favorable binding residues of tolterodine, which was validated by electrophysiological recordings on Y652A and F656A hERG mutants. The Y652A and F656A mutations decreased inhibitory potency of tolterodine 345-fold and 126-fold, respectively. The Y652A mutation significantly altered the voltage dependence of channel inhibition by tolterodine. For both the wild-type and the mutant channels, tolterodine reduced the currents in a time-dependent manner, and the blockade occurred with the channel activated. Tolterodine did not interfere with hERG channel deactivation, whereas channel inactivation greatly impaired its blocking effect. The inhibition of hERG channel by tolterodine is independent of its action on muscarinic acetylcholine receptors. In conclusion, tolterodine is an open-state blocker of hERG K + channel with nanomolar potency. Y652 and F656, 2 aromatic residues on the inner S6 helix, are responsible for the high-affinity binding of tolterodine to hERG channel., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In this paper, a novel Au@AuAg yolk-shell heterogeneous nanostructure is designed as plasmonic spectroscopic sensor based on surface etching for ultrasensitive detection of trace cobalt ions (Co 2+ ). Due to the surface diffusion of gold atoms, the Ag at one end of the core gold nanobipyramids (Au NBPs) is retained, and Au@AuAg yolk-shell nanostructure with asymmetric core is prepared. The alloy shell is coupled to Au NBPs and the interface of asymmetric Ag respectively, the two local surface plasmon resonance bands will have obvious reverse changes depending on the surface morphology of the shell. By using this distinct plasmon response generated by Co 2+ induced surface etching, which is driven by discrepancy of double-peaks, a sensing method has been established to realize multi-information spectral detection of Co 2+ . There is a good linear relationship between the intensity ratio and the Co 2+ concentration in the range of 1-100 nM, in which the limit of detection is 0.2 nM. This method further improves the sensing capability by combining multiple pieces of strongly changing spectral information, and demonstrates great advantages and potential of Au@AuAg yolk-shell heterogeneous nanostructure as a multi-information plasmonic sensor based on etched shell surface for trace detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe ( 1 ) with a rotatable meso- benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso -benzothiazole group. The intensity (log I 534 ) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso -benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.

Aims: Vascular peroxidase 1 (VPO1) plays an important role in mediation of vascular remodeling with pulmonary arterial hypertension (PAH). This study aims to determine whether VPO1 can promote phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) and the underlying mechanisms., Main Methods: Sprague-Dawley (SD) rats were exposed to 10 % O 2 for 21 days to establish the model of vascular remodeling in pulmonary arterial hypertension. PASMCs were incubated with 3 % O 2 for 48 h to induce phenotypic transformation. Western blot was performed to detect the expressions of target proteins. The 5-ethynyl-2'-deoxyuridine (EdU) assay was conducted to measure the proliferation of PASMCs., Key Findings: In the rats exposed to hypoxia, there were increases in right ventricular systolic pressure, pulmonary vascular remodeling and phenotypic transformation of PASMCs (the down-regulated contractile proteins of α-smooth muscle actin, smooth muscle 22α while the up-regulated synthetic proteins of osteopontin, cyclinD1), accompanied by up-regulation of VPO1, increase of hypochlorous acid (HOCl) production and elevation of the phosphorylation of ERK. In the cultured PASMCs exposed to hypoxia, similar results were achieved but they were reversed by VPO1 small interfering RNA (VPO1 siRNA) or HOCl inhibitor. Replacement of hypoxia with NaOCl could induce PASMCs phenotypic transformation and activate the ERK signaling. Furthermore, ERK inhibitor (PD98059) could also attenuate hypoxia-induced PASMCs phenotypic transformation., Significance: VPO1 play a pivotal role in promotion of phenotypic transformation of PASMCs under hypoxic condition through activation of VPO1/HOCl/ERK pathway. It might serve as a potential target for prevention of pulmonary vascular remodeling., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

The eutrophication of coastal water has been a critical environmental problem in China's offshore areas. How to effectively assess the status of coastal waters is key for pollution treatment and environmental protection. In recent years, eutrophication-symptom-based and multi-indicator methods, termed "phase II" methods, have been gradually adopted to assess the eutrophication status in some coastal waters in China and have achieved success. The cumulative quantile is typically selected to determine the characteristic value of an indicator in "phase II" methods. The influence of small-scale damaged water bodies on eutrophication assessment may be exaggerated, which often leads to the overassessment of the eutrophication status. In this study, the area ratio method was integrated into the assessment of the estuarine trophic status (ASSETS) method in order to assess the eutrophication status of Xiamen Bay in 2016. The results indicated that, in 2016, the eutrophication status of Xiamen Bay coastal waters was moderate and exhibited spatiotemporal variation. The area ratio method can effectively reduce the effect of small-scale coastal waters with extremely high eutrophication on the overassessment of eutrophication at the broader scale, allowing the eutrophication status to be better reflected, even with limited observation data. The centralized distribution of pollution sources and poor hydrodynamic conditions are the main reasons for the aforementioned phenomenon. Controlling the pollution discharge from the Jiulong River in flood seasons is key to reducing eutrophication in Xiamen coastal waters.

Plant growth-promoting rhizobacteria (PGPR) are important members of soil microbial communities. In this study, the effects of several PGPR on the growth of Carya illinoinensis plants, the microbial community composition and soil nutrients were investigated by inoculation tests to identify excellent PGPR strains. The experiment showed that after PGPR application, the plant height, ground diameter, and dry weight of C. illinoinensis were significantly increased compared with those of the control group, and Bacillus velezensis YH20 had the most significant effect in promoting growth (p < 0.05). In addition, all the PGPRs used for inoculation promoted plant root growth, and the Brevibacillus reuszeri MPT17 strain had the most significant promoting effect on plant root growth (p < 0.05). The application of PGPRs also affected the nutrient levels in plants and plant rhizosphere soil. For example, compared with the control, the levels of available phosphorus and potassium in rhizosphere soil and the total potassium content in plant roots were significantly increased under Br. reuszeri MPT17 treatment (p < 0.05). The experiment showed that the relative abundance of Mortierella, Dictyophora, and Bacillus in the rhizosphere soil increased significantly after the application of PGPR (p < 0.05). These genera could effectively improve the rate of soil nutrient use, antagonize plant pathogenic bacteria, and promote plant growth. This study provides basic reference data regarding the use of PGPR to improve the microecological environment and promote the growth and development of C. illinoinensis plants., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A neuromuscular junction (NMJ) (or myoneural junction) is a chemical synapse between a motor neuron (MN) and a muscle fiber. Although numerous articles have been published, no such analyses on trend or prediction of citations in NMJ were characterized using the temporal bar graph (TBG). This study is to identify the most dominant entities in the 100 top-cited articles in NMJ (T100MNJ for short) since 2001; to verify the improved TBG that is viable for trend analysis; and to investigate whether medical subject headings (MeSH terms) can be used to predict article citations., Methods: We downloaded T100MNJ from the PubMed database by searching the string ("NMJ" [MeSH Major Topic] AND ("2001" [Date - Modification]: "2021" [Date - Modification])) and matching citations to each article. Cluster analysis of citations was performed to select the most cited entities (e.g., authors, research institutes, affiliated countries, journals, and MeSH terms) in T100MNJ using social network analysis. The trend analysis was displayed using TBG with two major features of burst spot and trend development. Next, we examined the MeSH prediction effect on article citations using its correlation coefficients (CC) when the mean citations in MeSH terms were collected in 100 top-cited articles related to NMJ (T100NMJs)., Results: The most dominant entities (i.e., country, journal, MesH term, and article in T100NMJ) in citations were the US (with impact factor [IF] = 142.2 = 10237/72), neuron (with IF = 151.3 = 3630/24), metabolism (with IF = 133.02), and article authored by Wagh et al from Germany in 2006 (with 342 citing articles). The improved TBG was demonstrated to highlight the citation evolution using burst spots, trend development, and line-chart plots. MeSH terms were evident in the prediction power on the number of article citations (CC = 0.40, t = 4.34)., Conclusion: Two major breakthroughs were made by developing the improved TBG applied to bibliographical studies and the prediction of article citations using the impact factor of MeSH terms in T100NMJ. These visualizations of improved TBG and scatter plots in trend, and prediction analyses are recommended for future academic pursuits and applications in other disciplines., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The number of patients with diabetic neuropathic pain (DNP) continues to increase, but available treatments are limited. This study aimed to examine the influence of reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NOD-like receptor protein 3 (NLRP3)- N -methyl-D-aspartic acid receptor 2B (NR2B) pathway on type 2 DNP., Methods: Male Sprague-Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks. Then, rats were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg) to induce type 2 diabetes mellitus in rats. Diabetic rats with <85% of their basic levels in mechanical withdrawal threshold and thermal withdrawal latency were classified as DNP rats on day 14 after STZ injection. DNP rats were treated with ROS scavenger N-tert-Butyl-α-phenylnitrone (PBN, 100 mg·kg -1 ·d -1 ) or TXNIP small interfering ribonucleic acid (10 μg/d) once daily for 14 days. The level of ROS, protein levels of NLRP3, TXNIP, cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β (IL-1β), NR2B phosphorylation at Tyr1472 (p-NR2B), total NR2B (t-NR2B), and distribution of NLRP3 in the spinal cord were examined. In vitro experiments, BV2 cells and PC12 cells were individually cultured and cocultured in a high-glucose environment (35 mmol/L D-glucose). The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, and IL-1β in BV2 cells, and p-NR2B, t-NR2B in PC12 cells were detected. The level of ROS was detected by the flow cytometry approach. The protein levels were detected by the Western blot technique. The location of NLRP3 was observed by immunofluorescent staining. The interaction between TXNIP and NLRP3 was detected by coimmunoprecipitation assay., Results: The level of spinal ROS increased in DNP rats. The mechanical allodynia and thermal hyperalgesia of DNP rats were alleviated after systemic administration of PBN. This administration decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B and the coupling of TXNIP to NLRP3 in spinal cords of DNP rats. Furthermore, knockdown of spinal TXNIP alleviated nociceptive hypersensitivity and decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B in DNP rats. The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, IL-1β, the coupling of TXNIP to NLRP3, and the IL-1β secretion increased in BV2 cells, and the protein expression of p-NR2B increased in cocultured PC12 cells in a high-glucose environment. All of these in vitro effects were significantly blocked after treatment of PBN., Conclusions: Our findings suggest that spinal ROS can contribute to type 2 DNP through TXNIP-NLRP3-NR2B pathway., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Papilio machaon was assigned as the type species for all butterflies by Linnaeus and P. bianor is a congener but exhibits a great difference in morphology (especially larva and adult color pattern) and larval host plants from P. machaon. Thus, they are the ideal models to investigate genetic mechanisms underlying morphology and plasticity between congeners. The reference genomes of both species were dissected in our previous studies, but little is known about their regulatory genome and the epigenetic regulation of gene expression throughout developmental stages. Here, we profiled the chromatin accessibility and gene expression of three developmental stages (the 4th instar larva [L4], the 5th instar larva [L5], and pupa [P]) using transposase accessible chromatin sequencing (ATAC-seq) and RNA-seq. Results showed that many accessible chromatin peaks were identified at three developmental stages (peak number, P. machaon: 44,977 [L4], 36,919 [L5], 47,147 [P]; P. bianor: 20,341 [L4], 44,668 [L5], 62,249 [P]). Moreover, the number of differentially accessible peaks and differentially expressed genes between larval stages of each butterfly species are significantly fewer than that between larval and pupal stages, suggesting a higher similarity within larvae and a significant difference between larvae and pupae. This study added the annotated information of chromatin accessibility genome-wide of the two papilionid species and will promote the investigation of gene regulation in butterfly evolution., (© 2022 Wiley Periodicals LLC.)

Background: This research aims explored the sleep disorder (SD) role in major depressive disorder (MDD), and the SD influencing their cognition., Methods: 372 MDD patients and 457 healthy controls (HCs) were enrolled., Results: Patients increased a 38.88 times SD risk compared with HCs. In patients, visuospatial/constructional score was lower in SD than non-SD, and PSQI score was negatively associated with visuospatial/constructional score of SD. In SD and non-SD, RBANS scores were lower in MDD than HCs, excepted for visuospatial/constructional in non-SD., Conclusion: The SD as a MDD risk factor, has more serious visuospatial/constructional impairment alleviated via improving sleep/depression in patients., Competing Interests: Conflicts of Interest The authors reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI)., Methods: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded., Results: Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups., Conclusion: The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Sour bamboo shoot is a traditional Chinese fermented vegetable food. The traditional pickling method of sour bamboo shoots has the disadvantages of being time-consuming, inhomogeneous, and difficult to control. Pulsed vacuum pressure pickling (PVPP) technology uses pulsed vacuum pressure to enhance the pickling efficiency significantly. To demonstrate the effects of salt content and PVPP technical parameters on the fermentation of bamboo shoots, the sample salinity, pH value, color, crunchiness and chewiness, nitrite content, and lactic acid bacteria content during the pickling process were investigated. The salt content inside the bamboo shoots gradually increased to the equilibrium point during the pickling process. The pickling efficiency of bamboo shoots under PVPP technology increased by 34.1% compared to the traditional control groups. Meanwhile, the uniform salt distribution under PVPP technology also obtained better performance in comparison with the traditional groups. The pH value declined slowly from 5.96 to 3.70 with the extension of pickling time and sour flavor accumulated progressively. No significant differences were found in the color values ( L * , a * , and b * ) and the crunchiness of the bamboo shoot under different salt solution concentrations, vacuum pressure, and pulsation frequency ratio conditions. Colony-forming unit of lactic acid bacteria (CFU of LAB) decreased, to begin with, and then increased until the 6th day, followed by a declining trend in volatility. The nitrate content of bamboo shoots samples under PVPP treatments did not exceed the safety standard (<20 mg/kg) during the whole fermentation process, which proves the safety of PVPP technology. In conclusion, PVPP technology can safely replace the traditional method with better quality performance. The optimal PVPP processing conditions (vacuum pressure 60 kPa, 10 min vacuum pressure time vs. 4 min atmospheric pressure time, salt solution concentration 6%) have been recommended for pickling bamboo shoots with high product quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Zhang, Li, Li, Xu, Liu, Yin, Liu, Zhao, Gou, Li and Qin.)