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1.
Sci Total Environ ; 947: 174405, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960186

ABSTRACT

In this study, the chemical mechanisms of O3 and nitrate formation as well as the control strategy were investigated based on extensive observations in Tai'an city in the NCP and an observation-constrained box model. The results showed that O3 pollution was severe with the maximum hourly O3 concentration reaching 150 ppb. Higher O3 concentration was typically accompanied by higher PM2.5 concentrations, which could be ascribed to the common precursors of VOCs and NOx. The modeled averaged peak concentrations of OH, HO2, and RO2 were relatively higher compared to previous observations, indicating strong atmospheric oxidation capacity in the study area. The ROx production rate increased from 2.8 ppb h-1 to 5 ppb h-1 from the clean case to the heavily polluted case and was dominated by HONO photolysis, followed by HCHO photolysis. The contribution of radical-self combination to radical termination gradually exceeded NO2 + OH from clean to polluted cases, indicating that O3 formation shifted to a more NOx-limited regime. The O3 production rate increased from 14 ppb h-1 to 22 ppb h-1 from clean to heavily polluted cases. The relative incremental reactivity (RIR) results showed that VOCs and NOx had comparable RIR values during most days, which suggested that decreasing VOCs or NOx was both effective in alleviating O3 pollution. In addition, HCHO, with the largest RIR value, made important contribution to O3 production. The Empirical Kinetic Modeling Approach (EKMA) revealed that synergistic control of O3 and nitrate can be achieved by decreasing both NOx and VOCs emissions (e.g., alkenes) with the ratio of 3:1. This study emphasized the importance of NOx abatement for the synergistic control of O3 and nitrate pollution in the Tai'an area as the sustained emissions control has shifted the O3 and nitrate formation to a more NOx-limited regime.

2.
Front Neurol ; 15: 1376019, 2024.
Article in English | MEDLINE | ID: mdl-38957353

ABSTRACT

Introduction: Neurogenic hypertension (HTN) is a type of HTN characterized by increased activity of the sympathetic nervous system. Vascular compression is one of the pathogenic mechanisms of neurogenic HTN. Despite Jannetta's solid anatomical and physiological arguments in favor of neurogenic HTN in the 1970's, the treatment for essential HTN by microvascular decompression (MVD) still lacks established selection criteria. Therefore, the subjects selected for our center were limited to patients with primary trigeminal neuralgia (TN) and primary hemifacial spasm (HFS) of the vertebral/basilar artery (VA/BA) responsible vessel type coexisting with neurogenic HTN who underwent MVD of the brainstem to further explore possible indications for MVD in the treatment of neurogenic HTN. Methods: A retrospective analysis of 63 patients who were diagnosed with neurogenic HTN had symptoms of HFS and TN cranial nerve disease. Patients were treated at our neurosurgery department from January 2018 to January 2023. A preoperative magnetic resonance examination of the patients revealed the presence of abnormally located vascular compression in the rostral ventrolateral medulla (RVLM) and the root entry zone (REZ) of the IX and X cranial nerves (CN IX- X). Results: There was no significant difference between the two groups in terms of gender, age, course of HFS, course of TN, course of HTN, degree of HTN, or preoperative blood pressure. Based on the postoperative blood pressure levels, nine out of 63 patients were cured (14.28%), eight cases (12.70%) showed a marked effect, 16 cases (25.40%) were effective, and 30 cases were invalid (47.62%). The overall efficacy was 52.38%. However, 39 cases of combined cranial nerve disease were on the left side of the efficacy rate (66.67%) and 24 cases of combined cranial nerve disease were on the right side of the efficacy rate (29.16%). Discussion: Over the last few decades, many scholars have made pioneering progress in the clinical retrospective study of MVD for neurogenic hypertension, and our study confirms the efficacy of MVD in treating vertebral/basilar artery-type neurogenic hypertension by relieving the vascular pressure of RVLM. In the future, with the development and deepening of pathological mechanisms and clinical observational studies, MVD may become an important treatment for neurogenic hypertension by strictly grasping the surgical indications. Conclusion: MVD is an effective treatment for neurogenic HTN. Indications may include the following: left-sided TN or HFS combined with neurogenic HTN; VA/BA compression in the left RVLM and REZ areas on MRI; and blood pressure in these patients cannot be effectively controlled by drugs.

3.
Anal Methods ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994818

ABSTRACT

Exosomal microRNAs (exomiRs) have been shown to play crucial roles as biomarkers for early detection and prognosis of cancer. However, simultaneous quantification of multiplex exomiRs is hindered by methods that require additional steps, such as labeling with fluorophores or gel visualization, which are susceptible to various factors. Herein, we developed a mass spectrometry-detectable and target-triggered method for multiplexed exomiR detection using three enzyme-based double recycling amplification in combination with well-designed molecular beacon-peptide (MBP) probes, called molecular beacon-peptide probe-based double recycling amplification (MBPDRA). MBP probes mediated the double recycling amplification reaction and were released as mass-detectable reporter peptides. In particular, the hybridization of the target microRNAs (miRNAs) with the stem-loop of the probe triggers two consecutive processes. The first cycle involved polymerase strand displacement amplification, leading to the production of complementary DNA (cycle I), and the second cycle encompassed the recycling exonuclease cleavage of the MBP probe (cycle II). Subsequently, excess probes were removed by interaction with streptavidin beads via biotin-streptavidin binding. The reporter peptides were released using trypsin and subsequently detected by mass spectrometry. Our method enables quantitative detection of multiple exomiRs with a dynamic range from 0.1 fM to 10 pM and a limit of quantification of 0.1 fM. Moreover, the proposed assay was successfully employed for quantification of three exomiRs, exmiR-21, exmiR-191, and exmiR-451a, in the sera of patients with pancreatic cancer. Based on these findings, we believe that the MBPDRA assay holds significant promise as a reliable method for quantifying multiple miRNAs in biomedical research and clinical diagnostics.

4.
Adv Sci (Weinh) ; : e2400979, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994880

ABSTRACT

Reconstructing the visible spectra of real objects is critical to the spectral camouflage from emerging spectral imaging. Electrochromic materials exhibit unique superiority for this goal due to their subtractive color-mixing model and structural diversity. Herein, a simulation model is proposed and a method is developed to fabricate electrochromic devices for dynamically reproducing the visible spectrum of the natural leaf. Over 20 kinds of pH-dependent leuco dyes have been synthesized/prepared through molecular engineering and offered available spectra/bands to reconstruct the spectrum of the natural leaf. More importantly, the spectral variance between the device and leaf is optimized from an initial 98.9 to an ideal 10.3 through the simulation model, which means, the similarity increased nearly nine-fold. As a promising spectrum reconstruction approach, it will promote the development of smart photoelectric materials in adaptive camouflage, spectral display, high-end encryption, and anti-counterfeiting.

5.
Case Rep Dermatol ; 16(1): 156-163, 2024.
Article in English | MEDLINE | ID: mdl-39015395

ABSTRACT

Introduction: Pilomatrix carcinomas (PMXCs) are uncommon, locally aggressive tumors with high recurrence rates, metastatic potential, and fewer than 130 cases reported in the literature. Typically, they present as an unassuming, firm, dermal swelling and therefore are frequently mistaken for more common, benign masses, leading to undertreatment which can cause local invasion and metastatic spread. Diagnosis relies on excision with pathologic analysis; however once diagnosed, there are no current recommendations to guide treatment or surveillance for recurrence or metastases. Case Presentation: Here, we present a case of one of these rare tumors. Our case describes a 1.5 × 2.5 cm firm, mobile mass at the supraorbital rim in an otherwise healthy, young patient. Prior to removal, we suspected a benign pathology; however, excision proved difficult and pathologic diagnosis was consistent with PMXC. Following discussion with tumor board, decision was made to perform Mohs micrographic surgery and staging via CT scans with regular follow-up and surveillance scans. Conclusion: PMXCs are exceedingly rare diagnoses and present like many benign lesions. Therefore, we elected to document this case to encourage providers to keep these biologically aggressive tumors on their list of differential diagnoses in an unsuspecting mass, as well as to provide our own recommendations for treatment and screening for recurrence and metastatic spread.

6.
Carcinogenesis ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023209

ABSTRACT

Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.

7.
Genome Biol Evol ; 16(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38946297

ABSTRACT

Schoenoplectus tabernaemontani (C. C. Gmelin) Palla is a typical macrophyte in diverse wetland ecosystems. This species holds great potential in decontamination applications and carbon sequestration. Previous studies have shown that this species may have experienced recent polyploidization. This would make S. tabernaemontani a unique model to study the processes and consequences of whole-genome duplications in the context of the well-documented holocentric chromosomes and dysploidy events in Cyperaceae. However, the inference was not completely solid because it lacked homology information that is essential to ascertain polyploidy. We present here the first chromosome-level genome assembly for S. tabernaemontani. By combining Oxford Nanopore Technologies (ONT) long reads and Illumina short reads, plus chromatin conformation via the Hi-C method, we assembled a genome spanning 507.96 Mb, with 99.43% of Hi-C data accurately mapped to the assembly. The assembly contig N50 value was 3.62 Mb. The overall BUSCO score was 94.40%. About 68.94% of the genome was comprised of repetitive elements. A total of 36,994 protein-coding genes were predicted and annotated. Long terminal repeat retrotransposons accounted for ∼26.99% of the genome, surpassing the content observed in most sequenced Cyperid genomes. Our well-supported haploid assembly comprised 21 pseudochromosomes, each harboring putative holocentric centromeres. Our findings corroborated a karyotype of 2n = 2X = 42. We also confirmed a recent whole-genome duplication occurring after the divergence between Schoenoplecteae and Bolboschoeneae. Our genome assembly expands the scope of sequenced genomes within the Cyperaceae family, encompassing the fifth genus. It also provides research resources on Cyperid evolution and wetland conservation.


Subject(s)
Chromosomes, Plant , Cyperaceae , Genome, Plant , Cyperaceae/genetics , Chromosomes, Plant/genetics , Gene Duplication , Polyploidy , Evolution, Molecular
8.
Angew Chem Int Ed Engl ; : e202409708, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973371

ABSTRACT

Organic piezoelectric nanogenerators (PENGs) are attractive in harvesting mechanical energy for various self-powering systems. However, their practical applications are severely restricted by their low output open circuit voltage. To address this issue, herein, we prepared two two-dimensional (2D) covalent organic frameworks (COFs, CityU-13 and CityU-14), functionalized with fluorinated alkyl chains for PENGs. The piezoelectricity of both COFs was evidenced by switchable polarization, characteristic butterfly amplitude loops, phase hysteresis loops, conspicuous surface potentials and high piezoelectric coefficient value (d33). The PENGs fabricated with COFs displayed highest output open circuit voltages (60 V for CityU-13 and 50 V for CityU-14) and delivered satisfactory short circuit current with an excellent stability of over 600 seconds. The superior open circuit voltages of CityU-13 and CityU-14 rank in top 1 and 2 among all reported organic materials-based PENGs.

9.
bioRxiv ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38979164

ABSTRACT

ZYG11B is a substrate specificity factor for Cullin-RING ubiquitin ligase (CRL2) involved in many biological processes, including Gly/N-degron pathways. Yet how the binding of ZYG11B with CRL2 is coupled to substrate recognition and ubiquitination is unknown. We present the Cryo-EM structures of the CRL2-ZYG11B holoenzyme alone and in complex with a Gly/N-peptide from the inflammasome-forming pathogen sensor NLRP1. The structures indicate ZYG11B folds into a Leucine-Rich Repeat followed by two armadillo repeat domains that promote assembly with CRL2 and recognition of NLRP1 Gly/N-degron. ZYG11B promotes activation of the NLRP1 inflammasome through recognition and subsequent ubiquitination of the NLRP1 Gly/N-degron revealed by viral protease cleavage. Our structural and functional data indicate that blocking ZYG11B recognition of the NLRP1 Gly/N-degron inhibits NLRP1 inflammasome activation by a viral protease. Overall, we show how the CRL2-ZYG11B E3 ligase complex recognizes Gly/N-degron substrates, including those that are involved in viral protease-mediated activation of the NLRP1 inflammasome.

10.
J Anim Sci Biotechnol ; 15(1): 94, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38971799

ABSTRACT

BACKGROUND: C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo. This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls. Thirty finishing Angus bulls (626 ± 69 kg, 21 ± 0.5 months) were divided into 3 treatments according to the randomized block design: (1) control diet without additional fat (CON), (2) CON + 2.5% palmitic acid calcium salt (PA, 90% C16:0), and (3) CON + 2.5% mixed fatty acid calcium salt (MA, 60% C16:0 + 30% cis-9 C18:1). The experiment lasted for 104 d, after which all the bulls were slaughtered and sampled for analysis. RESULTS: MA tended to reduce 0-52 d dry matter intake compared to PA (DMI, P = 0.052). Compared with CON and MA, PA significantly increased 0-52 d average daily gain (ADG, P = 0.027). PA tended to improve the 0-52 d feed conversion rate compared with CON (FCR, P = 0.088). Both PA and MA had no significant effect on 52-104 days of DMI, ADG and FCR (P > 0.05). PA tended to improve plasma triglycerides compared with MA (P = 0.077), significantly increased plasma cholesterol (P = 0.002) and tended to improve subcutaneous adipose weight (P = 0.066) when compared with CON and MA. Both PA and MA increased visceral adipose weight compared with CON (P = 0.021). Only PA increased the colonization of Rikenellaceae, Ruminococcus and Proteobacteria in the cecum, and MA increased Akkermansia abundance (P < 0.05). Compared with CON, both PA and MA down-regulated the mRNA expression of Claudin-1 in the jejunum (P < 0.001), increased plasma diamine oxidase (DAO, P < 0.001) and lipopolysaccharide (LPS, P = 0.045). Compared with CON and MA, PA down-regulated the ZO-1 in the jejunum (P < 0.001) and increased plasma LPS-binding protein (LBP, P < 0.001). Compared with CON, only PA down-regulated the Occludin in the jejunum (P = 0.013). Compared with CON, PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose (P < 0.001) and increased plasma IL-6 (P < 0.001). Compared with CON, only PA up-regulated the TNF-α in the visceral adipose (P = 0.01). Compared with CON and MA, PA up-regulated IL-6 in the visceral adipose (P < 0.001), increased plasma TNF-α (P < 0.001), and reduced the IgG content in plasma (P = 0.035). Compared with CON, PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle (P < 0.05), while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1. However, neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON (P > 0.05). CONCLUSIONS: MA containing 30% cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity, adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization, improving colonization of Akkermansia, reducing intestinal barrier damage, and down-regulating NF-κB activation.

11.
Nat Commun ; 15(1): 5681, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971813

ABSTRACT

Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 µs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.

12.
BMC Biol ; 22(1): 153, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982460

ABSTRACT

Pre-mRNA splicing is a significant step for post-transcriptional modifications and functions in a wide range of physiological processes in plants. Human NHP2L binds to U4 snRNA during spliceosome assembly; it is involved in RNA splicing and mediates the development of human tumors. However, no ortholog has yet been identified in plants. Therefore, we report At4g12600 encoding the ortholog NHP2L protein, and AtSNU13 associates with the component of the spliceosome complex; the atsnu13 mutant showed compromised resistance in disease resistance, indicating that AtSNU13 is a positive regulator of plant immunity. Compared to wild-type plants, the atsnu13 mutation resulted in altered splicing patterns for defense-related genes and decreased expression of defense-related genes, such as RBOHD and ALD1. Further investigation shows that AtSNU13 promotes the interaction between U4/U6.U5 tri-snRNP-specific 27 K and the motif in target mRNAs to regulate the RNA splicing. Our study highlights the role of AtSNU13 in regulating plant immunity by affecting the pre-mRNA splicing of defense-related genes.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Plant Immunity , RNA Precursors , RNA Splicing , Plant Immunity/genetics , Arabidopsis/genetics , Arabidopsis/immunology , RNA Precursors/genetics , RNA Precursors/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Spliceosomes/metabolism , Spliceosomes/genetics , Plant Diseases/genetics , Plant Diseases/immunology
13.
Front Cell Infect Microbiol ; 14: 1380708, 2024.
Article in English | MEDLINE | ID: mdl-39006745

ABSTRACT

Introduction: The escalating occurrence of infectious disease outbreaks in humans and animals necessitates innovative, effective, and integrated research to better comprehend their transmission and dynamics. Viral infection in livestock has led to profound economic losses globally. Pneumonia is the prevalent cause of death in sheep. However, very few studies exist regarding virus-related pathogens in sheep. Metagenomics sequencing technologies in livestock research hold significant potential to elucidate these contingencies and enhance our understanding. Methods: Therefore, this study aims to characterize respiratory viromes in paired nasal swabs from Inner Mongolian feedlot sheep in China using metaviromic sequencing. Through deep sequencing, de novo assembly, and similarity searches using translated protein sequences, several previously uncharacterized and known viruses were identified in this study. Results: Among these discoveries, a novel Bovine Rhinitis B Virus (BRBV) (BRBV-sheep) strain was serendipitously detected in the nasal swabs of domestic sheep (Ovis aries). To facilitate further molecular epidemiological studies, the entire genome of BRBV-sheep was also determined. Owing to the unique sequence characteristics and phylogenetic position of BRBV-sheep, genetically distinct lineages of BRBV in sheep may exist. A TaqMan-based qRT-PCR assay targeting the 3D polymerase gene was developed and used to screen 592 clinical sheep specimens. The results showed that 44.59% of the samples (264/592) were positive. These findings suggest that BRBV sheep are widespread among Inner Mongolian herds. Conclusion: This discovery marks the initial identification of BRBV in sheep within Inner Mongolia, China. These findings contribute to our understanding of the epidemiology and genetic evolution of BRBV. Recognizing the presence of BRBV in sheep informs strategies for disease management and surveillance and the potential development of targeted interventions to control its spread.


Subject(s)
Phylogeny , Sheep Diseases , Animals , China/epidemiology , Sheep , Sheep Diseases/virology , Sheep Diseases/epidemiology , Sheep, Domestic , Nose/virology , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing , Metagenomics/methods
14.
Circulation ; 150(3): 215-229, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39008559

ABSTRACT

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.


Subject(s)
Acculturation , Cardiovascular Diseases , Diet , Gastrointestinal Microbiome , Hispanic or Latino , Humans , Male , Female , Cardiovascular Diseases/blood , Cardiovascular Diseases/ethnology , Middle Aged , United States/epidemiology , Adult , Diet/adverse effects , Risk Factors , Incidence
15.
EMBO J ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009676

ABSTRACT

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

16.
Dig Dis Sci ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009916

ABSTRACT

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

17.
Sensors (Basel) ; 24(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39000983

ABSTRACT

The thermal properties of bipolar plates, being key elements of polymer electrolyte membrane fuel cells, significantly affect their heat conduction and management. This study employed an innovative approach known as a heat flow loop integral method to experimentally assess the in-plane thermal conductivity of graphite bipolar plates, addressing the constraints of traditional methods that have strict demands for thermal stimulation, boundary or initial conditions, and sample size. This method employs infrared thermal imaging to gather information from the surface temperature field of the sample, which is induced by laser stimulation. An enclosed test loop on the infrared image of the sample's surface, situated between the heat source and the sample's boundary, is utilized to calculate the in-plane heat flow density by integrating the temperature at the sampling locations on the loop and the in-plane thermal conductivity can be determined based on Fourier's law of heat conduction. The numerical simulation analysis of the graphite models and the experimental tests with aluminum have confirmed the precision and practicality of this method. The results of 1060 aluminum and 6061 aluminum samples, each 1 and 2 mm in thickness, show a deviation between the reference and actual measurements of the in-plane thermal conductivity within 4.3% and repeatability within 2.7%. Using the loop integral method, the in-plane thermal conductivities of three graphite bipolar plates with thicknesses of 0.5 mm, 1 mm, and 1.5 mm were tested, resulting in 311.98 W(m·K)-1, 314.41 W(m·K)-1, and 323.48 W(m·K)-1, with repeatabilities of 0.9%, 3.0%, and 2.0%, respectively. A comparison with the reference value from the simulation model for graphite bipolar plates with the same thickness showed a deviation of 4.7%. The test results for three different thicknesses of graphite bipolar plates show a repeatability of 2.6%, indicating the high consistency and reliability of this measurement method. Consequently, as a supplement to existing technology, this method can achieve a rapid and nondestructive measurement of materials such as graphite bipolar plates' in-plane thermal conductivity.

18.
Crit Rev Biotechnol ; : 1-20, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004513

ABSTRACT

Microbial-based bio-refining promotes the development of a biotechnology revolution to encounter and tackle the enormous challenges in petroleum-based chemical production by biomanufacturing, biocomputing, and biosensing. Nevertheless, microbial metabolic homeostasis is often incompatible with the efficient synthesis of bioproducts mainly due to: inefficient metabolic flow, robust central metabolism, sophisticated metabolic network, and inevitable environmental perturbation. Therefore, this review systematically summarizes how to optimize microbial metabolic homeostasis by strengthening metabolic flux for improving biotransformation turnover, redirecting metabolic direction for rewiring bypass pathway, and reprogramming metabolic network for boosting substrate utilization. Future directions are also proposed for providing constructive guidance on the development of industrial biotechnology.

19.
Shanghai Kou Qiang Yi Xue ; 33(2): 164-169, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-39005093

ABSTRACT

PURPOSE: The characteristics of saliva and intestinal microbial community in children with high caries and no caries were analyzed by 16S rDNA high-throughput sequencing. METHODS: Among 431 children aged 3-5 years old in Zunyi City who were investigated previously by our team, 25 children in the high caries group and the same in the caries-free group were selected for fecal and saliva samples. 16S rDNA high-throughput sequencing was used to analyze the bacterial flora structure of the samples and identify the species with different relative abundance at the species level. SPSS 18.0 software package was used for data analysis. RESULTS: The diversity of intestinal flora in the high caries group was higher than that in the caries-free group, and the difference was statistically significant(P<0.05). The diversity of salivary flora in the high caries group was more than that in the caries-free group, with no significant difference(P>0.05). At phylum level,there was no significant difference in intestinal and salivary flora between children with high caries and children without caries. At gene level, Blautia, [Eubacterium] hallii group and [Eubacterium] eligens group in the intestine of caries-free group were significantly higher than those of high caries group(P<0.05), while Parasutterella and Christensenellaceae R-7 group were significantly lower than those of high caries group(P<0.05). At gene level, Peptostreptococcus in saliva of caries-free group was significantly higher than that in high caries group(P<0.05). Dialister, Kingella, Escherichia-Shigella and Treponema in saliva of caries-free group were significantly lower than those in high caries group(P<0.05). CONCLUSIONS: There are significant differences in species composition of intestinal flora but no in salivary flora between children with high caries and children without caries.


Subject(s)
Dental Caries , Gastrointestinal Microbiome , High-Throughput Nucleotide Sequencing , RNA, Ribosomal, 16S , Saliva , Humans , Saliva/microbiology , Dental Caries/microbiology , Child, Preschool , High-Throughput Nucleotide Sequencing/methods , RNA, Ribosomal, 16S/genetics , Gastrointestinal Microbiome/genetics , Feces/microbiology , Eubacterium/genetics , DNA, Bacterial/genetics , DNA, Ribosomal/genetics
20.
Anal Chem ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007547

ABSTRACT

Cross-linking mass spectrometry (XL-MS) is a powerful tool for elucidating protein structures and protein-protein interactions (PPIs) at the global scale. However, sensitive XL-MS analysis of mass-limited samples remains challenging, due to serious sample loss during sample preparation of the low-abundance cross-linked peptides. Herein, an optimized miniaturized filter-aided sample preparation (O-MICROFASP) method was presented for sensitive XL-MS analysis of microscale samples. By systematically investigating and optimizing crucial experimental factors, this approach dramatically improves the XL identification of low and submicrogram samples. Compared with the conventional FASP method, more than 7.4 times cross-linked peptides were identified from single-shot analysis of 1 µg DSS cross-linked HeLa cell lysates (440 vs 59). The number of cross-linked peptides identified from 0.5 µg HeLa cell lysates was increased by 58% when further reducing the surface area of the filter to 0.058 mm2 in the microreactor. To deepen the identification coverage of XL-proteome, five different types of cross-linkers were used and each µg of cross-linked HeLa cell lysates was processed by O-MICROFASP integrated with tip-based strong cation exchange (SCX) fractionation. Up to 2741 unique cross-linked peptides were identified from the 5 µg HeLa cell lysates, representing 2579 unique K-K linkages on 1092 proteins. About 96% of intraprotein cross-links were within the maximal distance restraints of 26 Å, and 75% of the identified PPIs reported by the STRING database were with high confidence (scores ≥0.9), confirming the high validity of the identified cross-links for protein structural mapping and PPI analysis. This study demonstrates that O-MICROFASP is a universal and efficient method for proteome-wide XL-MS analysis of microscale samples with high sensitivity and reliability.

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