Self-assembly of nanocrystal checkerboard patterns via non-specific interactions.

Checkerboard lattices-where the resulting structure is open, porous, and highly symmetric-are difficult to create by self-assembly. Synthetic systems that adopt such structures typically rely on shape complementarity and site-specific chemical interactions that are only available to biomolecular systems (e.g., protein, DNA). Here we show the assembly of checkerboard lattices from colloidal nanocrystals that harness the effects of multiple, coupled physical forces at disparate length scales (interfacial, interparticle, and intermolecular) and that do not rely on chemical binding. Colloidal Ag nanocubes were bi-functionalized with mixtures of hydrophilic and hydrophobic surface ligands and subsequently assembled at an air-water interface. Using feedback between molecular dynamics simulations and interfacial assembly experiments, we achieve a periodic checkerboard mesostructure that represents a tiny fraction of the phase space associated with the polymer-grafted nanocrystals used in these experiments. In a broader context, this work expands our knowledge of non-specific nanocrystal interactions and presents a computation-guided strategy for designing self-assembling materials.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

LINC00173 silence and estrone supply suppress ER+ breast cancer by estrogen receptor α degradation and LITAF activation.

Persistent activation of estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in driving the progression of estrogen receptor positive (ER+) breast cancer (BC). In the current study, LINC00173, a long non-coding RNA, was found to bind both ERα and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFα) factor (LITAF), then cooperatively to inhibit ERα protein degradation by impeding the nuclear export of ERα. Concurrently, LITAF was found to attenuate TNFα transcription after binding to LINC00173, and this attenuating transcriptional effect was quite significant under lipopolysaccharide stimulation. Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF-transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression.

[Rapid determination of 15 N-nitrosamines in air-dried yak meat using one-step QuEChERS-gas chromatography-triple quadrupole mass spectrometry].

A method based on gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) coupled with one-step QuEChERS technique was developed for the simultaneous determination of 15 N-nitrosamines in air-dried yak meat. The hydration volume, extraction solvent, extracting salt, and cleaning material were optimized according to the characteristics of the N-nitrosamines and sample matrix. The optimized conditions were as follows: 10 mL of purified water for sample hydration, acetonitrile as the extraction solvent for the sample after hydration, 4.0 g of anhydrous MgSO4 and 1.0 g of NaCl as extracting salts, 500 mg of MgSO4+25 mg of C18+50 mg of PSA as cleaning materials. Favorable recoveries of the 15 N-nitrosamines were obtained when the extraction solution was incompletely dried. Thus, the final extract was dried to below 0.5 mL under a mild nitrogen stream and then redissolved to 0.5 mL with acetonitrile. After filtration, 200 µL of the sample was transferred to an autosampler vial for GC-MS/MS analysis. The 15 N-nitrosamines were determined using GC-MS/MS on a DB-HeavyWAX column (30 m×0.25 mm×0.25 µm) with an electron impact ion source in multiple-reaction monitoring (MRM) mode, and quantified using an external standard method. Under the optimized experimental conditions, the results showed that the calibration curves exhibited good linearities for the 15 N-nitrosamines, with correlation coefficients (r2) greater than 0.9990. The limits of detection (LODs) and the limits of quantification (LOQs) ranged from 0.05 to 0.20 µg/kg and from 0.10 to 0.50 µg/kg, respectively. At spiked levels of 1LOQ, 2LOQ, and 10LOQ, the average recoveries were 79.4%-102.1%, 80.6%-109.5%, and 83.0%-110.6%, respectively, and the relative standard deviations were in the range of 0.8%-16.0%. The low matrix effects of the 15 N-nitrosamines indicated the high sensitivity of the proposed method. The method was applied to detect representative commercial air-dried yak meat samples obtained using different processing techniques. Seven N-nitrosamines, including N-nitrosodimethylamine, N-nitrosodiisobutylamine, N-nitrosodibutylamine, N-methyl-N-phenylnitrous amide, N-ethyl-N-nitrosoaniline, N-nitrosopyrrolidine, and N-nitrosodiphenylamine were detected in all samples. The average contents of the seven N-nitrosamines was 0.08-20.18 µg/kg. The detection rates and average contents of the N-nitrosamines in cooked air-dried yak meat samples were higher than those in traditional raw air-dried yak meat samples. Compared with the manual QuEChERS method, the one-step QuEChERS method developed integrated the extraction and clean-up procedures into one single run, and the detection efficiency was considerably improved. The developed method is simple, rapid, highly sensitive, and insusceptible to human errors. Thus, it is useful for the determination of N-nitrosamines in air-dried yak meat and can be extended to the qualitative and quantitative analysis of N-nitrosamines in other meat products. It also provides method support and a data reference for the general determination of N-nitrosamines, which is of great significance for food safety.

Low-index mesoscopic surface reconstructions of Au surfaces using Bayesian force fields.

Metal surfaces have long been known to reconstruct, significantly influencing their structural and catalytic properties. Many key mechanistic aspects of these subtle transformations remain poorly understood due to limitations of previous simulation approaches. Using active learning of Bayesian machine-learned force fields trained from ab initio calculations, we enable large-scale molecular dynamics simulations to describe the thermodynamics and time evolution of the low-index mesoscopic surface reconstructions of Au (e.g., the Au(111)-'Herringbone,' Au(110)-(1 × 2)-'Missing-Row,' and Au(100)-'Quasi-Hexagonal' reconstructions). This capability yields direct atomistic understanding of the dynamic emergence of these surface states from their initial facets, providing previously inaccessible information such as nucleation kinetics and a complete mechanistic interpretation of reconstruction under the effects of strain and local deviations from the original stoichiometry. We successfully reproduce previous experimental observations of reconstructions on pristine surfaces and provide quantitative predictions of the emergence of spinodal decomposition and localized reconstruction in response to strain at non-ideal stoichiometries. A unified mechanistic explanation is presented of the kinetic and thermodynamic factors driving surface reconstruction. Furthermore, we study surface reconstructions on Au nanoparticles, where characteristic (111) and (100) reconstructions spontaneously appear on a variety of high-symmetry particle morphologies.

Cervical septum incision adversely impacts clinical outcomes in women with complete uterine septum and duplicated cervix.

STUDY OBJECTIVE: To investigate the reproductive outcomes of women with complete septate uterus and duplicated cervix who either did or did not receive cervical septum incision during hysteroscopic transcervical incision of the uterine septum. DESIGN: Retrospective study approved by the Hospital Ethics Committee. SETTING: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PATIENTS: Women with complete septate uterus and duplicated cervix who underwent hysteroscopic transcervical incision of the uterine septum in Obstetrics and Gynecology Hospital of Fudan University between January 2008 and December 2020 (n=105). INTERVENTIONS: Hysteroscopic incision of the septum. MEASUREMENTS AND MAIN RESULTS: Included patients were grouped according to whether or not cervical septum incision was performed. Reproductive outcomes including gravidity, abortion rate, preterm birth rate, full-term birth rate, premature rupture of membranes (PROM), and cervical incompetence were assessed. In no incision group, the abortion rate (7.4%) was significantly lower than that of incision group (27.6%, p=0.01); the preterm birth rate (4.6%) was significantly lower than that of incision group (36.8%); and the full-term birth rate (95.5%) exceeded that of incision group (63.2%, p<0.01). Incidence of PROM and cervical incompetence during pregnancy was higher in incision group (15.8% and 10.5%, p<0.01 and p=0.03). CONCLUSION: Significantly improved reproductive outcomes were observed among patients with complete septate uterus and duplicated cervix whose cervical septum was preserved during the hysteroscopic transcervical incision of the uterine septum procedure.

Ultrashort-Peptide-Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells.

Despite the array of mammalian transgene switches available for regulating therapeutic protein expression in response to small molecules or physical stimuli, issues remain, including cytotoxicity of chemical inducers and limited biocompatibility of physical cues. This study introduces gene switches driven by short peptides comprising eight or fewer amino acid residues. Utilizing a competence regulator (ComR) and sigma factor X-inducing peptide (XIP) from Streptococcus vestibularis as the receptor and inducer, respectively, this study develops two strategies for a peptide-activated transgene control system. The first strategy involves fusing ComR with a transactivation domain and utilizes ComR-dependent synthetic promoters to drive expression of the gene-of-interest, activated by XIP, thereby confirming its membrane penetrability and intracellular functionality. The second strategy features an orthogonal synthetic receptor exposing ComR extracellularly (ComREXTRA), greatly increasing sensitivity with exceptional responsiveness to short peptides. In a proof-of-concept study, peptides are administered to type-1 diabetic mice with microencapsulated engineered human cells expressing ComREXTRA for control of insulin expression, restoring normoglycemia. It is envisioned that this system will encourage the development of short peptide drugs and promote the introduction of non-toxic, orthogonal, and highly biocompatible personalized biopharmaceuticals for gene- and cell-based therapies.

Contrast-enhanced Imaging in Peripheral Pulmonary Lesions: The Role in US-guided Biopsies.

Purpose To compare the tissue adequacy and diagnostic accuracy of US-guided biopsies of peripheral pulmonary lesions (PPLs) with and without contrast agents. Materials and Methods A retrospective study was conducted at four medical centers in patients with PPLs who underwent US-guided percutaneous transthoracic needle biopsy (PTNB) between January 2017 and October 2022. The patients were divided into contrast-enhanced US (CEUS) and US groups based on whether prebiopsy CEUS evaluation was performed. Tissue adequacy and the diagnostic accuracy of PTNB, stratified by lesion size, were analyzed and compared between groups. A propensity score matching (PSM) analysis was conducted using the nearest-neighbor matching method. Results A total of 1027 lesions were analyzed, with 634 patients (mean age, 59.4 years ± 13.0 [SD]; 413 male) in the US group and 393 patients (mean age, 61.2 years ± 12.5; 270 male) in the CEUS group. The CEUS group produced more acceptable samples than the US group (98.2% vs 95.7%; P = .03) and achieved higher diagnostic accuracy (96.9% vs 94.2%; P = .04), with no evidence of a difference in sensitivity (96.7% vs 94.0%; P = .06). PSM and stratified analyses (n = 358 per group) indicated higher tissue adequacy (99.0% vs 95.7%; P = .04) and diagnostic accuracy (98.5% vs 92.9%; P = .006) in the CEUS group compared with the US group for 2-7-cm PPLs but not for lesions larger than 7 cm. Conclusion PTNB with prebiopsy CEUS evaluation demonstrated significantly better tissue adequacy and diagnostic accuracy compared with US guidance alone for PPLs ranging from 2 to 7 cm, with similar biopsy performance achieved between groups for lesions larger than 7 cm. Keywords: Contrast Material, Thoracic Diseases, Ultrasonography, Image-Guided Biopsy © RSNA, 2024.

Multidimensional Electrochemistry Decodes the Operando Mechanism of Hydrogen Oxidation.

Being an efficient approach to the utilization of hydrogen energy, the hydrogen oxidation reaction (HOR) is of particular significance in the current carbon-neutrality time. Yet the mechanistic picture of the HOR is still blurred, mostly because the elemental steps of this reaction are rapid and highly entangled, especially when deviating from the thermodynamic equilibrium state. Here we report a strategy for decoding the HOR mechanism under operando conditions. In addition to the wide-potential-range I-V curves obtained using gas diffusion electrodes, we have applied the AC impedance spectroscopy to provide independent and complementary kinetic information. Combining multidimensional data sources has enabled us to fit, in mathematical rigor, the core kinetic parameter set in a 5-D data space. The reaction rate of the three elemental steps (Tafel, Heyrovsky, and Volmer reactions), as a function of the overpotential, can thus be distilled individually. Such an undocumented kinetic picture unravels, in detail, how the HOR is controlled by the elemental steps on polarization. For instance, at low polarization region, the Heyrovsky reaction is relatively slow and can be ignored; but at high polarization region, the Heyrovsky reaction will surpass the Tafel reaction. Additionally, the Volmer reaction has been the fastest within overpotentials of interest. Our findings not only offer a better understanding of the HOR mechanism, but also lay the foundation for the development of improved hydrogen energy utilization systems.

Induced Aggregation, Solvent Regulation, and Supracluster Assembly of Aluminum Oxo Clusters.

ConspectusRecent years have witnessed the development of cluster materials as they are atomically precise molecules with uniform size and solution-processability, which are unattainable with traditional nanoparticles or framework materials. The motivation for studying Al(III) chemistry is not only to understand the aggregation process of aluminum in the environment but also to develop novel low-cost materials given its natural abundance. However, the Al-related clusters are underdeveloped compared to the coinage metals, lanthanides, and transition metals. The challenge in isolating crystalline compounds is the lack of an effective method to realize the controllable hydrolysis of Al(III) ions. Compared with the traditional hydrolysis of inorganic Al(III) salts in highly alkaline solutions and hydrolysis of aluminum trialkyl compounds conducted carefully in an inert operating environment, we herein developed an effective way to control the hydrolysis of aluminum isopropanol through an alcoxalation reaction. By solvothermal/low melting point solid melting synthesis and using "ligand aggregation, solvent regulation, and supracluster assembly" strategies, our laboratory has established an organic-inorganic hybrid system of aluminum oxo clusters (AlOCs). The employment of organic ligands promotes the aggregation and slows the hydrolysis of Al(III) ions, which in turn improves the crystallization process. The regulation of the structure types can be achieved through the selection of ligands and the supporting solvents. Compared with the traditional condensed polyoxoaluminates, we successfully isolated a broad range of porous AlOCs, including aluminum molecular rings and Archimedes aluminum oxo cages. By studying ring expansion, structural transformation, and intermolecular supramolecular assembly, we demonstrate unique and unprecedented structural controllability and assembly behavior in cluster science. The advancement of this universal synthetic method is to realize materials customization through modularly oriented supracluster assembly. In this Account, we will provide a clear-cut definition and terminology of "ligand aggregation, solvent regulation, and supracluster assembly". Then we will discuss the discovery in this area by using a strategy, such as aluminum molecular ring, ring size expansion, ring supracluster assembly, etc. Furthermore, given the internal and external pore structures, as well as the solubility and modifiability of the AlOCs, we will demonstrate their potential applications in both the solid and liquid phases, such as iodine capture, the optical limiting responses, and dopant in polymer dielectrics. The strategy herein can be applied to extensive cluster science and promote the research of main group element chemistry. The new synthetic method, fascinating clusters, and unprecedented assembly behaviors we have discovered will advance Al(III) chemistry and will also lay the foundation for functional applications.

Comprehensive untargeted lipidomics study of black morel (Morchella sextelata) at different growth stages.

The black morel (Morchella sextelata) is a valuable edible and medicinal mushroom appreciated worldwide. Here, lipidomic profiles and lipid dynamic changes during the growth of M. sexletata were analyzed using ultra-performance liquid chromatography coupled with mass spectrometry. 203 lipid molecules, including four categories and fourteen subclasses, were identified in mature fruiting bodies, with triacylglycerol being the most abundant (37.00 %). Fatty acid composition analysis revealed that linoleic acid was the major fatty acid among the free fatty acids, glycerolipids and glycerophospholipids. The relative concentration of lipids in M. sextelata changed significantly during its growth, from which 12 and 29 differential lipid molecules were screened out, respectively. Pathway analysis based on these differential lipids showed that glycerophospholipid metabolism was the major pathway involved in the growth of M. sextelata. Our study provides a comprehensive understanding of the lipids in M. sextelata and will facilitate the development and utilization of M. sextelata.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

Alterations in the fecal microbiota of methamphetamine users with bad sleep quality during abstinence.

BACKGROUND: Methamphetamine (MA) abuse has resulted in a plethora of social issues. Sleep disturbance is a prominent issue about MA addiction, which serve as a risk factor for relapse, and the gut microbiota could play an important role in the pathophysiological mechanisms of sleep disturbances. Therefore, improving sleep quality can be beneficial for treating methamphetamine addiction, and interventions addressing the gut microbiota may represent a promising approach. METHOD: We recruited 70 MA users to investigate the associations between sleep quality and fecal microbiota by the Pittsburgh Sleep Quality Index (PSQI), which was divided into MA-GS (PSQI score < 7, MA users with good sleep quality, n = 49) and MA-BS group (PSQI score ≥ 7, MA users with bad sleep quality, n = 21). In addition, we compared the gut microbiota between the MA-GS and healthy control (HC, n = 38) groups. 16S rRNA sequencing was applied to identify the gut bacteria. RESULT: The study revealed that the relative abundances of the Thermoanaerobacterales at the order level differed between the MA-GS and MA-BS groups. Additionally, a positive correlation was found between the relative abundance of the genus Sutterella and daytime dysfunction. Furthermore, comparisons between MA users and HCs revealed differences in beta diversity and relative abundances of various bacterial taxa. CONCLUSION: In conclusion, the study investigated alterations in the gut microbiota among MA users. Furthermore, we demonstrated that the genus Sutterella changes may be associated with daytime dysfunction, suggesting that the genus Sutterella may be a biomarker for bad sleep quality in MA users.

Discrepancy between arterial oxygen saturation and pulse oximetry measurement in a Chinese pediatric patient cohort.

Background: Increasing evidence suggest a racial bias in pulse oximetry measurement, but this was under investigated in Asian pediatric populations. Methods: Via the Pediatric Intensive Care database, this retrospective study included pediatric patient records of arterial oxygen saturation (SaO2) and oxygen saturation on pulse oximetry (SpO2) measured within 10 min. Discrepancy was examined, and potential predictors of occult hypoxemia (defined as SaO2 <88% with the paired SpO2 ≥92%) as well as its association with outcomes were explored by logistic regression. Results: A total of 390 patients were included with 454 pairs of SaO2-SpO2 readings. The study population consisted of Han Chinese (99.0%) and 43.6% were female. Occult hypoxemia was observed in 20.0% of the patients, with a mean SaO2 of 71.4 ± 15.8%. Potential predictors of occult hypoxemia included female, being first admitted to cardiac ICU, congenital heart disease, increased heart rate, while patients with prior surgery records were less likely to experience occult hypoxemia. Patients with occult hypoxemia had numerically higher in-ICU mortality (16.7% versus 10.9%) and in-hospital mortality (17.9% versus 10.9%), but the associations were not statistically significant. Conclusions: There was a substantial proportion of hypoxemia that was not detected by pulse oximetry in the Chinese pediatric patients, which might be predicted by several characteristics and seemed to associate with mortality.

Laboratory evidence of Weibel magnetogenesis driven by temperature gradient using three-dimensional synchronous proton radiography.

The origin of the cosmic magnetic field remains an unsolved mystery, relying not only on specific dynamo processes but also on the seed field to be amplified. Recently, the diffuse radio emission and Faraday rotation observations reveal that there has been a microgauss-level magnetic field in intracluster medium in the early universe, which places strong constraints on the strength of the initial field and implies the underlying kinetic effects; the commonly believed Biermann battery can only provide extremely weak seed of 10-21 G. Here, we present evidence for the spontaneous Weibel-type magnetogenesis in laser-produced weakly collisional plasma with the three-dimensional synchronous proton radiography, where the distribution anisotropy directly arises from the temperature gradient, even without the commonly considered interpenetrating plasmas or shear flows. This field can achieve sufficient strength and is sensitive to Coulomb collision. Our results demonstrate the importance of kinetics in magnetogenesis in weakly collisional astrophysical scenarios.

Application of sticky bone combined with concentrated growth factor (CGF) for horizontal alveolar ridge augmentation of anterior teeth: a randomized controlled clinical study.

OBJECTIVE: This study was designed to estimate the effect of sticky bone combined with concentrated growth factor (CGF) on anterior alveolar horizontal augmentation during implantation. METHODS: Twenty-eight patients were randomly assigned to either the test group (Group 1, n = 14) or the control group (Group 2, n = 14). Patients in Group 1 and Group 2 underwent GBR using sticky bone combined with CGF and bone powders mixed with saline, respectively. On postoperative Day 7, the patients completed the visual analogue scale (VAS). Three-dimensional models of maxillary alveolar bone were reconstructed from CBCT data at different periods, and the bone volume conversion rate was calculated with the assistance of a measurement marker guide. Labial bone thickness before and after trauma closure and bone density at six months postoperatively were also measured. RESULTS: The mean bone volume conversion rate for Group 1 (72.09 ± 12.18%) was greater than that for Group 2 (57.47 ± 9.62%, P = 0.002). The VAS score was lower for Group 1 than for Group 2 (P = 0.032). At six months postoperatively, greater bone density was found in patients in Group 1 than in those in Group 2, although the difference was not statistically significant (P > 0.05). The change in the thickness of the labial bone graft material in Group 1 was smaller than that in Group 2 (P = 0.025). CONCLUSION: Sticky bone combined with CGF was able to achieve better bone augmentation than conventional GBR. With excellent mechanical properties and the capacity to release growth factors, sticky bone is an ideal material for bone grafting. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry on 10/04/2022 (Identification number: ChiCTR2200058500).

[Extracorporeal Membrane Oxygenation Combined With Interventional Thrombectomy for Treating High-Risk Pulmonary Embolism Caused by Protein C Deficiency:Report of One Case].

Hereditary protein C deficiency is a chromosomal genetic disease caused by mutations in the protein C gene,which can lead to venous thrombosis and is mostly related to mutations in exons 4-9 and intron 8.Fatal pulmonary embolism caused by mutations in the protein C gene is rare,and the treatment faces great challenges.This article reports a case of fatal pulmonary embolism caused by a frameshift mutation in exon 8 of the protein C gene and summarizes the treatment experience of combining extracorporeal membrane oxygenation (for respiratory and circulatory support) with interventional thrombectomy,providing a basis for the diagnosis and treatment of this disease.

Gut-lung axis and asthma: A historical review on mechanism and future perspective.

BACKGROUND: Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. CONCLUSION: The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs.

Nociceptive sensory neurons convey pain-related signals to the CNS using action potentials. Loss-of-function mutations in the voltage-gated sodium channel NaV1.7 cause insensitivity to pain (presumably by reducing nociceptor excitability) but clinical trials seeking to treat pain by inhibiting NaV1.7 pharmacologically have struggled. This may reflect the variable contribution of NaV1.7 to nociceptor excitability. Contrary to claims that NaV1.7 is necessary for nociceptors to initiate action potentials, we show that nociceptors can achieve similar excitability using different combinations of NaV1.3, NaV1.7, and NaV1.8. Selectively blocking one of those NaV subtypes reduces nociceptor excitability only if the other subtypes are weakly expressed. For example, excitability relies on NaV1.8 in acutely dissociated nociceptors but responsibility shifts to NaV1.7 and NaV1.3 by the fourth day in culture. A similar shift in NaV dependence occurs in vivo after inflammation, impacting ability of the NaV1.7-selective inhibitor PF-05089771 to reduce pain in behavioral tests. Flexible use of different NaV subtypes exemplifies degeneracy - achieving similar function using different components - and compromises reliable modulation of nociceptor excitability by subtype-selective inhibitors. Identifying the dominant NaV subtype to predict drug efficacy is not trivial. Degeneracy at the cellular level must be considered when choosing drug targets at the molecular level.

WTAP-induced N6-methyladenosine of PD-L1 blocked T-cell-mediated antitumor activity under hypoxia in colorectal cancer.

N6-Methyladenosine (m6A) is a important process regulating gene expression post-transcriptionally. Programmed death ligand 1 (PD-L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1-associated protein (WTAP) degradation caused by ubiquitin-mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD-L1 expression in a way that was m6A-dependent. m6A "reader," Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) identified methylated PD-L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T-cell proliferation and its cancer cell-killing effects were prevented by overexpression of WTAP in vitro and in vivo. Overexpression prevented T cells from proliferating and killing CRC by maintaining the expression of PD-L1. Further evidence supporting the WTAP-PD-L1 regulatory axis was found in human CRC and organoid tissues. Tumors with high WTAP levels appeared more responsive to anti-PD1 immunotherapy, when analyzing samples from patients undergoing treatment. Overall, our findings demonstrated a novel PD-L1 regulatory mechanism by WTAP-induced mRNA epigenetic regulation and the possible application of targeting WTAP as immunotherapy for tumor hypoxia.