Sleep Duration and Functional Disability among Chinese Older Adults: A Cross-Sectional Study.

BACKGROUND: Duration of sleep has a crucial role in the development of physiological functions that impact health. Little is known about the associations between sleep duration and functional disability among the older adults in China. OBJECTIVE: This study aims to explore the associations between sleep duration and functional disabilities in the older population aged 65 years and above in China. METHODS: The data for this cross-sectional study were gathered from respondents aged 65 years and above who participated in the 2018 survey of China Health and Retirement Longitudinal Study, an ongoing nationwide longitudinal investigation of Chinese adults. The duration of sleep per night was obtained through face-to-face interviews. Functional disability was assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL). The association between sleep duration and functional disability was assessed by multivariable generalized linear model. Restricted cubic spline model was used to explore the dose-response relationship between sleep duration and functional disability. RESULTS: In total, 5 519 participants [Male: 2 471 (44.77%)] were included in this study with a mean age of 73.67 years old, containing 2 800 (50.73%) functional disabled, 1 978 (35.83%) ADL disabled, and 2 299 (41.66%) IADL disabled older adults. After adjusted for potential confounders, individuals reported shorter sleep durations (≤ 4, 5, 6 hours) or longer sleep durations (8, 9, ≥ 10 hours) per night exhibited a notably increased risk of functional disability compared to those who with 7 hours (P < 0.05), which revealed a U-shape association between sleep duration and dysfunction. When sleep duration fell below 7 h, increased sleep duration was associated with a significantly lower risk of functional disability (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.79-0.91; P < 0.001). When sleep duration exceeded 7 h, the risk of functional disability (OR, 1.16; 95% CI, 1.05-1.29; P < 0.001) would increase facing prolonged sleep duration. CONCLUSIONS: Shorter and longer sleep duration was associated with a higher risk of functional disability among the aged 65 and above Chinese adults. Future studies are needed to explore intervention strategies about sleep duration especially focus on functional disability.

Effectiveness and Safety of Different Methods of Assisted Fat Grafting: A Network Meta-Analysis.

OBJECTIVE: Numerous studies have proposed the utilization of stromal vascular fraction (SVF), adipose-derived stem cells (ADSCs), and platelet products as auxiliary grafting techniques to improve the survival rate of fat grafts. This study aimed to evaluate the efficacy and safety of various fat grafting methods since 2010 through a network meta-analysis, aiming to identify the most effective technique for fat grafting. METHODS: Clinic trials on assisted fat grafting were searched from Pubmed, Embase, Web of Science, and the Cochrane Library, spanning the period from January 1, 2010 to March 2024. The risk of bias in the included trials was meticulously assessed using the Cochrane risk of bias tool. The survival rate of fat grafts served as the primary evaluation metric for effectiveness, while complications were employed as the indicator for safety. RESULTS: The study incorporated 31 clinic trials, involving a total of 1656 patients. The findings indicated that the survival rate with assisted fat grafting significantly surpassed that of simple fat grafting (SUCRA, 10.43%). Notably, ADSC-assisted fat grafting exhibited the highest survival rate (SUCRA, 82.17%), followed by Salvia miltiorrhiza (SM)-assisted fat grafting (SUCRA, 69.76%). In terms of safety, the most prevalent complications associated with fat grafting were fat sclerosis and fat necrosis. Adc-assisted fat grafting was correlated with the lowest incidence of complications (SUCRA, 41.00%), followed by simple fat grafting (SUCRA, 40.99%). However, PRP-assisted (SUCRA, 52.86%) and SVF-assisted fat grafting (SUCRA, 65.14%) showed higher complication rates. CONCLUSION: Various methods of assisted fat grafting can significantly enhance the survival rate, but they often fail to effectively mitigate the incidence of complications. Compared to other methods, adipose mesenchymal stem cells-assisted fat grafting consistently yielded a higher survival rate of grafts and fewer complications. Consequently, this approach represents a relatively effective method for assisting in fat grafting at present. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ovotransferrin Fibril-Gum Arabic Complexes as Stabilizers for Oleogel-in-Water Pickering Emulsions: Formation Mechanism, Physicochemical Properties, and Curcumin Delivery.

This project aimed to explore the influence of the interaction between ovotransferrin fibrils (OTF) and gum arabic (GA) on the formation mechanism, physicochemical properties, and curcumin delivery of the oleogel-in-water Pickering emulsion. Cryo-scanning electron microscopy results showed that OTF-GA complexes effectively adsorbed on the oil-water interface, generating spatial hindrance to inhibit droplet coalescence. The texture analysis also proved that OTF-GA complexes endowed oleogel-in-water Pickering emulsion with preferable springiness (0.49 ± 0.03 mm), chewiness (0.43 ± 0.07 mJ), and adhesion (0.31 ± 0.01 mJ). By exploring the coalescence stability, droplet size, and rheological properties of OTF-GA complexes-stabilized oleogel-in-water Pickering emulsion (OGPE), the higher coagulation stability, larger average droplet size (46.22 ± 0.08 µm), and stronger gel strength were observed. The microrheological results also exhibited stronger attraction between the OGPE droplets, a more pronounced solid-like structure, and a slower speed of movement than OTF-stabilized oleogel-in-water Pickering emulsion (OPE). Meanwhile, OGPE significantly enhanced the extent of lipolysis, stability, and bioaccessibility of curcumin, suggesting that it possessed superior performance as a delivery system for bioactive substances. This project provided adequate theoretical references for protein-polysaccharide complexes-stabilized oleogel-in-water Pickering emulsion, and contributed to expanding the application of oleogel-in-water Pickering emulsion in the food industry.

Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis.

Sepsis is defined as a dysregulated host response to infection that leads to multiorgan failure. Innate immune memory, i.e., "trained immunity", can result in stronger immune responses and provide protection against various infections. Many biological agents, including ß-glucan, can induce trained immunity, but these stimuli may cause uncontrolled inflammation. Oroxylin A (OA) is an active flavonoid compound that is derived from Scutellaria baicalensis. OA is an agonist for inducing trained immunity in vivo and in vitro, and ß-glucan was used as a positive control. The protective effects of OA-induced trained immunity were evaluated in mouse models that were established by either lipopolysaccharide (LPS) administration or caecal ligation and puncture (CLP). The expression of inflammatory factors and signaling pathway components involved in trained immunity was evaluated in vitro using qRT‒PCR, western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Flow cytometry and confocal microscopy were used to examine reactive oxygen species (ROS) levels and phagocytosis in trained macrophages. A PCR array was used to screen genes that were differentially expressed in trained macrophages. Here, we revealed that OA alleviated sepsis via trained immunity. OA-treated macrophages displayed increased glycolysis and mTOR phosphorylation, and mTOR inhibitors suppressed OA-induced trained immunity by effectively reprogramming macrophages. The PCR array revealed key genes in the mTOR signaling pathway in OA-treated macrophages. Furthermore, OA targeted the Dectin-1-syk axis to promote LC3-associated phagocytosis (LAP) by trained macrophages, thereby enhancing the ability of these macrophages to protect against infection. This ability could be transferred to a new host via the adoptive transfer of peritoneal macrophages. This study is the first to provide new insights into the potential of OA-induced trained immunity to be used as a strategy to protect mice against sepsis by promoting LAP by macrophages.

MSCs promote the efferocytosis of large peritoneal macrophages to eliminate ferroptotic monocytes/macrophages in the injured endometria.

BACKGROUND: Endometria are one of the important components of the uterus, which is located in the peritoneal cavity. Endometrial injury usually leads to intrauterine adhesions (IUA), accompanied by inflammation and cell death. We previously reported that both the endometrial ferroptosis was increased and monocytes/macrophages were involved in endometrial injury of IUA. Large peritoneal macrophages (LPMs) are recently reported to migrate into the injured tissues and phagocytose dead cells to repair the tissues. We previously demonstrated that mesenchymal stromal cells (MSCs) had made excellent progress in the repair of endometrial injury. However, it is unclear whether MSCs regulate the LPM efferocytosis against ferroptotic monocytes/macrophages in the injured endometria. METHODS: Here, endometrial injury in IUA mouse model was conducted by uterine curettage and LPS injection surgery and the samples were collected at different times to detect the changes of LPMs and ferroptotic monocytes/macrophages. We conducted LPMs depletion assay in vivo and LPMs and Erastin-induced ferroptotic THP-1 cells coculture systems in vitro to detect the LPM efferocytosis against ferroptotic monocytes/macrophages. The IUA model was treated with MSCs, and their effects on LPMs and endometrial repair were analyzed. Flow cytometry, western blotting, quantitative real-time PCR, immunohistochemical analysis, ELISA, and RNA-sequencing were performed. RESULTS: We found that LPMs migrated to the injured uteri in response to the damage in early phase (3 h), and sustained to a later stage (7 days). Astonishingly, we found that ferroptotic monocytes/macrophages were significantly increased in the injured uteri since 12 h after injury. Moreover, LPMs cocultured with Erastin-induced ferroptotic THP-1 cells in vitro, efferocytosis of LPMs against ferroptotic monocytes/macrophages was emerged. The mRNA expression profiles revealed that LPM efferocytosis against ferroptotic monocytes/macrophages was an induction of glycolysis program and depended on the PPARγ-HK2 pathway. Importantly, we validated that MSCs promoted the efferocytic capability and migration of LPMs to the injured uteri via secreting stanniocalcin-1 (STC-1). CONCLUSION: The data collectively demonstrated first the roles of LPMs via removal of ferroptotic monocytes/macrophages and provided a novel mechanism of MSCs in repairing the endometrial injury.

Reconfiguring the Hydrogen Networks of Aqueous Electrolyte to Stabilize Iron Hexacyanoferrate for High-Voltage Decoupled Cell.

Prussian blue analogs (PBAs) as insertion-type cathodes have attracted significant attention in various aqueous batteries to accommodate metal or non-metal ions while suffering from serious dissolution and consequent inferior lifespan. Herein, we reveal that the dissolution of PBAs primarily originates from the locally elevated pH of electrolytes that are caused by proton co-insertion during discharge. To address this issue, a water-locking electrolyte (WLE) has been strategically implemented, which interrupts the generation and Grotthuss diffusion of protons by breaking the well-connected hydrogen bonding network in aqueous electrolytes. As a result, the WLE enables the iron hexacyanoferrate to endure over 1000 cycles at a 1C rate and supports a high-voltage decoupled cell with an average voltage of 1.95 V. These findings provide insights for mitigating dissolution problems in electrode materials, thereby enhancing the viability and performance of aqueous batteries.

Upf2-Mediated Nonsense-Mediated Degradation Pathway Involved in Genetic Compensation of TrpA1 Knockout Mutant Silkworm (Bombyx mori).

Genetic mutations leading to premature termination codons are known to have detrimental effects. Using the Lepidoptera model insect, the silkworm (Bombyx mori), we explored the genetic compensatory response triggered by mutations with premature termination codons. Additionally, we delved into the molecular mechanisms associated with the nonsense-mediated mRNA degradation pathway. CRISPR/Cas9 technology was utilized to generate a homozygous bivoltine silkworm line BmTrpA1-/- with a premature termination. Transcript levels were assessed for the BmTrpA paralogs, BmPyrexia and BmPainless as well as for the essential factors Upf1, Upf2, and Upf3a involved in the nonsense-mediated mRNA degradation (NMD) pathway. Upf2 was specifically knocked down via RNA interference at the embryonic stage. The results comfirmed that the BmTrpA1 transcripts with a 2-base deletion generating a premature termination codon in the BmTrpA1-/- line. From day 6 of embryonic development, the mRNA levels of BmPyrexia, BmPainless, Upf1, and Upf2 were significantly elevated in the gene-edited line. Embryonic knockdown of Upf2 resulted in the suppression of the genetic compensation response in the mutant. As a result, the offspring silkworm eggs were able to hatch normally after 10 days of incubation, displaying a non-diapause phenotype. It was observed that a genetic compensation response does exist in BmTrpA1-/-B. mori. This study presents a novel discovery of the NMD-mediated genetic compensation response in B. mori. The findings offer new insights into understanding the genetic compensation response and exploring the gene functions in lepidopteran insects, such as silkworms.

Analysis of Ileal Atresia from Prenatal Ultrasound to Postoperative Follow-up: Two Case Reports.

BACKGROUND: Congenital ileal atresia is a rare neonatal disease, the most common type of intestinal malformation in newborns, and one of the most common causes of congenital intestinal obstruction. It can cause various digestive system symptoms, including abdominal distension, vomiting, abnormal bowel movements, etc. In severe cases, it can be life-threatening. A prenatal ultrasound examination can assist clinical diagnosis of congenital ileal atresia, and those with a clear prenatal diagnosis should undergo surgical treatment after birth. CASE PRESENTATION: We have, herein, reported two cases of congenital ileal atresia, both of which showed fetal intestinal dilation (>7mm) and excessive amniotic fluid on prenatal ultrasound. Both newborns underwent surgical treatment after delivery and were confirmed to have congenital ileal atresia during surgery. Due to the different prenatal ultrasound manifestations of the two patients, they were divided into two different subtypes based on intraoperative manifestations. We observed significant differences in the prognosis of the two patients after surgery. CONCLUSION: Accurately locating and classifying ileal atresia using prenatal ultrasound is challenging; however, it plays an effective role in disease progression, gestational assessment, and prognosis. Accurately identifying intestinal diseases and/or the location of lesion sites through direct and indirect ultrasound findings in the fetal abdominal cavity is an important research direction for prenatal ultrasound.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs.

Although the selective and effective clearance of senescent cancer cells can improve cancer treatment, their development is confronted by many challenges. As part of efforts designed to overcome these problems, prodrugs, whose design is based on senescence-associated ß-galactosidase (SA-ß-gal), have been developed to selectively eliminate senescent cells. However, chemotherapies relying on targeted molecular inhibitors as senolytic drugs can induce drug resistance. In the current investigation, we devised a new strategy for selective degradation of target proteins in senescent cancer cells that utilizes a prodrug composed of the SA-ß-gal substrate galactose (galacto) and the proteolysis-targeting chimeras (PROTACs) as senolytic agents. Prodrugs Gal-ARV-771 and Gal-MS99 were found to display senolytic indexes higher than those of ARV-771 and MS99. Significantly, results of in vivo studies utilizing a human lung A549 xenograft mouse model demonstrated that concomitant treatment with etoposide and Gal-ARV-771 leads to a significant inhibition of tumor growth without eliciting significant toxicity.

Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.

A Rotating Cathode with Periodical Changes in Electrolyte Layer Thickness for High-Rate Li‒O2 Batteries.

Li-O2 batteries (LOBs) possess the highest theoretical gravimetric energy density among all types of secondary batteries, but they are still far from practical applications. The poor rate performance resulting from the slow mass transfer is one of the primary obstacles in LOBs. To solve this issue, a rotating cathode with periodic changes in the electrolyte layer thickness is designed, decoupling the maximum transfer rate of Li+ and O2. During rotation, the thinner electrolyte layer on the cathode facilitates the O2 transfer, and the thicker electrolyte layer enhances the Li+ transfer. As a result, the rotating cathode enables the LOBs to undergo 58 cycles at 2.5 mA cm-2 and discharge stably even at a high current density of 7.5 mA cm-2. Besides, it also makes the batteries exhibit a large discharge capacity of 6.8 mAh cm-2, and the capacity decay is much slower with increasing current density. Notably, this rotating electrode holds great promise for utilization in other electrochemical cells involving gas-liquid-solid triple-phase interfaces, suggesting a viable approach to enhance the mass transfer in such systems.

Positive effects of parent-child group emotional regulation and resilience training on nonsuicidal self-injury behavior in adolescents: a quasi-experimental study.

Background: Nonsuicidal self-injury (NSSI) among adolescents is a growing global concern. However, effective interventions for treating NSSI are limited. Method: A 36-week quasi-experimental study design of parent-child group resilience training (intervention group) for adolescents aged 12-17 years was used and compared with treatment-as-usual (control group). The primary endpoint was the frequency of NSSI assessed with the Ottawa Self-Injury Inventory (OSI), and the secondary endpoints were the levels of depression, hope, resilience, and family adaptability and cohesion as assessed by the 24-item Hamilton depression rating scale (HAMD-24), Herth Hope Scale (HHS), Connor-Davidson Resilience Scale (CD-RISC), and Family Adaptability and Cohesion Evaluation Scale, second edition (FACES-II-CV), respectively. Result: A total of 118 participants completed the trial. Both groups showed a significant reduction in NSSI frequency after 12, 24, and 36 weeks of intervention (p< 0.05), although the intervention group did not differ significantly from the control group. After 12, 24, and 36 weeks of intervention, the CD-RISC, HHS, HAMD-24, and FACES-II-CV scores in the intervention and control groups improved over baseline (p< 0.05). Furthermore, the intervention group had higher scores on the CD-RISC, HHS, and FACES-II-CV and lower scores on the HAMD-24 than the control group after 12, 24, and 36 weeks of intervention (p  < 0.05). Conclusion: Parent-child group emotional regulation and resilience training showed promise as treatment options for NSSI among adolescents, leading to increased hope, resilience, and improved family dynamics among NSSI teens. Moreover, NSSI frequency significantly decreased in the intervention group compared to baseline.

Identification and Verification of Ferroptosis-Related Genes in Keratoconus Using Bioinformatics Analysis.

Objective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics. Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues. Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group. Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.

Risk factors associated with false negative rate of sentinel lymph node biopsy in endometrial cancer: a systematic review and meta-analysis.

Objective: Currently, sentinel lymph node biopsy (SLNB) is increasingly used in endometrial cancer, but the rate of missed metastatic lymph nodes compared to systemic lymph node dissection has been a concern. We conducted a systematic review and meta-analysis to evaluate the false negative rate (FNR) of SLNB in patients with endometrial cancer and to explore the risk factors associated with this FNR. Data sources: Three databases (PubMed, Embase, Web of Science) were searched from initial database build to January 2023 by two independent reviewers. Research eligibility criteria: Studies were included if they included 10 or more women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I or higher endometrial cancer, the study technique used sentinel lymph node localization biopsy, and the reported outcome metrics included false negative and/or FNR. Study appraisal and synthesis methods: Two authors independently reviewed the abstracts and full articles. The FNR and factors associated with FNR were synthesized through random-effects meta-analyses and meta-regression. The results: We identified 62 eligible studies. The overall FNR for the 62 articles was 4% (95% CL 3-5).There was no significant difference in the FNR in patients with high-risk endometrial cancer compared to patients with low-risk endometrial cancer. There was no difference in the FNR for whether frozen sections were used intraoperatively. The type of dye used intraoperatively (indocyanine green/blue dye) were not significantly associated with the false negative rate. Cervical injection reduced the FNR compared with alternative injection techniques. Indocyanine green reduced the FNR compared with alternative Tc-99m. Postoperative pathologic ultrastaging reduced the FNR. Conclusions: Alternative injection techniques (other than the cervix), Tc-99m dye tracer, and the absence of postoperative pathologic ultrastaging are risk factors for a high FNR in endometrial cancer patients who undergo SLNB; therefore, we should be vigilant for missed diagnosis of metastatic lymph nodes after SLNB in such populations. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023433637.

Dynamic immobilization of bacterial cells on biofilm in a polyester nonwoven chemostat.

Cell immobilization plays an important role in biocatalysis for high-value products. It is necessary to maintain the viability of immobilized cells for bioconversion using viable cells as biocatalysts. In this study, a novel polyester nonwoven chemostat was designed for cell immobilization to investigate biofilm formation and the dynamic balance between adsorption and desorption of cells on polyester nonwoven. The polyester nonwoven was suitable for cell immobilization, and the cell numbers on the polyester nonwoven can reach 6.5 ± 0.38 log CFU/mL. After adding the polyester nonwoven to the chemostat, the fluctuation phenomenon of free bacterial cells occurred. The reason for this phenomenon was the balance between adsorption and desorption of bacterial cells on the polyester nonwoven. Bacterial cells could adhere to the surface of polyester nonwoven via secreting extracellular polymeric substances (EPS) to form biofilms. As the maturation of biofilms, some dead cells inside the biofilms can cause the detachment of biofilms. This process of continuous adsorption and desorption of cells can ensure that the polyester nonwoven chemostat has lasting biological activity.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Disruption in CYLC1 leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice.

The perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an 'IAM-cylicins-NE' sandwich structure, anchoring the acrosome to the nucleus. WES (whole exome sequencing) of more than 500 Chinese infertile men with sperm head deformities was performed and a CYLC1 variant was identified in 19 patients. Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that this CYLC1 variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring the CYLC1 variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome-nucleus connection and suggest CYLC1 variants as potential risk factors for human male fertility.

Last Glacial Maximum pattern effects reduce climate sensitivity estimates.

Here, we show that the Last Glacial Maximum (LGM) provides a stronger constraint on equilibrium climate sensitivity (ECS), the global warming from increasing greenhouse gases, after accounting for temperature patterns. Feedbacks governing ECS depend on spatial patterns of surface temperature ("pattern effects"); hence, using the LGM to constrain future warming requires quantifying how temperature patterns produce different feedbacks during LGM cooling versus modern-day warming. Combining data assimilation reconstructions with atmospheric models, we show that the climate is more sensitive to LGM forcing because ice sheets amplify extratropical cooling where feedbacks are destabilizing. Accounting for LGM pattern effects yields a median modern-day ECS of 2.4°C, 66% range 1.7° to 3.5°C (1.4° to 5.0°C, 5 to 95%), from LGM evidence alone. Combining the LGM with other lines of evidence, the best estimate becomes 2.9°C, 66% range 2.4° to 3.5°C (2.1° to 4.1°C, 5 to 95%), substantially narrowing uncertainty compared to recent assessments.