Septo-dentate gyrus cholinergic circuits modulate function and morphogenesis of adult neural stem cells through granule cell intermediaries.

Cholinergic neurons in the basal forebrain play a crucial role in regulating adult hippocampal neurogenesis (AHN). However, the circuit and molecular mechanisms underlying cholinergic modulation of AHN, especially the initial stages of this process related to the generation of newborn progeny from quiescent radial neural stem cells (rNSCs), remain unclear. Here, we report that stimulation of the cholinergic circuits projected from the diagonal band of Broca (DB) to the dentate gyrus (DG) neurogenic niche promotes proliferation and morphological development of rNSCs, resulting in increased neural stem/progenitor pool and rNSCs with longer radial processes and larger busy heads. Interestingly, DG granule cells (GCs) are required for DB-DG cholinergic circuit-dependent modulation of proliferation and morphogenesis of rNSCs. Furthermore, single-nucleus RNA sequencing of DG reveals cell type-specific transcriptional changes in response to cholinergic circuit stimulation, with GCs (among all the DG niche cells) exhibiting the most extensive transcriptional changes. Our findings shed light on how the DB-DG cholinergic circuits orchestrate the key niche components to support neurogenic function and morphogenesis of rNSCs at the circuit and molecular levels.

The binding of PKCε and MEG2 to STAT3 regulates IL-6-mediated microglial hyperalgesia during inflammatory pain.

Studies have suggested that microglial IL-6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL-6-mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t-STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, GLUT3, and TREM2 were assessed by Western blot. IL-6 promoter activity and IL-6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL-6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL-6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL-6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.

Excessive apoptosis of Rip1-deficient T cells leads to premature aging.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.

Complete chloroplast genome structural characterization of two Aerides (Orchidaceae) species with a focus on phylogenetic position of Aerides flabellata.

BACKGROUND: The disputed phylogenetic position of Aerides flabellata Rolfe ex Downie, due to morphological overlaps with related species, was investigated based on evidence of complete chloroplast (cp) genomes. The structural characterization of complete cp genomes of A. flabellata and A. rosea Lodd. ex Lindl. & Paxton were analyzed and compared with those of six related species in "Vanda-Aerides alliance" to provide genomic information on taxonomy and phylogeny. RESULTS: The cp genomes of A. flabellata and A. rosea exhibited conserved quadripartite structures, 148,145 bp and 147,925 bp in length, with similar GC content (36.7 ~ 36.8%). Gene annotations revealed 110 single-copy genes, 18 duplicated in inverted regions, and ten with introns. Comparative analysis across related species confirmed stable sequence identity and higher variation in single-copy regions. However, there are notable differences in the IR regions between two Aerides Lour. species and the other six related species. The phylogenetic analysis based on CDS from complete cp genomes indicated that Aerides species except A. flabellata formed a monophyletic clade nested in the subtribe Aeridinae, being a sister group to Renanthera Lour., consistent with previous studies. Meanwhile, a separate clade consisted of A. flabellata and six Vanda R. Br. species was formed, as a sister taxon to Holcoglossum Schltr. CONCLUSIONS: This research was the first report on the complete cp genomes of A. flabellata. The results provided insights into understanding of plastome evolution and phylogenetic relationships of Aerides. The phylogenetic analysis based on complete cp genomes showed that A. flabellata should be placed in Vanda rather than in Aerides.

Benchmarking short and long read polishing tools for nanopore assemblies: achieving near-perfect genomes for outbreak isolates.

BACKGROUND: Oxford Nanopore provides high throughput sequencing platforms able to reconstruct complete bacterial genomes with 99.95% accuracy. However, even small levels of error can obscure the phylogenetic relationships between closely related isolates. Polishing tools have been developed to correct these errors, but it is uncertain if they obtain the accuracy needed for the high-resolution source tracking of foodborne illness outbreaks. RESULTS: We tested 132 combinations of assembly and short- and long-read polishing tools to assess their accuracy for reconstructing the genome sequences of 15 highly similar Salmonella enterica serovar Newport isolates from a 2020 onion outbreak. While long-read polishing alone improved accuracy, near perfect accuracy (99.9999% accuracy or ~ 5 nucleotide errors across the 4.8 Mbp genome, excluding low confidence regions) was only obtained by pipelines that combined both long- and short-read polishing tools. Notably, medaka was a more accurate and efficient long-read polisher than Racon. Among short-read polishers, NextPolish showed the highest accuracy, but Pilon, Polypolish, and POLCA performed similarly. Among the 5 best performing pipelines, polishing with medaka followed by NextPolish was the most common combination. Importantly, the order of polishing tools mattered i.e., using less accurate tools after more accurate ones introduced errors. Indels in homopolymers and repetitive regions, where the short reads could not be uniquely mapped, remained the most challenging errors to correct. CONCLUSIONS: Short reads are still needed to correct errors in nanopore sequenced assemblies to obtain the accuracy required for source tracking investigations. Our granular assessment of the performance of the polishing pipelines allowed us to suggest best practices for tool users and areas for improvement for tool developers.

PRMT2 silencing regulates macrophage polarization through activation of STAT1 or inhibition of STAT6.

BACKGROUND: Macrophages play significant roles in innate immune responses and are heterogeneous cells that can be polarized into M1 or M2 phenotypes. PRMT2 is one of the type I protein arginine methyltransferases involved in inflammation. However, the role of PRMT2 in M1/M2 macrophage polarization remains unclear. Our study revealed the effect and mechanism of PRMT2 in macrophage polarization. METHODS: Bone marrow-derived macrophages (BMDMs) were polarized to M1 or M2 state by LPS plus murine recombinant interferon-γ (IFN-γ) or interleukin-4 (IL-4). Quantitative polymerase chain reaction (qPCR), western blot and flow cytometry (FCM) assay were performed and analyzed markers and signaling pathways of macrophage polarization. RESULTS: We found that PRMT2 was obviously upregulated in LPS/IFN-γ-induced M1 macrophages, but it was little changed in IL-4-induced M2 macrophages. Furthermore, PRMT2 konckdown increased the expression of M1 macrophages markers through activation of STAT1 and decreased the expression of M2 macrophages markers through inhibition of STAT6. CONCLUSIONS: PRMT2 silencing modulates macrophage polarization by activating STAT1 to promote M1 and inhibiting STAT6 to attenuate the M2 state.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway.

BACKGROUND: Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages. METHODS: Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1ß, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD. RESULTS: There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1ß and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway. CONCLUSION: Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.

The Effect of Perioperative Dexamethasone on Postoperative Complications After Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. One hundred thirty-four patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference: -3.8; 95% CI: -8.4 to 0.7; P = 0.100). The incidence of major complications (Clavien-Dindo grade ≥III; 12.7% vs 16.0%, risk ratio: 0.79; 95% CI: 0.44 to 1.43; P = 0.439) and postoperative pancreatic fistula (25.4% vs 31.3%, risk ratio: 0.81; 95% CI: 0.55 to 1.19; P = 0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n = 202), the CCI score was significantly lower in the dexamethasone group (mean difference: -6.4; 95% CI: -11.2 to -1.6; P = 0.009). CONCLUSIONS: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer.

BACKGROUND: The cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer. METHODS: The single-cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty-four genes from SECRETORY_PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP-counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan-carcinoma analysis were used to examine the performance of prognostic model. RESULTS: Eighteen prognostic genes from SECRETORY_PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor-related pathways, such as PATHWAYS_IN_CANCER and B_CELL_RECEPTOR_SIGNALING_PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four-gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high- and low-RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan-carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy. CONCLUSIONS: Based on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer.

The characteristics of BCR-CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccinated volunteers.

The global COVID-19 pandemic has caused more than 1 billion infections, and numerous SARS-CoV-2 vaccines developed rapidly have been administered over 10 billion doses. The world is continuously concerned about the cytokine storms induced by the interaction between SARS-CoV-2 and host, long COVID, breakthrough infections postvaccination, and the impact of SARS-CoV-2 variants. BCR-CDR3 repertoire serves as a molecular target for monitoring the antiviral response "trace" of B cells, evaluating the effects, mechanisms, and memory abilities of individual responses to B cells, and has been successfully applied in analyzing the infection mechanisms, vaccine improvement, and neutralizing antibodies preparation of influenza virus, HIV, MERS, and Ebola virus. Based on research on BCR-CDR3 repertoire of COVID-19 patients and volunteers who received different SARS-CoV-2 vaccines in multiple laboratories worldwide, we focus on analyzing the characteristics and changes of BCR-CDR3 repertoire, such as diversity, clonality, V&J genes usage and pairing, SHM, CSR, shared CDR3 clones, as well as the summary on BCR sequences targeting virus-specific epitopes in the preparation and application research of SARS-CoV-2 potential therapeutic monoclonal antibodies. This review provides comparative data and new research schemes for studying the possible mechanisms of differences in B cell response between SARS-CoV-2 infection or vaccination, and supplies a foundation for improving vaccines after SARS-CoV-2 mutations and potential antibody therapy for infected individuals.

The effect of non-insulin-based insulin resistance indices on the prediction of recurrence in patients with atrial fibrillation undergoing radiofrequency catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

METTL3-m6A methylation inhibits the proliferation and viability of type II alveolar epithelial cells in acute lung injury by enhancing the stability and translation efficiency of Pten mRNA.

BACKGROUND: The pathogenesis of acute lung injury (ALI) involves a severe inflammatory response, leading to significant morbidity and mortality. N6-methylation of adenosine (m6A), an abundant mRNA nucleotide modification, plays a crucial role in regulating mRNA metabolism and function. However, the precise impact of m6A modifications on the progression of ALI remains elusive. METHODS: ALI models were induced by either intraperitoneal injection of lipopolysaccharide (LPS) into C57BL/6 mice or the LPS-treated alveolar type II epithelial cells (AECII) in vitro. The viability and proliferation of AECII were assessed using CCK-8 and EdU assays. The whole-body plethysmography was used to record the general respiratory functions. M6A RNA methylation level of AECII after LPS insults was detected, and then the "writer" of m6A modifications was screened. Afterwards, we successfully identified the targets that underwent m6A methylation mediated by METTL3, a methyltransferase-like enzyme. Last, we evaluated the regulatory role of METTL3-medited m6A methylation at phosphatase and tensin homolog (Pten) in ALI, by assessing the proliferation, viability and inflammation of AECII. RESULTS: LPS induced marked damages in respiratory functions and cellular injuries of AECII. The m6A modification level in mRNA and the expression of METTL3, an m6A methyltransferase, exhibited a notable rise in both lung tissues of ALI mice and cultured AECII cells subjected to LPS treatment. METTL3 knockdown or inhibition improved the viability and proliferation of LPS-treated AECII, and also reduced the m6A modification level. In addition, the stability and translation of Pten mRNA were enhanced by METTL3-mediated m6A modification, and over-expression of PTEN reversed the protective effect of METTL3 knockdown in the LPS-treated AECII. CONCLUSIONS: The progression of ALI can be attributed to the elevated levels of METTL3 in AECII, as it promotes the stability and translation of Pten mRNA through m6A modification. This suggests that targeting METTL3 could offer a novel approach for treating ALI.

Optimal surgical timing for lung cancer following SARS-CoV-2 infection: a prospective multicenter cohort study.

BACKGROUND: With the ongoing prevalence of the emerging variant and global vaccination efforts, the optimal surgical timing for patients with resectable lung cancer in the Omicron-dominant period requires further investigation. METHODS: This prospective multicenter study involved patients who underwent radical surgery for lung cancer between January 29, 2023 and March 31, 2023. Patients were categorized into four groups based on the interval between SARS-CoV-2 infection and surgery. The main outcomes evaluated were 30-day mortality and 30-day morbidity. RESULTS: A total of 2081 patients were enrolled in the study, of which 1837 patients (88.3%) had a confirmed SARS-CoV-2 diagnosis before surgery. Notably, no instances of 30-day mortality were observed in any patient. Patients without prior infection had a 30-day morbidity rate of 15.2%, with postoperative pneumonia occurring in 7.0% of cases. In contrast, patients diagnosed with SARS-CoV-2 before surgery had significantly higher rates of 30-day morbidity and postoperative pneumonia when surgery was performed within 4-5 weeks (adjusted odds ratio (aOR) (95% CI):2.18 (1.29-3.71) and 2.39 (1.21-4.79), respectively) or within 6-7 weeks (aOR (95% CI):2.07 (1.36-3.20) and 2.10 (1.20-3.85), respectively). Conversely, surgeries performed ≥ 8 weeks after SARS-CoV-2 diagnosis exhibited similar risks of 30-day morbidity and pneumonia compared to those in the no prior infection group (aOR (95% CI):1.13 (0.77-1.70) and 1.12 (0.67-1.99), respectively). CONCLUSIONS: Thoracic surgery for lung cancer conducted 4-7 weeks after SARS-CoV-2 infection is still associated with an increased risk of 30-day morbidity in the Omicron-dominant period. Therefore, surgeons should carefully assess the individual risks and benefits to formulate an optimal surgical strategy for patients with lung cancer with a history of SARS-CoV-2 infection.

Mechanisms of Hydrophobic Recovery of Poly(dimethylsiloxane) Elastomers after Plasma/Corona Treatments: A Minireview.

Plasma/corona treatment could alter the wettability of a poly(dimethylsiloxane) (PDMS) surface from being hydrophobic to being hydrophilic, which has attracted many researchers' attention. However, the treated surface will gradually recover its hydrophobicity as it ages. To understand the recovery, many studies have been performed. Although there is still no general consensus on the recovery mechanisms, several models have been proposed that can explain the reported wetting behavior of hydrophobic recovery. In this minireview, we summarized the reported mechanisms underlying the hydrophobicity-recovery of oxidized PDMS surfaces, which are certainly affected by varied factors including temperature, aging time, stored conditions, and treatment conditions. We hope this minireview can give beginners in the field of microfluidics a better understanding on the various mechanisms that contribute to the hydrophobic recovery of PDMS surfaces and thus take appropriate measures to efficiently maintain the surface wettability of oxidized PDMS chips to prolong their performance.

Efficient Removal of Iodine from Water by a Calix[4]pyrrole-Based Nanofilm.

The efficient removal of radioactive iodine from an aqueous solution is largely dependent on the adsorbent materials employed. In this work, we report a calix[4]pyrrole-based nanofilm and its application for the rapid removal of iodine from water. The nanofilm was synthesized through a confined dynamic condensation of tetra hydrazide calix[4]pyrrole with 1,3,5-tri-(4-formylphenyl) aldehyde at the air/dimethyl sulfoxide (DMSO) interface. The thickness of the obtained nanofilm is ∼35 nm, enabling fast mass transfer and a high ratio of accessible binding sites for iodine. The pseudo-second-order rate constant of the nanofilm for iodine is ∼0.061 g g-1 min-1, 3 orders of magnitude higher than most reported adsorbent materials. Flow-through nanofiltration tests demonstrated that the nanofilm has an adsorption capacity of 1.48 g g-1, a high removal efficiency, and good reusability. The mechanism study revealed that the moieties of Schiff base, pyrrole, and aromatic rings play a key role for binding iodine. We believe this work provides not only a new strategy for the efficient removal of radioactive iodine from water but also new ideas for designing efficient iodine adsorbents.

Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVE: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.

A Sn-Based Hybrid Ferroelastic Semiconductor with High-Temperature Dielectric Switching.

Organic-inorganic halide hybrids have been extensively developed and used in optoelectronic devices because of their superior performance such as ease of assembly, flexible structural tunability, and excellent optoelectronic properties. Ferroelastic strain might be used to modulate and control photoelectric properties such as photovoltaic voltage, while organic-inorganic hybrid ferroelastic semiconductors remain relatively unexplored. Herein, we successfully design a new Sn-base, lead-free hybrid ferroelastic semiconductor, [TPMA]2[SnCl6] (TPMA = benzyl trimethylammonium). It undergoes a high-temperature -3mF-1-type ferroelastic phase transition at 408 K, and intriguingly, its ferroelastic domains can be simultaneously switched under the stimulation of external heat and stress. The ferroelastic phase transition might be derived from the order-disorder transition of organic cations during heating and cooling. Moreover, [TPMA]2[SnCl6] also demonstrates a high-temperature dielectric switching property around 408 K, which has good stability and reproducibility. With those benefits, [TPMA]2[SnCl6] shows great potential in applications such as energy storage devices, optoelectronic devices, shape memory, intelligent switches, and so on.