Molecular Engineering to Regulate the Pseudo-Graphitic Structure of Hard Carbon for Superior Sodium Energy Storage.

Resin-derived hard carbons have shown great advantages in serving as promising anode materials for sodium-ion batteries due to their flexible microstructure tunability. However, it remains a daunting challenge to rationally regulate the pseudo-graphitic crystallite and defect of hard carbon toward advanced sodium storage performance. Herein, a molecular engineering strategy is demonstrated to modulate the cross-linking degree of phenolic resin and thus optimize the microstructure of hard carbon. Remarkably, the resorcinol endows resin with a moderate cross-linking degree, which can finely tune the pseudo-graphitic structure with enlarged interlayer spacing and restricted surface defects. As a consequence, the optimal hard carbon delivers a notable reversible capacity of 334.3 mAh g-1 at 0.02 A g-1, a high initial Coulombic efficiency of 82.1%, superior rate performance of 103.7 mAh g-1 at 2 A g-1, and excellent cycling durability over 5000 cycles. Furthermore, kinetic analysis and in situ Raman spectroscopy are performed to reveal the electrochemical advantage and sodium storage mechanism. This study fundamentally sheds light on the molecular design of resin-based hard carbons to advance sodium energy for scale-up applications.

High value-added utilization of desulfurized building gypsum as self-leveling mortar: the comprehensive effect of cement.

The utilization of desulfurized building gypsum as raw material for gypsum-based self-leveling mortar (GSL) is limited by its low strength and poor water resistance. The objective of this study is to enhance comprehensive properties of GSL and prepare qualified desulfurized building gypsum-based self-leveling mortar that can be effectively applied in practical engineering projects. The influence of cement on water consumption rate of initial fluidity (W/M ratio), fluidity, setting time, mechanical strength, and water resistance of GSL were evaluated. Additionally, rheological parameter, heat of hydration, crystal morphology, and pore structure were also analyzed. Cement significantly improved the fluidity of slurry. Moreover, the compressive strength and softening coefficient of GSL reached 20.6 MPa and 0.56 at 10% cement, respectively. Furthermore, cement reduced the 30-min-fluidity loss and improved fludity by reducing the yield stress and increasing the plastic viscosity of screed. The transformation of hydration kinetics of GSL could be due to Ca2+ and OH- released by cement, thus resulting in the shortening of initial setting time and the prolongation of the interval between initial and final setting time. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) showed that CSH gel and AFt crystal would generate on the surface of CaSO4·2H2O crystal, making the structure more compact. Mercury intrusion porosimetry (MIP) indicated that cement greatly reduced the porosity through the water reduction effect in the early stage and continuous hydration in the later stage. The continuous hydration of cement also increased the shrinkage rate. This work was expected to provide reference for promoting the application of desulfurized building gypsum as the high value-added screed.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Heterovalent Metal Pair Sites on Metal-Organic Framework Ordered Macropores for Multimolecular Co-Activation.

The precise design of catalytic metal centers with multiple chemical states to facilitate sophisticated reactions involving multimolecular activation is highly desirable but challenging. Herein, we report an ordered macroporous catalyst with heterovalent metal pair (HMP) sites comprising CuII-CuI on the basis of a microporous metal-organic framework (MOF) system. This macroporous HMP catalyst with proximity heterovalent dual copper sites, whose distance is controlled to ∼2.6 Å, on macropore surface exhibits a co-activation behavior of ethanol at CuII and alkyne at CuI, and avoids microporous restriction, thereby promoting additive-free alkyne hydroboration reaction. The desired yield enhances dramatically compared with the pristine MOF and ordered macroporous MOF both with solely isovalent CuII-CuII sites. Density functional theory calculations reveal that the Cu-HMP sites can stabilize the Bpin-CuII-CuI-alkyne intermediate and facilitate C-B bond formation, resulting in a smooth alkyne hydroboration process. This work provides new perspectives to design multimolecular activation catalysts for sophisticated matter transformations.

Path integration method for stochastic responses of differential equations under Lévy white noise.

A path integration (PI) approach that is progressive for studying the stochastic response driven by Lévy white noise is presented. First, a probability mapping is constructed, which decouples the domain of interest for the system state and the probability space derived from the randomness of Lévy white noise within a short time interval. Then, solving the probability mapping yields the short-time response of the system. Finally, the stochastic evolution of the system can be grasped in a stepwise manner based on the fundamental concept of the PI method. The applicability and effectiveness of our approach in addressing the transient and stationary responses under Lévy white noises are verified by Monte Carlo simulation results. Moreover, the advances in utilization of this method are that it eliminates the restriction of the previous PI method on the controlling parameter of Lévy white noises, and it is highly efficient for solving responses of systems under Lévy white noises.

Manipulating the Host-Guest Chemistry of Cucurbituril to Propel Highly Reversible Zinc Metal Anodes.

Rechargeable aqueous zinc-ion batteries are practically plagued by the short lifespan and low Coulombic efficiency (CE) of Zn anodes resulting from random dendrite deposition and parasitic reactions. Herein, the host-guest chemistry of cucurbituril additive with Zn2+ to achieve longstanding Zn anodes is manipulated. The macrocyclic molecule of cucurbit[5]uril (CB[5]) is delicately designed to reconstruct both the CB[5]-adsorbed electric-double layer (EDL) structure at the Zn interface and the hydrated sheath of Zn2+ ions. Especially benefiting from the desirable carbonyl rims and suitable hydrophobic cavities, the CB[5] has a strong host-guest interaction with Zn2+ ions, which exclusively permits rapid Zn2+ flux across the EDL interface but retards the H2O radicals and SO4 2-. Accordingly, such a unique particle redistributor warrants long-lasting dendrite-free deposition by homogenizing Zn nucleation/growth and significantly improved CE by inhibiting side reactions. The Zn anode can deliver superior reversibility in CB[5]-containing electrolyte with a ninefold increase of cycle lifetime and an elevated CE of 99.7% under harsh test conditions (10 mA cm-2/10 mA h cm-2). The work opens a new avenue from the perspective of host-guest chemistry to propel the development of rechargeable Zn metal batteries and beyond.

Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.

Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status. Using Cabernet, we revealed the 5mC, hemi-5mC and 5hmC dynamics during early mouse embryo development, uncovering genomic regions exclusively governed by active or passive demethylation. We show that hemi-methylation status can be used to distinguish between pre- and post-replication cells, enabling more efficient cell grouping when integrated with 5mC profiles. The property of Tn5 naturally enables Cabernet to achieve high-throughput single-cell methylome profiling, where we probed mouse cortical neurons and embryonic day 7.5 (E7.5) embryos, and constructed the library for thousands of single cells at high efficiency, demonstrating its potential for analyzing complex tissues at substantially low cost. Together, we present a way of high-throughput methylome and hydroxymethylome detection at single-cell resolution, enabling efficient analysis of the epigenetic status of biological systems with complicated nature such as neurons and cancer cells.

Recent Advances and Future Prospects of Mycosporine-like Amino Acids.

Mycosporine-like amino acids (MAAs) are a class of water-soluble active substances produced by various aquatic organisms. However, due to the limitations of low accumulation of MAAs in organisms, the cumbersome extraction process, difficult identification, and high cost, MAAs have not yet been widely used in human life. Recently, there has been an emergence of heterologous synthesis for MAAs, making increasing yield the key to the quantification and application of MAAs. This review summarizes the latest research progress of MAAs, including: (1) introducing the biodistribution of MAAs and the content differences among different species to provide a reference for the selection of research subjects; (2) elaborating the species and molecular information of MAAs; (3) dissecting the synthesis mechanism and sorting out the synthesis pathways of various MAAs; (4) summarizing the methods of extraction and identification, summarizing the advantages and disadvantages, and providing a reference for the optimization of extraction protocols; (5) examining the heterologous synthesis method; and (6) summarizing the physiological functions of MAAs. This paper comprehensively updates the latest research status of MAAs and the various problems that need to be addressed, especially emphasizing the potential advantages of heterologous synthesis in the future production of MAAs.

Kidney Involvement in Autoinflammatory Diseases.

Background: Autoinflammatory diseases (AIDs) were first proposed 20 years ago and caused by dysregulation of the innate immune system, leading to episodes of systemic inflammation. Advances in next-generation sequencing and biological technology have resulted in the identification of new monogenic diseases and the corresponding signaling pathways that may guide us in targeted therapy. The kidney is a major target organ of various inflammatory processes. Summary: During systemic inflammation, increased pro-inflammatory cytokines, such as IL-6, IL-1ß, and TNF, lead to over-transcription and release of acute phase reactant serum amyloid A (SAA). Sustained high SAA levels promote a cascade of pathophysiological events, including protein misfolding, protein fragmentation, and aggregation into highly ordered amyloid fibrils. Amyloid fibril deposition in the kidney cause progressive glomerular and vascular damage. Renal AA amyloidosis is a common and severe complication of AIDs, including familial Mediterranean fever, cryopyrin-associated periodic syndromes, TNF receptor-associated periodic fever syndrome, mevalonate kinase deficiency/hyper-IgD and periodic fever syndrome, and deficiency of adenosine deaminase 2. Amyloidosis may even be the first clinical manifestation in some patients, presenting with asymptomatic proteinuria, nephritic syndrome, progressive renal insufficiency, or end-stage kidney disease. In addition, major dysregulated pathways in different AIDs lead to endogenous inflammation, which is due to direct endothelial cytotoxicity caused by IL-1ß, type I interferon, or possibly immune complexes. The kidney is frequently affected by various vasculitis, and kidney involvement is a major determinant of treatment options and outcomes. The renal vasculitis involved in AIDs includes renal artery Takayasu vasculitis, polyarteritis nodosa, and IgA vasculitis. Moreover, other kidney diseases, such as glomerulonephritis, lupus nephritis, and renal tubular dysfunction, were also reported in AIDs. Key Messages: Kidney manifestations can be a coexisting disease seen with AIDs. They may also be one of the characteristics of AIDs. Clinicians should be aware of the possibility that amyloidosis, vasculitis, or other kidney diseases may be associated with AIDs in order to make appropriate diagnosis and treatment. Kidney biopsy may be of great significance. Biologics, which switch off the underlying cytokine-mediated inflammatory process, have the potential to restore organ damage and improve the outcome in the very early stage of the disease.

The identification of piecewise non-linear dynamical system without understanding the mechanism.

This paper designs an algorithm to distill the piecewise non-linear dynamical system from the data without prior knowledge. The system to be identified does not have to be written as a known model term or be thoroughly understood. We exploit the fact that an unknown piecewise non-linear system can be decomposed into the Fourier series as long as its equations of motion are Riemann integrable. Based on this property, we reduce the challenge of finding the correct model to discovering the Fourier series approximation. However, the Fourier series approximation of the piecewise function is inaccurate. The new method takes advantage of this weakness to determine whether the model has piecewise features and to find a way to discover the discontinuity set. Then, the dynamical system on each segment is identified as a pure Fourier series. Identification of intricate models can be achieved in simple steps. The results show that the method can accurately discover the equation of motion and precisely capture the non-smooth characteristic. Next, the prediction and further detailed analysis can be carried out.

Genome-Wide Identification and Expression Analysis of Dendrocalamus farinosus CCoAOMT Gene Family and the Role of DfCCoAOMT14 Involved in Lignin Synthesis.

As the main component of plant cell walls, lignin can not only provide mechanical strength and physical defense for plants, but can also be an important indicator affecting the properties and quality of wood and bamboo. Dendrocalamus farinosus is an important economic bamboo species for both shoots and timber in southwest China, with the advantages of fast growth, high yield and slender fiber. Caffeoyl-coenzyme A-O-methyltransferase (CCoAOMT) is a key rate-limiting enzyme in the lignin biosynthesis pathway, but little is known about it in D. farinosus. Here, a total of 17 DfCCoAOMT genes were identified based on the D. farinosus whole genome. DfCCoAOMT1/14/15/16 were homologs of AtCCoAOMT1. DfCCoAOMT6/9/14/15/16 were highly expressed in stems of D. farinosus; this is consistent with the trend of lignin accumulation during bamboo shoot elongation, especially DfCCoAOMT14. The analysis of promoter cis-acting elements suggested that DfCCoAOMTs might be important for photosynthesis, ABA/MeJA responses, drought stress and lignin synthesis. We then confirmed that the expression levels of DfCCoAOMT2/5/6/8/9/14/15 were regulated by ABA/MeJA signaling. In addition, overexpression of DfCCoAOMT14 in transgenic plants significantly increased the lignin content, xylem thickness and drought resistance of plants. Our findings revealed that DfCCoAOMT14 can be a candidate gene that is involved in the drought response and lignin synthesis pathway in plants, which could contribute to the genetic improvement of many important traits in D. farinosus and other species.

Pathogenic Gene Spectrum and Clinical Implication in Chinese Patients with Lupus Nephritis.

BACKGROUND: Lupus nephritis is a rare immunological disorder. Genetic factors are considered important in its causation. We aim to systematically investigate the rare pathogenic gene variants in patients with lupus nephritis. METHODS: Whole-exome sequencing was used to screen pathogenic gene variants in 1886 probands with lupus nephritis. Variants were interpreted on the basis of known pathogenic variants or the American College of Medical Genetics and Genomics guidelines and studied by functional analysis, including RNA sequencing, quantitative PCR, cytometric bead array, and Western blotting. RESULTS: Mendelian form of lupus nephritis was confirmed in 71 probands, involving 63 variants in 39 pathogenic genes. The detection yield was 4%. The pathogenic genes enriched in nuclear factor kappa-B (NF-κB), type I interferon, phosphatidylinositol-3-kinase/serine/threonine kinase Akt (PI3K/AKT), Ras GTPase/mitogen-activated protein kinase (RAS/MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Clinical manifestation patterns were diverse among different signaling pathways. More than 50% of the pathogenic gene variants were reported to be associated with lupus or lupus nephritis for the first time. The identified pathogenic gene variants of lupus nephritis overlapped with those of autoinflammatory and immunodeficiency diseases. Inflammatory signatures, such as cytokine levels of IL-6, IL-8, IL-1 ß , IFN α , IFN γ , and IP10 in serum and transcriptional levels of interferon-stimulated genes in blood, were significantly higher in patients with pathogenic gene variants compared with controls. The overall survival rate of patients with pathogenic gene variants was lower than those without pathogenic gene variants. CONCLUSIONS: A small fraction of patients with lupus nephritis had identifiable pathogenic gene variants, primarily in NF-κB, type I interferon, PI3K/AKT, JAK/STAT, RAS/MAPK, and complement pathways.

Quantification of dissipative effects in a complex Ginzburg-Landau equation governed laser system by tracing soliton dynamics.

The concept of dissipative solitons has provided new insight into the complex pulse dynamics in mode-locked lasers and stimulated novel laser cavity designs. However, most of these studies are restricted to qualitative regimes, because it is difficult to quantify dissipative effects in a mode-locked laser. Meanwhile, the quantification of dissipative effects is a general problem that can be also encountered in other dissipative systems. In this paper, we demonstrate a method for quantifying dissipative effects in a mode-locked laser based on analyzing the soliton dynamics traced by time-stretch dispersive Fourier transform. As a result, we are able to quantitatively reproduce the evolution of the pulse that seeds mode-locking through simulations and gain a deeper understanding of the whole process. The obtained physical picture of mode-locking allows us to propose a simple method to quantify the energy threshold for mode-locking buildup and the stability of mode-locked states. A parameter is introduced to evaluate mode-locking conditions, which can serve as a criterion for designing mode-locked lasers. This work opens up new possibilities in the diagnosis and improvement of mode-locked lasers and studies of soliton physics.

Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation.

BACKGROUND: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus, with heterogeneous phenotypes and different responses to therapy. Identifying genetic causes of LN can facilitate more individual treatment strategies. METHODS: We performed whole-exome sequencing in a cohort of Chinese patients with LN and identified variants of a disease-causing gene. Extensive biochemical, immunologic, and functional analyses assessed the effect of the variant on type I IFN signaling. We further investigated the effectiveness of targeted therapy using single-cell RNA sequencing. RESULTS: We identified a novel DDX58 pathogenic variant, R109C, in five unrelated families with LN. The DDX58 R109C variant is a gain-of-function mutation, elevating type I IFN signaling due to reduced autoinhibition, which leads to RIG-I hyperactivation, increased RIG-I K63 ubiquitination, and MAVS aggregation. Transcriptome analysis revealed an increased IFN signature in patient monocytes. Initiation of JAK inhibitor therapy (baricitinib 2 mg/d) effectively suppressed the IFN signal in one patient. CONCLUSIONS: A novel DDX58 R109C variant that can cause LN connects IFNopathy and LN, suggesting targeted therapy on the basis of pathogenicity. PODCAST: This article contains a podcast at.

Novel loss-of-function mutations in TNFAIP3 gene in patients with lupus nephritis.

Background: Heterozygous loss-of-function mutations in the tumour necrosis factor alpha induced protein 3 (TNFAIP3) gene cause an early-onset auto-inflammatory disease named haploinsufficiency of A20 (HA20). Here we describe three unrelated patients with autoimmune lupus nephritis (LN) phenotypes carrying three novel mutations in the TNFAIP3 gene. Methods: Whole-exome sequencing (WES) was used to identify the causative mutations in three biopsy-proven LN patients. Sanger sequencing and quantitative polymerase chain reaction (qPCR) were used to validate the mutations identified by WES. RNA sequencing, qPCR and cytometric bead array was used to detect inflammatory signatures in the patients. Results: The patients predominantly presented with an autoimmune phenotype, including autoimmune haemolytic anaemia, multipositive autoantibodies and LN. Additionally, novel phenotypes of allergy and pericardial effusion were first reported. WES identified three novel heterozygous mutations in the TNFAIP3 gene, including a novel splicing mutation located in the canonical splicing site (c.634+2T>C) resulting in an intron 4 insertion containing a premature stop codon, a de novo novel copy number variation (exon 7-8 deletion) and a novel nonsense mutation c.1300_1301delinsTA causing a premature stop codon. We further identified hyperactivation signatures of nuclear factor- kappa B and type I IFN signalling and overproduction of pro-inflammatory cytokines in the blood. This report expanded the phenotype to a later age, as two girls were diagnosed at age 3 years and one man at age 29 years. Conclusions: Kidney involvement may be the main feature of the clinical spectrum of HA20, even in adults. Genetic screening should be considered for early-onset LN patients.

Simple and cost-effective broad bandwidth fiber chirped pulse amplification laser system seeded by a nonlinear amplifier.

In this paper, we demonstrate a simple and cost-effective fiber chirped pulse amplification (CPA) laser system, where a nonlinear amplifier is employed to generate broadband seeding pulses. The nonlinear amplifier can generate stable pulses with 50 nm spectral bandwidth and linear chirp. With such a seeding configuration being adapted into a fiber CPA laser system, the output bandwidth can be expanded from 7 nm to 20 nm, with only minor changes to a standard industrial fiber CPA system. The increased bandwidth allows for pulse durations of less than 100 fs, which is significantly shorter than the original configuration's 250 fs. When combined with a Fourier pulse shaper, such a fiber laser system is expected to produce pulses with energy exceeding 100 µJ and duration shorter than 100 fs.

Decreased Serum Dickkopf-1 Levels After Hypoglycemic Therapy in Patients with Type 2 Diabetes Mellitus.

Aim: Dickkopf-1 (DKK-1) is a major inhibitor of Wingless protein signaling pathway, which is involved in glucose metabolism and cardiovascular diseases. The aim of the study was to investigate the changes of serum DKK-1 levels after hypoglycemic treatments and the relationship between DKK-1 and clinical parameters. Materials and Methods: The study was a sub-study of a previously published clinical trial (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed insulin compared to metformin). All subjects underwent anthropometric and biochemical assessments at baseline and endpoint. Serum DKK-1 levels of 92 subjects were measured at baseline and after 12-week hypoglycemic treatment. Results: DKK-1 levels were significantly decreased after hypoglycemic treatment for 12 weeks (P < 0.001). ΔDKK-1 levels were not correlated with improvement of metabolic parameters (all P > 0.05) but were negatively correlated with baseline DKK-1 levels (r = -0.263, P = 0.011). Spearman correlation showed that baseline DKK-1 levels were positively related to baseline total cholesterol (r = 0.226, P = 0.030) and low-density lipoprotein cholesterol (LDL-C) (r = 0.277, P = 0.007). Compared with the higher baseline DKK-1 group (≥3700 pg/mL), subjects in the lower baseline DKK-1 group (<3700 pg/mL) had significantly lower baseline glycated hemoglobin A1c levels (P = 0.008) and LDL-C levels (P = 0.048). Systolic and diastolic pressure were decreased more significantly in the lower baseline DKK-1 group than that in the higher baseline DKK-1 group (both P < 0.05). Conclusion: Serum DKK-1 levels were decreased after hypoglycemic treatments. Patients with lower baseline DKK-1 levels were featured by more favorable cardiometabolic factors.

Integrated analysis of inflammatory response subtype-related signature to predict clinical outcomes, immune status and drug targets in lower-grade glioma.

Background: The inflammatory response in the tumor immune microenvironment has implications for the progression and prognosis in glioma. However, few inflammatory response-related biomarkers for lower-grade glioma (LGG) prognosis and immune infiltration have been identified. We aimed to construct and identify the prognostic value of an inflammatory response-related signature, immune infiltration, and drug targets for LGG. Methods: The transcriptomic and clinical data of LGG samples and 200 inflammatory response genes were obtained from public databases. The LGG samples were separated into two inflammatory response-related subtypes based on differentially expressed inflammatory response genes between LGG and normal brain tissue. Next, inflammatory response-related genes (IRRGs) were determined through a difference analysis between the aforementioned two subtypes. An inflammatory response-related prognostic model was constructed using IRRGs by using univariate Cox regression and Lasso regression analyses and validated in an external database (CGGA database). ssGSEA and ESTIMATE algorithms were conducted to evaluate immune infiltration. Additionally, we performed integrated analyses to investigate the correlation between the prognostic signature and N 6-methyladenosine mRNA status, stemness index, and drug sensitivity. We finally selected MSR1 from the prognostic signature for further experimental validation. Results: A total of nine IRRGs were identified to construct the prognostic signature for LGG. LGG patients in the high-risk group presented significantly reduced overall survival than those in the low-risk group. An ROC analysis confirmed the predictive power of the prognostic model. Multivariate analyses identified the risk score as an independent predictor for the overall survival. ssGSEA revealed that the immune status was definitely disparate between two risk subgroups, and immune checkpoints such as PD-1, PD-L1, and CTLA4 were significantly expressed higher in the high-risk group. The risk score was strongly correlated with tumor stemness and m6A. The expression levels of the genes in the signature were significantly associated with the sensitivity of tumor cells to anti-tumor drugs. Finally, the knockdown of MSR1 suppressed LGG cell migration, invasion, epithelial-mesenchymal transition, and proliferation. Conclusion: The study constructed a novel signature composed of nine IRRGs to predict the prognosis, potential drug targets, and impact immune infiltration status in LGG, which hold promise for screening prognostic biomarkers and guiding immunotherapy for LGG.

Epithelial-Myoepithelial Carcinoma of the Esophagus: A Case Report.

Epithelial-myoepithelial carcinoma (EMC) of the esophagus is a rare biphasic tumor with low malignant potential, which has not previously been reported in the published literature. The present study describes the case of an asymptomatic, 53-year-old male who presented with EMC in the esophagus during a gastroscopic examination. Esophageal computed tomography (CT) showed thickening of the wall of the lower esophagus with a thickness of about 0.7 cm, and an enhanced scan showed uneven enhancement of the thickened esophageal wall. Thoracoscopic esophagectomy was performed because the tumor was malignant. Histopathology revealed that the tumor was characterized by a biphasic architecture consisting of cuboidal ductal cells and myoepithelial cells. The patient's postoperative recovery was eventful, an anastomotic fistula occurred, and the patient was discharged from the hospital after 84 days. One year postsurgery, the patient remained in good health, with no evidence of metastasis and recurrence.

Biomimetic Redox-Responsive Mesoporous Organosilica Nanoparticles Enhance Cisplatin-Based Chemotherapy.

Cisplatin-based chemotherapy is dominated in several cancers; however, insufficient therapeutic outcomes and systemic toxicity hamper their clinical applications. Controlled release of cisplatin and reducing inactivation remains an urgent challenge to overcome. Herein, diselenide-bridged mesoporous organosilica nanoparticles (MON) coated with biomimetic cancer cell membrane were tailored for coordination responsive controlled cisplatin delivery and GSH depletion to strengthen Pt-based chemotherapy. Cisplatin-loaded MON (MON-Pt) showed high loading capacity due to robust coordination between selenium and platinum atoms and preventing premature leakage in normal tissue. MON-Pt exhibited a controlled release of activated cisplatin in response to the redox tumor microenvironment. Meanwhile, MON-Pt containing redox-responsive diselenide bonds could efficiently scavenge intracellular inactivation agents, such as GSH, to enhance Pt-based chemotherapy. 4T1 breast cancer cell membranes cloaked MON-Pt (MON-Pt@CM) performed efficient anticancer performance and low in vivo system toxicity due to long blood circulation time and high tumor accumulation benefiting from the tumor targeting and immune-invasion properties of the homologic cancer cell membrane. These results suggest a biomimetic nanocarrier to control release and reduce the inactivation of cisplatin for efficient and safe Pt-based chemotherapy by responding and regulating the tumor microenvironment.