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Although scholars have researched Chinese parents' perspectives on play pedagogy, few investigate the differences between parents of preschoolers and early primary schoolers, non-immigrant and immigrant parents. The present study employs the theoretical framework of parental ethnotheories to describe parental understanding and concerns about the use of play in supporting young children's English learning in China. The nine participants included parents of preschoolers and/or primary schoolers who were non-immigrant and immigrant Chinese parents in Canada. Findings revealed different types of discrepancies concerning parental beliefs and practices. First, there was a gap between parents' beliefs and their practices regarding child-rearing and education. Second, in terms of understanding play, Chinese parents held a slightly different perspective compared to that of western parents in other studies, showing that Chinese parents only valued play's supporting role in the development of non-cognitive aspects, such as improving interest in learning English. Third, parents of preschoolers and early primary schoolers held conflicting attitudes toward the use of play in children's learning. Fourth, immigrant Chinese parents were inclined to follow traditional Chinese notions of child-rearing, revealing discrepant perceptions about child play and rearing compared to western knowing of child-rearing in previous studies. The findings raise implications for educators to balance the pedagogical perspectives of child development and parental ethnotheories of child development.

Abstract Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.

To further enhance the mechanical properties and service temperature of silicone resin coatings， the effects of the silane coupling agent KH-560 and low melting point glass powder on the thermal protection performance of silicone resin coatings were investigated.The elastic modulus， bonding strength， thermal expansion coefficient， ablation， thermal insulation and thermal shock properties of the coating were tested using a high-temperature solid material dynamic elastic property tester， a universal electronic tensile machine， an expansion meter and a gas thermal shock experimental system； The composition， surface micromorphology and elemental content of the coating were analyzed using infrared spectroscopy， emission scanning electron microscopy， and its attached energy spectrum analysis.Results showed that with increasing KH-560 content (0～3%)， the elastic modulus and adhesion strength of the silicone resin coatings were initially increased and then decreased.When 2.0%KH-560 was added，the maximum values for the elastic modulus and adhesion strength of the coatings were achieved at room temperature， reaching 24.10 GPa and 4.40 MPa， respectively.This was mainly attributed to the enhancement of bonding between the silicone resin and the metal substrate， as well as between the filler and the silicone resin facilitated by KH-560.The addition of 110%glass powder was found to effectively improve the thermal stability and thermal shock resistance of the silicone resin coatings at 800 ℃， due to the melting of glass powder，which filled the voids generated by the decomposition of silicone resin， thereby preventing further oxidation decomposition of the silicone resin.Additionally， silicone resin coatings with a glass powder content of 110%were observed to exhibit good thermal insulation and ablative properties.

Abstract Currently, the treatment of miscellaneous fill foundations, composed of a mixture of domestic garbage, construction solid waste, and natural soil, presents a significant challenge in urban peripheral engineering construction. This paper discusses the application of vibrating rod compaction technology for foundation treatment in Xinjiang. It evaluates the effectiveness of cross-section vibrating rod compaction equipment in reinforcing fine-grained miscellaneous fill foundations. The study analyzes the impact of construction disturbances caused by the insertion of the vibrating rod, monitoring horizontal stresses at various depths. Both laboratory and field tests show significant improvements: soil dry density increased by 8% to 18%, porosity decreased by 10% to 23%, compression modulus increased by 22% to 246%, and compression coefficient decreased by 8% to 70%. Additionally, cohesion (C) and angle of friction (ɸ) saw increases ranging from 7 to 38% and 3% to 25%, respectively. Below a depth of 3 m, cone tip resistance exceeded 10 MPa, and sidewall friction resistance increased to over 100 kPa, surpassing pre-treatment values. The standard penetration test results doubled stroke length compared to pre-treatment, indicating a substantial improvement in foundation bearing capacity. Surface wave tests before and after treatment showed a 15% increase in wave velocity, reflecting a more compact soil structure. The vibrating rod compaction method is innovative, energy-efficient, environmentally friendly, and economically beneficial, holding great potential for future miscellaneous fill treatments.

Abstract Anal swabs of 1-month-old Holstein calves with diarrhea were collected from an intensive cattle farm, and a highly pathogenic Escherichia coli strain was obtained by isolation and purification. To study the virulence and resistance genes of pathogenic E. coli that cause diarrhea in calves, a strain of E. coli E12 isolated from calf diarrhea samples was used as experimental material in this experiment, and the virulence of the E12 strain were identified by the mouse infection test, and the whole genome map of the E12 strain were obtained by whole-genome sequencing and analyzed for genome characterization. The results showed that the lethality of strain E12 was 100%, the total length of E12-encoded genes was 4,294,530 bp, Cluster of Orthologous Groups of proteins (COG) annotated to 4,194 functional genes, and the virulence genes of sequenced strain E12 were compared with the virulence genes of sequenced strain E12 from the Virulence Factors of Pathogenic Bacteria (VFDB), which contained a total of 366 virulence genes in sequenced strain E12. The analysis of virulence genes of E12 revealed a total of 52 virulence genes in the iron transferrin system, 56 virulence genes in the secretory system, 41 virulence genes in bacterial toxins, and a total of 217 virulence genes in the Adhesin and Invasins group. The antibiotic resistance genes of sequenced strain E12 were identified through the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Research Database, and it was found that its chromosome and plasmid included a total of 127 antibiotic resistance genes in four classes, and that E12 carried 71 genes related to the antibiotic efflux pumps, 36 genes related to antibiotic inactivation, and 14 antibiotic target alteration and reduced penetration into antibiotics, and 6 antibiotic resistance genes, and the resistance phenotypes were consistent with the genotypes. The pathogenic E. coli that causes diarrhea in calves on this ranch contains a large number of virulence and resistance genes. The results provide a theoretical basis for the prevention and treatment of diarrhea and other diseases caused by E. coli disease.

Abstract Graphene has been extensively utilized as an electrode material for nonaqueous electrochemical capacitors. However, a comprehensive understanding of the charging mechanism and ion arrangement at the graphene/electrolyte interface remain elusive. Herein, a gap-enhanced Raman spectroscopic strategy is designed to characterize the dynamic interfacial process of graphene with an adjustable number of layers, which is based on synergistic enhancement of localized surface plasmons from shell-isolated nanoparticles and a metal substrate. By employing such a strategy combined with complementary characterization techniques, we study the potential-dependent configuration of adsorbed ions and capacitance curves for graphene based on the number of layers. As the number of layers increases, the properties of graphene transform from a metalloid nature to graphite-like behavior. The charging mechanism shifts from co-ion desorption in single-layer graphene to ion exchange domination in few-layer graphene. The increase in area specific capacitance from 64 to 145 µF cm –2 is attributed to the influence on ion packing, thereby impacting the electrochemical performance. Furthermore, the potential-dependent coordination structure of lithium bis(fluorosulfonyl) imide in tetraglyme ([Li(G4)][FSI]) at graphene/electrolyte interface is revealed. This work adds to the understanding of graphene interfaces with distinct properties, offering insights for optimization of electrochemical capacitors.

Abstract Carbolong complexes are one of the primary types of metallaaromatics, and they include metallapentalynes and metallapentalenes. A series of 7C-10C and 12C-carbolong complexes with planar ligand skeletons respectively containing 7-10 and 12 carbon atoms in their backbones, have been previously reported. Herein, two classes of strained substances, metallabenzyne-fused metallapentalenes and metallabenzene-fused metallapentalynes, were prepared, both representing 11C-carbolong complexes with a planar carbon-chain ligand. Furthermore, the former type is also the carbolong derivatives containing a metallabenzyne skeleton, another primary metallaaromatic framework. Metallabenzyne-fused metallapentalenes show versatile reactivities, and the most interesting one is the metal carbyne bond shift from a 6-membered to a more strained 5-membered ring, affording the above-mentioned metallabenzene-fused metallapentalyne. This work makes carbolong chemistry more complete, and provides a method to achieve metallabenzynes, which is anticipated to concurrently advance the development of these two types of metallaaromatics.

BackgroundAlpha-synuclein oligomers (o-α-syn) are pivotal in the pathogenesis of α-synucleinopathy. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) serves as an early indicator of the disease, offering insights into disease mechanisms and early intervention. Nevertheless, the diagnostic and predictive potential of o-α-syn in iRBD remains largely unexplored. This study aimed to evaluate the plasma levels of o-α-syn in patients and investigate their utility as biomarkers for diagnosis of and predicting phenoconversion in iRBD.MethodsA total of 143 participants, including 77 polysomnography-confirmed iRBD patients and 66 normal controls (NC), were recruited for this longitudinal observational study. Baseline clinical assessments and plasma collection were conducted for all iRBD patients, with 72 of them undergoing regularly prospective follow-up assessments for parkinsonism or dementia. Plasma levels of o-α-syn were quantified using enzyme-linked immunosorbent assay, and were compared between groups using a general linear model adjusted for age and sex. The diagnostic performance of plasma o-α-syn in iRBD was evaluated by area under the receiver operating characteristic curve (AUC) with 95% CI. Cox regression analysis and Kaplan–Meier survival curves were employed to assess the predictive value of plasma o-α-syn for phenoconversion in iRBD.ResultsPlasma o-α-syn levels did not exhibit statistically significant differences among iRBD converter patients, iRBD nonconverter patients, and NC. The AUC for distinguishing NC from iRBD was 0.52 (95% CI: 0.42–0.62, p = 0.682). Spearman correlation analysis revealed a significant positive correlation between plasma o-α-syn levels and MOCA scores in the iRBD group (p

Abstract Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol‐carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)‐4‐carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near‐infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH‐dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti‐programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF‐FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI‐guided targeted therapeutic pathways for tumors.

BackgroundPaBing-II Formula (PB-II) is a traditional Chinese medicine for treating Parkinson’s disease (PD). However, owing to the complexity of PB-II and the difficulty in obtaining human dopaminergic neurons (DAn), the mechanism of action of PB-II in PD treatment remains unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic benefits of PB-II in patients with PD.MethodshiPSCs derived DAn were treated with H2O2 to construct the DAn oxidative damage model. SwissTargetPrediction was employed to predict the potential targets of the main compounds in serum after PB-II treatment. Metascape was used to analyze the pathways. Sprague-Dawley rats were used to construct the 6-hydroxydopamine (6-OHDA)-induced PD model, and the duration of administration was four weeks. RNA sequencing was used for Transcriptome analysis to find the signal pathways related to neuronal damage. The associated inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). We identified PB-II as an Nrf2 activator using antioxidant-responsive element luciferase assay in MDA-MB-231 cells.ResultsIn vitro experiments showed that the treatment of PB-II-treated serum increased the percentage of TH+ cells, decreased inflammation and the apoptosis, reduced cellular reactive oxygen species, and upregulated the expression of Nrf2 and its downstream genes. Pathway analysis of the RNA-seq data of samples before and after the treatment with PB-II-treated serum identified neuron-associated pathways. In vivo experiments demonstrated that PB-II treatment of PD rat model could activate the Nrf2 signaling pathway, protect the midbrain DAn, and improve the symptoms in PD rats.ConclusionPB-II significantly protects DAn from inflammation and oxidative stress via Nrf2 pathway activation. These findings elucidate the roles of PB-II in PD treatment and demonstrate the application of hiPSC-derived DAn in research of Chinese medicine.

White light emitting diodes (wLEDs) have been widely used as the green lighting sources. The commercial wLEDs devices are mainly achieved through the combination of blue emission chips and yellow phosphors, which offer advantages of high efficiency and long lifetime. However, the color rendering index (CRI) of traditional wLEDs is low due to the lack of red components. In recent years, with the improvement of the quality of life, a lot of efforts have been paid to improve the performance of wLEDs devices related to CRI, correlated color temperature, light uniformity, luminous flux, etc. In this article, we summarize the recent advances on the optimization of wLEDs toward healthy lighting. Brief introductions on the fundamentals of healthy effect of lighting are presented, followed by discussions of current methods to realize wLEDs devices. Special overviews on strategies for luminescent materials of wLEDs in recent years are presented. The opportunities and challenges in the future development of wLEDs lighting devices are also discussed.

Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia–reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury. Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining. Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury. Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.

Objective(MSU) crystals usually in the kidney tubules especially collecting ducts in the medulla. Previous animal models have not fully reproduced the impact of MSU on kidneys under non-hyperuricemic conditions.MethodsIn the group treated with MSU, the upper pole of the rat kidney was injected intrarenally with 50 mg/kg of MSU, while the lower pole was injected with an equivalent volume of PBS solution. The body weight and kidney mass of the rats were observed and counted. H&E staining was used to observe the pathological damage of the kidney and to count the number of inflammatory cells. Masoon staining was used to observe the interstitial fibrosis in the kidneys of the rat model. Flow cytometric analysis was used for counting inflammatory cells in rats. ElISA was used to measure the concentration of serum and urine uric acid, creatinine and urea nitrogen in rats.ResultsAt the MSU injection site, a significantly higher infiltration of inflammatory cells and a substantial increase in the area of interstitial fibrosis compared to the control group and the site of PBS injection were observed. The serum creatinine level was significantly increased in the MSU group. However, there were no significant differences in the rats’ general conditions or blood inflammatory cell counts when compared to the control group.ConclusionThe injection of urate crystals into the kidney compromised renal function, caused local pathological damage, and increased inflammatory cell infiltration and interstitial fibrosis. Intrarenal injection of MSU crystals may result in urate nephropathy. The method of intrarenal injection did not induce surgical infection or systemic inflammatory response.

Integrated Access and Backhaul (IAB) technology promises to facilitate cost-effective deployments of 5G New Radio (NR) systems operating in both sub-6 GHz and millimeter-wave (mmWave) bands. As full-duplex wireless systems are in their infancy, initial deployments of IAB networks may need to rely on half-duplex operation to coordinate transmissions between access and backhaul links. However, the use of half-duplex operation not only makes the scheduling of links in the IAB networks interdependent, but also the number of their feasible combinations grows exponentially with the network size, thereby posing challenges to the efficient design of such systems. In this paper, by accounting for mmWave radio characteristics, we propose a joint resource allocation and link scheduling framework to enhance the user equipment (UE) throughput in multi-hop in-band IAB systems. We keep the problem in the form of linear programming type for the feasibility of the practical applications. We show that the increased number of uplink and downlink transmission time interval (TTI) configurations does not result in improved UE throughput as compared to two-TTI configuration. Further, we demonstrate that in-band IAB systems tend to be backhaul-limited, and the utilization of multi-beam functionality at the IAB-donor alleviates this limitation by doubling the average UE throughput. Finally, we show that the use of proportional-fair allocations allows the average UE throughput to be improved by around 10% as compared to the max-min allocations.

Abstract Viruses, as opportunistic intracellular parasites, hijack the cellular machinery of host cells to support their survival and propagation. Numerous viral proteins are subjected to host-mediated post-translational modifications. Here, we demonstrate that the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is SUMOylated on the lysine 65 residue, which efficiently mediates SARS2-NP’s ability in homo-oligomerization, RNA association, liquid-liquid phase separation (LLPS). Thereby the innate antiviral immune response is suppressed robustly. These roles can be achieved through intermolecular association between SUMO conjugation and a newly identified SUMO-interacting motif in SARS2-NP. Importantly, the widespread SARS2-NP R203K mutation gains a novel site of SUMOylation which further increases SARS2-NP’s LLPS and immunosuppression. Notably, the SUMO E3 ligase TRIM28 is responsible for catalyzing SARS2-NP SUMOylation. An interfering peptide targeting the TRIM28 and SARS2-NP interaction was screened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication and rescue innate antiviral immunity. Collectively, these data support SARS2-NP SUMOylation is critical for SARS-CoV-2 virulence, and therefore provide a strategy to antagonize SARS-CoV-2.

Abstract Background Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. Methods This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. Discussion APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. Trial registration Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Abstract Despite the stability of the continental interior, eastern North America has hosted many significant historical earthquakes. Seismicity concentrates within tectonically inherited structures, which can act as weak zones where stress accumulates. Within these zones, systematic stress rotations may be explained by long‐wavelength sources. We test the hypothesis that mantle‐flow driven by the Farallon slab contributes to intraplate seismicity via the reactivation of pre‐existing faults. We model the stress field using seismically constrained global high‐resolution finite‐element flow models with CitcomS. To isolate the slab's effect, we vary its buoyancy between a case of neutrality and a case with full negative thermal buoyancy derived from tomography. Low‐viscosity lithospheric weak zones located at failed rifts, loaded by a mass anomaly at depth, transmit elevated stresses to the overlying crust. The sinking of the Farallon slab drives localized mantle flow beneath the central‐eastern US, generating a large stress amplification of 100–150 MPa peaking over the New Madrid Seismic Zone (NMSZ). This stress amplification exerts a continent‐wide clockwise rotation on the stress field, which in the presence of weak zones reproduces some observed deviations of the seismically inferred SHmax from the regional borehole SHmax, bringing optimally oriented faults, closer to failure, some of which are associated with major historical earthquakes, including the Reelfoot Fault in the NMSZ and the Timiskaming Fault in Western Quebec. However, stronger lithospheric viscosity gradients, shallower weak zones, or weaker faults are still needed to fully reproduce the observed stress field in some areas.

Abstract The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single‐mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug‐loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane‐coated nanomaterials offer new opportunities for precise drug delivery and disease‐specific targeting, which represent a versatile platform for targeted therapy in AD.

Head and neck cancer is the main cause of cancer death worldwide, with squamous cell carcinoma (HNSCC) being the second most frequent subtype. HNSCC poses significant health threats due to its high incidence and poor prognosis, underscoring the urgent need for advanced research. Histone modifications play a crucial role in the regulation of gene expression and influencing various biological processes. In the context of HNSCC, aberrant histone modifications are increasingly recognized as critical contributors to its development and pathologic progression. This review demonstrates the molecular mechanisms, by which histone modifications such as acetylation, methylation, phosphorylation, and ubiquitination, impact the pathogenesis of HNSCC. The dysregulation of histone-modifying enzymes, including histone acetyltransferases (HATs), histone deacetylases (HDACs), and histone methyltransferases (HMTs), is discussed for its role in altering chromatin structure and gene expression in HNSCC. Moreover, we will explore the potential of targeting histone modifications as a therapeutic strategy, highlighting current preclinical and clinical studies that investigate histone deacetylase inhibitors (HDIs) and other epigenetic drugs, referring to the completed and ongoing clinical trials on those medications.

BackgroundPolatuzumab vedotin, the first FDA-approved antibody-drug conjugate (ADC) targeting CD79b, is utilized in the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), as well as relapsed or refractory (R/R) DLBCL. Despite its approval, concerns persist regarding the long-term safety profile of polatuzumab vedotin. This study aims to evaluate the adverse events (AEs) associated with polatuzumab vedotin since its approval in 2019, utilizing data mining strategies applied to the FDA Adverse Event Reporting System (FAERS).MethodsSignal detection employed four methodologies, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to evaluate and quantify the signals of polatuzumab vedotin-associated AEs. Additionally, subgroup analyses based on patients age, gender, and fatal cases were conducted to investigate AEs occurrences in specific subpopulations.ResultsA total of 1,521 reports listing polatuzumab vedotin as a “principal suspect (PS)” drug were collected from the FAERS database. Through concurrent compliance with four algorithms, 19 significant Standardized MedDRA Query (SMQ) AEs and 92 significant Preferred Term (PT) AEs were detected. Subgroup analyses revealed a higher incidence of PTs in male patients compared to female patients, increased likelihood of polatuzumab vedotin-associated AEs in elder patients (>65 years), and AEs with a high risk of fatal cases include: blood lactate dehydrogenase increased, cytopenia, and hydronephrosis. The median time to AEs occurrence following polatuzumab vedotin initiation was 18.5 (5∼57.75) days, with 95% of AEs occurred within 162 days.ConclusionThis study identified various AEs associated with polatuzumab vedotin, offering critical insights for clinical monitoring and risk identification in patients receiving polatuzumab vedotin therapy.

BackgroundPostinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear. ObjectiveTo further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs. MethodsWe plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are “randomized controlled trials,” “etomidate,” and “remimazolam.” The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system. ResultsThe protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025. ConclusionsBy synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis. Trial RegistrationPROSPERO CRD42023463120; https://tinyurl.com/333jb8bm International Registered Report Identifier (IRRID)PRR1-10.2196/55948

Atomic-level control of complex oxide heterostructure interfaces has resulted in unprecedented properties and functionalities. The majority of oxide heterointerfaces being intensively investigated maintain lattice coherence and exhibit a flawless epitaxial alignment between the films and the substrates. Here, we report the engineering of a charged incoherent BiFeO3/SrTiO3 interface using a tailored deposition sequence in reactive oxide molecular beam epitaxy. By introducing an additional iron oxide layer to disrupt the lattice coherence at the interface, the overlying BiFeO3 is stabilized in a tetragonal phase with its enhanced ferroelectric polarization pointing toward the SrTiO3 substrate, which drives free electrons to accumulate at the incoherent interface. Our findings reveal how controlling lattice coherence at oxide heterointerfaces can open new avenues for fabricating artificial oxide heterostructures with unique properties through precise interface engineering.

The effectiveness of removing lymph nodes before initial treatment in patients with locally advanced cervical cancer is still debated. This article presents a meta-analysis that systematically evaluates the impact of this approach on oncological outcomes. A systematic literature search of PubMed, Embase, Science Direct, and the Cochrane Database of Systematic Reviews (up to December 2023) was performed to obtain relevant studies. The findings were combined using fixed-effects models to address potential differences. Combined risk ratios (HR) and 95% confidence intervals (CI) were calculated. Egger's test was used to assess publication bias. Out of 1025 screened articles, four studies (involving 838 women) met the inclusion criteria. The results showed that lymph node dissection before initial treatment did not affect overall survival (OS) in patients with locally advanced cervical cancer compared to concurrent radiotherapy (HR = 1.11, 95% CI = 0.91-1.36, P = 0.30). It also did not increase the incidence of postoperative complications or cause delays in radiotherapy. In particular, removing larger lymph nodes (>2cm) aided in defining the radiation field and decreasing radiotherapy-related complications. The surgical technique also had some impact on postoperative complications. In summary, in order to obtain the best therapeutic outcomes, personalized plans should be developed for each patient, accounting for their individual circumstances to achieve precise treatment and enhance their quality of life.

BackgroundPatent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events.MethodsWe analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines.ResultsIn ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics.ConclusionWe identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5’s interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO’s genetic basis, suggesting potential therapeutic targets for future research.

ABSTRACTZur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species. Yersinia pseudotuberculosis is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in Y. pseudotuberculosis. In this study, a comparative transcriptomics analysis between a ∆zur mutant and the wild-type (WT) strain of Y. pseudotuberculosis was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium in vivo. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆zur mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in Y. pseudotuberculosis.IMPORTANCEBacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria. Y. pseudotuberculosis is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur’s regulons was conducted in Y. pseudotuberculosis. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of Y. pseudotuberculosis was emphasized.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery and general anesthesia. The occurrence of POCD seriously affects the postoperative recovery of patients, and leads to prolonged hospital stay, reduced quality of life, increased medical costs, and even higher mortality. There is no definite and effective drug treatment for POCD. More evidence shows that perioperative non-pharmacological intervention can improve postoperative cognitive function and reduce the incidence of POCD. Therefore, our studies summarize the current non-pharmacological interventions of POCD from the aspects of cognitive training, physical activity, transcutaneous electrical acupoint stimulation, noninvasive brain stimulation, non-pharmacological sleep improvement, music therapy, environment, and multimodal combination Interventions, to provide more data for clinical application and research.

BackgroundNerve blocks are widely used in various surgeries to alleviate postoperative pain and promote recovery. However, the impact of nerve block on delirium remains contentious. This study aims to systematically evaluate the influence of Thoracic Paravertebral Nerve Block (TPVB) on the incidence of delirium in patients post Video-Assisted Thoracoscopic Surgery (VATS).MethodsWe conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases in June 2023. The search strategy combined free-text and Medical Subject Headings (MeSH) terms, including perioperative cognitive dysfunction, delirium, postoperative cognitive dysfunction, paravertebral nerve block, thoracic surgery, lung surgery, pulmonary surgery, and esophageal/esophagus surgery. We utilized a random effects model for the analysis and synthesis of effect sizes.ResultsWe included a total of 9 RCTs involving 1,123 participants in our study. In VATS, TPVB significantly reduced the incidence of delirium on postoperative day three (log(OR): −0.62, 95% CI [−1.05, −0.18], p = 0.01, I2 = 0.00%) and postoperative day seven (log(OR): −0.94, 95% CI [−1.39, −0.49], p

AbstractContext Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).Objective To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments.Materials and methods Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.Results HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p

Abstract N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that regulates in various important biological processes. However, its role in human cancer, especially lymph node metastasis, remains largely unknown. Here, we demonstrated N-Acetyltransferase 10 (NAT10), as the only known “writer” of ac4C mRNA modification, was highly expressed in head and neck squamous cell carcinoma (HNSCC) patients with lymph node metastasis. High NAT10 levels in the lymph nodes of patients with HNSCC patients are a predictor of poor overall survival. Moreover, we found that high expression of NAT10 was positively upregulated by Nuclear Respiratory Factor 1 (NRF1) transcription factor. Gain- and loss-of-function experiments displayed that NAT10 promoted cell metastasis in mice. Mechanistically, NAT10 induced ac4C modification of Glycosylated Lysosomal Membrane Protein (GLMP) and stabilized its mRNA, which triggered the activation of the MAPK/ERK signaling pathway. Finally, the NAT10-specific inhibitor, remodelin, could inhibit HNSCC tumorigenesis in a 4-Nitroquinoline 1-oxide (4NQO)-induced murine tumor model and remodel the tumor microenvironment, including angiogenesis, CD8+ T cells and Treg recruitment. These results demonstrate that NAT10 promotes lymph node metastasis in HNSCC via ac4C-dependent stabilization of the GLMP transcript, providing a potential epitranscriptomic-targeted therapeutic strategy for HNSCC.

Abstract To classify early endometrial cancer (EC) on sagittal T2-weighted images (T2WI) by determining the depth of myometrial infiltration (MI) using a computer-aided diagnosis (CAD) method based on a multi-stage deep learning (DL) model. This study retrospectively investigated 154 patients with pathologically proven early EC at the institution between January 1, 2018, and December 31, 2020. Of these patients, 75 were in the International Federation of Gynecology and Obstetrics (FIGO) stage IA and 79 were in FIGO stage IB. An SSD-based detection model and an Attention U-net-based segmentation model were trained to select, crop, and segment magnetic resonance imaging (MRl) images. Then, an ellipse fitting algorithm was used to generate a uterine cavity line (UCL) to obtain MI depth for classification. In the independent test datasets, the uterus and tumor detection model achieves an average precision rate of 98.70% and 87.93%, respectively. Selecting the optimal MRI slices method yields an accuracy of 97.83%. The uterus and tumor segmentation model with mean IOU of 0.738 and 0.655, mean PA of 0.867 and 0.749, and mean DSC of 0.845 and 0.779, respectively. Finally, the CAD method based on the calculated MI depth reaches an accuracy of 86.9%, a sensitivity of 81.8%, and a specificity of 91.7% for early EC classification. In this study, the CAD method implements an end-to-end early EC classification and is found to be on par with radiologists in terms of performance. It is more intuitive and interpretable than previous DL-based CAD methods.