Development of predicting nomograms for diffuse astrocytoma and anaplastic astrocytoma: a study based on the SEER database.

BACKGROUND: Astrocytoma is a type of adult-type diffuse gliomas that includes diffuse astrocytoma (DA) and anaplastic astrocytoma (AA).However, comprehensive investigations into the risk assessment and prognosis of DA and AA using population-based studies remain noticeably scarce. METHODS: In this study, we developed two predictive nomograms to evaluate the susceptibility and prognosis associated with DA and AA. The study cohort comprised 3,837 individuals diagnosed with DA or AA between 2010 and 2019 selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors were identified and used to construct the nomograms for overall death (OD) and cancer-specific death (CSD) rates. The performance of the models was assessed using c-index, calibration curves, and receiver operating characteristic curve (ROC), and the clinical applicability was evaluated using decision curve analysis (DCA). RESULTS: The ROC curves in this study show excellent clinical applicability and predictive power. Notably, the area under the curves (AUCs) of the training and verification queues was higher than 0.80, thereby cementing the models' precision. Additionally, the calibration plots demonstrate that the anticipated mortality rates strikingly match with the measured values.This alignment of figures is sustained in the validation cohort. Furthermore, the decision curve analysis (DCA) corroborates the models' translational potential, reinforcing their relevance within real-world clinical settings. CONCLUSIONS: The presented nomograms have not only exhibited good predictive performance but also showcased pragmatic clinical utility in prognosticating patient outcomes. Significantly, which will undoubtedly serve as a valuable asset for oncologists, facilitating informed treatment decisions and facilitating meticulous follow-up planning.

Broadband Photodetection of Centimeter-Scale T-Phase Gallium Telluride Grown by Molecular Beam Epitaxy.

Two-dimensional (2D) semiconductors have recently attracted considerable attention due to their promising applications in future integrated electronic and optoelectronic devices. Large-scale synthesis of high-quality 2D semiconductors is an increasingly essential requirement for practical applications, such as sensing, imaging, and communications. In this work, homogeneous 2D GaTe films on a centimeter scale are epitaxially grown on fluorphlogopite mica substrates by molecular beam epitaxy (MBE). The epitaxial GaTe thin films showed an atomically 2D layered lattice structure with a T phase, which has not been discovered in the GaTe geometric isomer. Furthermore, semiconducting behavior and high mobility above room temperature were found in T-GaTe epitaxial films, which are essential for application in semiconducting devices. The T-GaTe-based photodetectors demonstrated respectable photodetection performance with a responsivity of 13 mA/W and a fast response speed. By introducing monolayer graphene as the substrate, we successfully realized high-quality GaTe/graphene heterostructures. The performance has been significantly improved, such as the responsivity was enhanced more than 20 times. These results highlight a feasible scheme for exploring the crystal phase of 2D GaTe and realizing the controlled growth of GaTe films on large substrates, which could promote the development of broadband, high-performance, and large-scale photodetection applications.

Targeting the receptor tyrosine kinase MerTK shows therapeutic value in gastric adenocarcinoma.

BACKGROUND: Despite multiple therapeutic modalities, the overall survival of patients with gastric adenocarcinoma remains poor, especially for advanced tumor stages. Although the tyrosine kinase MerTK has shown therapeutic relevance in several tumor entities, its potential effects in gastric adenocarcinoma have not yet been sufficiently characterized. METHODS: MerTK expression and its influence on patient survival were evaluated by immunohistochemistry in a cohort of 140 patients with gastric adenocarcinoma. CRISPR/Cas9 knockout and siRNA knockdown of MerTK in the gastric cancer cell lines SNU1, SNU5, and MKN45 was used to analyze protein expression, growth, migration, and invasion properties in vitro and in a murine xenograft model. MerTK was pharmacologically targeted with the small molecule inhibitor UNC2025 in vitro and in vivo. RESULTS: In patients, high MerTK expression was associated with decreased overall survival (OS) and lymph node metastasis especially in patients without neoadjuvant therapy (p < 0.05). Knockout and knockdown of MerTK reduced cell proliferation and migration both in vitro and in vivo. UNC2025, a small-molecule inhibitor of MerTK, exhibited a significant therapeutic response in vitro and in vivo. Additionally, MerTK expression attenuated the response to neoadjuvant treatment, and its inhibition sensitized tumor cells to 5-Fluorouracil (5-FU)-based chemotherapy in vitro. CONCLUSIONS: Our findings demonstrate the potential value of MerTK as a prognostic biomarker for gastric adenocarcinoma. Targeting MerTK may become a new treatment option, especially for patients with advanced tumors, and may overcome resistance to established chemotherapies.

Severely polarized extracellular acidity around tumour cells.

Extracellular pH impacts many molecular, cellular and physiological processes, and hence is tightly regulated. Yet, in tumours, dysregulated cancer cell metabolism and poor vascular perfusion cause the tumour microenvironment to become acidic. Here by leveraging fluorescent pH nanoprobes with a transistor-like activation profile at a pH of 5.3, we show that, in cancer cells, hydronium ions are excreted into a small extracellular region. Such severely polarized acidity (pH <5.3) is primarily caused by the directional co-export of protons and lactate, as we show for a diverse panel of cancer cell types via the genetic knockout or inhibition of monocarboxylate transporters, and also via nanoprobe activation in multiple tumour models in mice. We also observed that such spot acidification in ex vivo stained snap-frozen human squamous cell carcinoma tissue correlated with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells. Severely spatially polarized tumour acidity could be leveraged for cancer diagnosis and therapy.

Ninjurin 2 Modulates Tumorigenesis, Inflammation, and Metabolism via Pyroptosis.

The nerve injury-induced protein 2 (NINJ2) belongs to a family of homophilic adhesion molecules and was initially found to be involved in nerve regeneration. However, the role of NINJ2 in other cellular processes is not well studied. The Ninj2-deficient mice generated in the current study had a short lifespan and were prone to spontaneous tumors, systemic inflammation, and metabolic defects. Comprehensive carbohydrate and lipid metabolic analyses were performed to better understand the metabolic traits that contribute to these phenotypes. Carbohydrate metabolic analyses showed that NINJ2 deficiency led to defects in monosaccharide metabolism along with accumulation of multiple disaccharides and sugar alcohols. Lipidomic analyses showed that Ninj2 deficiency altered patterns of several lipids, including triglycerides, phospholipids, and ceramides. To identify a cellular process that associated with these metabolic defects, the role of NINJ2 in pyroptosis, a programmed cell death that links cancer, inflammation, and metabolic disorders, was examined. Loss of NINJ2 promoted pyroptosis by activating the NOD-like receptor protein 3 (NLRP3) inflammasome. Taken together, these data reveal a critical role of NINJ2 in tumorigenesis, inflammatory response, and metabolism via pyroptosis.

CHCHD2 up-regulation in Huntington disease mediates a compensatory protective response against oxidative stress.

Huntington disease (HD) is a neurodegenerative disease caused by the abnormal expansion of a polyglutamine tract resulting from a mutation in the HTT gene. Oxidative stress has been identified as a significant contributing factor to the development of HD and other neurodegenerative diseases, and targeting anti-oxidative stress has emerged as a potential therapeutic approach. CHCHD2 is a mitochondria-related protein involved in regulating cell migration, anti-oxidative stress, and anti-apoptosis. Although CHCHD2 is highly expressed in HD cells, its specific role in the pathogenesis of HD remains uncertain. We postulate that the up-regulation of CHCHD2 in HD models represents a compensatory protective response against mitochondrial dysfunction and oxidative stress associated with HD. To investigate this hypothesis, we employed HD mouse striatal cells and human induced pluripotent stem cells (hiPSCs) as models to examine the effects of CHCHD2 overexpression (CHCHD2-OE) or knockdown (CHCHD2-KD) on the HD phenotype. Our findings demonstrate that CHCHD2 is crucial for maintaining cell survival in both HD mouse striatal cells and hiPSCs-derived neurons. Our study demonstrates that CHCHD2 up-regulation in HD serves as a compensatory protective response against oxidative stress, suggesting a potential anti-oxidative strategy for the treatment of HD.

Flexible and Robust Core-Shell PANI/PVDF@PANI Nanofiber Membrane for High-Performance Electromagnetic Interference Shielding.

Developing high-performance electromagnetic interference (EMI) shielding materials that are lightweight and flexible and have excellent mechanical properties is an ideal choice for modern integrated electronic devices and microwave protection. Herein, we report the preparation of core-shell polyaniline (PANI)-based nanofiber membranes for EMI shielding through seed polymerization. Electrospinning a PANI solution leads to homogeneously dispersed PANI on the nanofiber surface, with abundant attachment sites for aniline through electrostatic adsorption and hydrogen bonding interaction, allowing PANI to grow on the nanofiber surfaces. This stable core-shell heterostructure provides more interfaces for reflecting and absorbing microwaves. The PANI/PVDF@PANI membranes achieved a shielding efficiency (SE) of 44.7 dB at a thickness of only 1.2 mm, exhibiting an exceptionally high specific EMI shielding effectiveness (SE/t) of 372.5 dB cm-1. Furthermore, the composite membrane exhibits outstanding mechanical stability, durability, air permeability, and moisture permeability, also making it suitable for applications such as EM shielding clothing.

Ferredoxin 1 is essential for embryonic development and lipid homeostasis.

Mammalian ferredoxin 1 and 2 (FDX1/2) belong to an evolutionary conserved family of iron-sulfur cluster containing proteins and act as electron shutters between ferredoxin reductase (FDXR) and numerous proteins involved in critical biological pathways. FDX1 is involved in biogenesis of steroids and bile acids, Vitamin A/D metabolism, and lipoylation of tricarboxylic acid (TCA) cycle enzymes. FDX1 has been extensively characterized biochemically but its role in physiology and lipid metabolism has not been explored. In this study, we generated Fdx1-deficient mice and showed that knockout of both alleles of the Fdx1 gene led to embryonic lethality. We also showed that like Fdxr+/-+/-, Fdx1+/-+/- had a shorter life span and were prone to steatohepatitis. However, unlike Fdxr+/-+/-, Fdx1+/-+/- were not prone to spontaneous tumors. Additionally, we showed that FDX1 deficiency led to lipid droplet accumulation possibly via the ABCA1-SREBP1/2 pathway. Specifically, untargeted lipidomic analysis showed that FDX1 deficiency led to alterations in several classes of lipids, including cholesterol, triacylglycerides, acylcarnitines, ceramides, phospholipids and lysophospholipids. Taken together, our data indicate that FDX1 is essential for mammalian embryonic development and lipid homeostasis at both cellular and organismal levels.

Clinicopathologic features of relapsed CD19(-) B-ALL in CD19-targeted immunotherapy: Biological insights into relapse and LILRB1 as a novel B-cell marker for CD19(-) B lymphoblasts.

INTRODUCTION: The mechanism of relapsed CD19(-) B-ALL after anti-CD19 immunotherapy (Kymriah [CART-19] and blinatumomab) is under active investigation. Our study aims to assess LILRB1 as a novel B-cell marker for detecting CD19(-) B-lymphoblasts and to analyze the clinicopathologic/genetic features of such disease to provide biological insight into relapse. METHODS: Six patients (3 males/3 females, median age of 14 years) with relapsed CD19(-) B-ALL were analyzed for cytogenetic/genetic profile and immunophenotype. RESULTS: CD19(-) B-ALL emerged after an interval of 5.8 months following anti-CD19 therapy. Five of six patients had B-cell aplasia, indicative of a persistent effect of CART or blinatumomab at relapse. Importantly, LILRB1 was variably expressed on CD19(-) and CD19(+) B lymphoblasts, strong on CD34(+) lymphoblasts and dim/partial on CD34(-) lymphoblasts. Three of six patients with paired B-ALL samples (pre- and post-anti-CD19 therapy) carried complex and different cytogenetic abnormalities, either as completely different or sharing a subset of cytogenetic abnormalities. CONCLUSION: LILRB1 can be used as a novel B-cell marker to identify CD19(-) B lymphoblasts. The emergence of CD19(-) B-ALL appears to be associated with complex cytogenetic evolutions. The mechanism of CD19(-) B-ALL relapse under anti-CD19 immune pressure remains to be explored by comprehensive molecular studies.

Perovskites as oxygen storage materials for chemical looping partial oxidation and reforming of methane.

The traditional partial oxidation, dry reforming and steam reforming of methane technologies are separated into two reactors for execution by chemical looping technology, which can avoid the defects exposed in the traditional process (avoiding carbon accumulation, reducing costs, etc.). The key to chemical looping technology is to find suitable oxygen carriers (OCs), which can store and release oxygen to form a closed loop in the chemical looping. The purpose of this review is to summarize the current status of perovskite oxides for partial oxidation and reforming of methane in chemical looping, describe the structure, oxygen capacity, oxygen migration rate and common synthesis methods of perovskites in chemical looping. In addition, the effects of impregnation loading, ion doping, and structural morphology on the catalytic conversion of CH4 by perovskite OCs and the reaction mechanism on the OCs are also discussed.

Natural and anthropogenic impacts on mercury accumulation in Xiaohai Lagoon, South China over the last 1200 years.

Anthropogenic use and release of mercury (Hg) have profoundly affected the global Hg cycle since preindustrial times. However, it is often difficult to quantify the relative contributions of natural and anthropogenic factors to environmental Hg accumulation. Here, we have presented a 1200-year record of Hg deposition in a sediment core from the Xiaohai Lagoon (South China), in combination with multiple environmental indicators (e.g., geochemical elements, grain size and total organic carbon, etc.). Using principal component analysis (PCA) and stepwise regression analysis (SRA), we aimed to explore the latent processes governing the accumulation of Hg over time and to quantitatively assess the natural and anthropogenic impacts on Hg deposition over the last millennium in Xiaohai Lagoon. Our results have demonstrated that between ∼ 870 and âˆ¼ 1860 CE, natural factors were the main drivers controlling Hg concentrations in the lagoon. These were directly driven by higher soil erosion and increased inputs of fine-grained matter. However, from 1860 to 2013 CE, enhanced anthropogenic activities played a significant role in Hg accumulation in Xiaohai Lagoon. Anthropogenic Hg fluxes increased significantly from ∼ 1860 CE, peaked several times during the 1860s to the 1950s, accelerated from the late 1950s to the early 2000s, and then declined gradually owing to the stringent environmental protection strategies and efficient pollutant control technologies. Our results have suggested that the increased anthropogenic Hg inputs between the 1860s and mid-1970s were mostly attributed to wars, the "Westernization Movement", and global industrial activity, with a surge mainly after the 1980s dominated by industrial activities in China and numerous developing countries in Southeast Asia. This study has shown the natural and anthropogenic influences associated with mercury pollution through quantitative analysis and can deepen our understanding of the processes and mechanisms of mercury deposition in natural environments under the influence of human activities.

Competing Risk Model to Determine the Prognostic Factors for Patients with Gliosarcoma.

BACKGROUND: Gliosarcoma (GSM) is a highly aggressive variant of brain cancer with an extremely unfavorable prognosis. Prognosis is not feasible by traditional methods because of a lack of staging criteria, and the present study aims to screen more detailed demographic factors to predict the prognostic factors of the tumors. METHODS: For this study, we extracted data of patients diagnosed with GSM from the SEER (Surveillance Epidemiology and End Results) database between 2000 and 2019. To account for the influence of competing risks, we used a Cumulative Incidence Function. Subsequently, univariate analysis was conducted to evaluate the individual variables under investigation. Specifically for patients with GSM, we generated cumulative risk curves for specific mortality outcomes and events related to competing risks. In addition, we used both univariate and multivariate Cox analysis to account for non-GSM-related deaths that may confound our research. RESULTS: The competing risk model showed that age, marital status, tumor size, and adjuvant therapy were prognostic factors in GSM-related death. The analysis results showed that older age (60-70 years, ≥71 years) and larger tumor size (≥5.3 cm) significantly increased the risk of GSM-related death. Conversely, surgical intervention, chemotherapy, and being single were identified as protective factors against GSM-related death. CONCLUSIONS: Our study using a competing risk model provided valuable insights into the prognostic factors associated with GSM-related death. Further research and clinical interventions targeted at minimizing these risk factors and promoting the use of protective measures may contribute to improved outcomes and reduced mortality for patients with GSM.

Reconstructing Spatial Transcriptomics at the Single-cell Resolution with BayesDeep.

Spatially resolved transcriptomics (SRT) techniques have revolutionized the characterization of molecular profiles while preserving spatial and morphological context. However, most next-generation sequencing-based SRT techniques are limited to measuring gene expression in a confined array of spots, capturing only a fraction of the spatial domain. Typically, these spots encompass gene expression from a few to hundreds of cells, underscoring a critical need for more detailed, single-cell resolution SRT data to enhance our understanding of biological functions within the tissue context. Addressing this challenge, we introduce BayesDeep, a novel Bayesian hierarchical model that leverages cellular morphological data from histology images, commonly paired with SRT data, to reconstruct SRT data at the single-cell resolution. BayesDeep effectively model count data from SRT studies via a negative binomial regression model. This model incorporates explanatory variables such as cell types and nuclei-shape information for each cell extracted from the paired histology image. A feature selection scheme is integrated to examine the association between the morphological and molecular profiles, thereby improving the model robustness. We applied BayesDeep to two real SRT datasets, successfully demonstrating its capability to reconstruct SRT data at the single-cell resolution. This advancement not only yields new biological insights but also significantly enhances various downstream analyses, such as pseudotime and cell-cell communication.

Application of Polyethylene Glycol-Based Flame-Retardant Phase Change Materials in the Thermal Management of Lithium-Ion Batteries.

Composite phase change materials commonly exhibit drawbacks, such as low thermal conductivity, flammability, and potential leakage. This study focuses on the development of a novel flame-retardant phase change material (RPCM). The material's characteristics and its application in the thermal management of lithium-ion batteries are investigated. Polyethylene glycol (PEG) serves as the medium for phase change; expanded graphite (EG) and multi-walled carbon nanotubes (MWCNT) are incorporated. Moreover, an intumescent flame retardant (IFR) system based on ammonium polyphosphate (APP) is constructed, aided by the inclusion of bio-based flame-retardant chitosan (CS) and barium phytate (PA-Ba), which can improve the flame retardancy of the material. Experimental results demonstrate that the RPCM, containing 15% IFR content, exhibits outstanding flame retardancy, achieving a V-0 flame retardant rating in vertical combustion tests. Moreover, the material exhibits excellent thermomechanical properties and thermal stability. Notably, the material's thermal conductivity is 558% higher than that of pure PEG. After 2C and 3C high-rate discharge cycles, the highest temperature reached by the battery module cooled with RPCM is 18.71 °C lower than that of natural air-cooling; the material significantly reduces the temperature difference within the module by 62.7%, which achieves efficient and safe thermal management.

Unlocking the mysterious polytypic features within vaterite CaCO3.

Calcium carbonate (CaCO3), the most abundant biogenic mineral on earth, plays a crucial role in various fields such as hydrosphere, biosphere, and climate regulation. Of the four polymorphs, calcite, aragonite, vaterite, and amorphous CaCO3, vaterite is the most enigmatic one due to an ongoing debate regarding its structure that has persisted for nearly a century. In this work, based on systematic transmission electron microscopy characterizations, crystallographic analysis and machine learning aided molecular dynamics simulations with ab initio accuracy, we reveal that vaterite can be regarded as a polytypic structure. The basic phase has a monoclinic lattice possessing pseudohexagonal symmetry. Direct imaging and atomic-scale simulations provide evidence that a single grain of vaterite can contain three orientation variants. Additionally, we find that vaterite undergoes a second-order phase transition with a critical point of ~190 K. These atomic scale insights provide a comprehensive understanding of the structure of vaterite and offer advanced perspectives on the biomineralization process of calcium carbonate.

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.

Isoform-specific disruption of the TP73 gene reveals a critical role for TAp73γ in tumorigenesis via leptin.

TP73, a member of the p53 family, is expressed as TAp73 and ΔNp73 along with multiple C-terminal isoforms (α-η). ΔNp73 is primarily expressed in neuronal cells and necessary for neuronal development. Interestingly, while TAp73α is a tumor suppressor and predominantly expressed in normal cells, TAp73 is found to be frequently altered in human cancers, suggesting a role of TAp73 C-terminal isoforms in tumorigenesis. To test this, the TCGA SpliceSeq database was searched and showed that exon 11 (E11) exclusion occurs frequently in several human cancers. We also found that p73α to p73γ isoform switch resulting from E11 skipping occurs frequently in human prostate cancers and dog lymphomas. To determine whether p73α to p73γ isoform switch plays a role in tumorigenesis, CRISPR technology was used to generate multiple cancer cell lines and a mouse model in that Trp73 E11 is deleted. Surprisingly, we found that in E11-deificient cells, p73γ becomes the predominant isoform and exerts oncogenic activities by promoting cell proliferation and migration. In line with this, E11-deficient mice were more prone to obesity and B-cell lymphomas, indicating a unique role of p73γ in lipid metabolism and tumorigenesis. Additionally, we found that E11-deficient mice phenocopies Trp73-deficient mice with short lifespan, infertility, and chronic inflammation. Mechanistically, we showed that Leptin, a pleiotropic adipocytokine involved in energy metabolism and oncogenesis, was highly induced by p73γ,necessary for p73γ-mediated oncogenic activity, and associated with p73α to γ isoform switch in human prostate cancer and dog lymphoma. Finally, we showed that E11-knockout promoted, whereas knockdown of p73γ or Leptin suppressed, xenograft growth in mice. Our study indicates that the p73γ-Leptin pathway promotes tumorigenesis and alters lipid metabolism, which may be targeted for cancer management.

Clinical Features and Risk Stratification of Multiple Myeloma Patients with COVID-19.

SARS-CoV-2 infection often results in a more severe COVID-19 disease course in multiple myeloma (MM) patients compared to immunocompetent individuals. The aim of this report is to summarize the clinical features of the MM patients with COVID-19 and the impact of MM treatment on outcomes to guide risk stratification and ensure the appropriate management of the patients. Serological responses in MM patients post-infection or -vaccination are also reviewed to better understand the strategy of prevention. Along with reports from the literature, we presented findings from a retrospective analysis of the clinical characteristics and outcomes of COVID-19 infection in MM patients in our institution. Study population includes 34 MM patients with a median age of 61 (range: 35-82 years) who tested positive for SARS-CoV-2 between 1 March 2020-15 August 2021. We examined the effect of chemotherapy, the benefit of neutralizing monoclonal antibody (Bamlanivimab) and the impact of anti-CD38 antibody (daratumumab) on the hospitalization and mortality of the patients, as well as the efficacy of native antibody production. Our results showed that MM patients have increased hospitalization and mortality rates from COVID-19 compared with that of general population, especially those on active chemotherapy. Advanced age, high-risk myeloma, renal disease, and suboptimal disease control are independent predictors of adverse outcomes. The use of daratumumab does not increase the disease severity/hospitalization or the post-infection/vaccination seropositivity of SARS-CoV-2. The neutralizing antibody decreases overall mortality. Evidence from the current study and previous publications suggest that testing of neutralizing antibody post-SARS-CoV-2 vaccination in MM patients may be needed in reducing COVID-19 risk.

The Synthesis and Polymer-Reinforced Mechanical Properties of SiO2 Aerogels: A Review.

Silica aerogels are considered as the distinguished materials of the future due to their extremely low thermal conductivity, low density, and high surface area. They are widely used in construction engineering, aeronautical domains, environmental protection, heat storage, etc. However, their fragile mechanical properties are the bottleneck restricting the engineering application of silica aerogels. This review briefly introduces the synthesis of silica aerogels, including the processes of sol-gel chemistry, aging, and drying. The effects of different silicon sources on the mechanical properties of silica aerogels are summarized. Moreover, the reaction mechanism of the three stages is also described. Then, five types of polymers that are commonly used to enhance the mechanical properties of silica aerogels are listed, and the current research progress is introduced. Finally, the outlook and prospects of the silica aerogels are proposed, and this paper further summarizes the methods of different polymers to enhance silica aerogels.

SLF2 Interacts with the SMC5/6 Complex to Direct Hepatitis B Virus Episomal DNA to Promyelocytic Leukemia Bodies for Transcriptional Repression.

Hepatitis B virus (HBV) chronically infects approximately 300 million people worldwide, and permanently repressing transcription of covalently closed circular DNA (cccDNA), the episomal viral DNA reservoir, is an attractive approach toward curing HBV. However, the mechanism underlying cccDNA transcription is only partially understood. In this study, by illuminating cccDNA of wild-type HBV (HBV-WT) and transcriptionally inactive HBV that bears a deficient HBV X gene (HBV-ΔX), we found that the HBV-ΔX cccDNA more frequently colocalizes with promyelocytic leukemia (PML) bodies than that of HBV-WT cccDNA. A small interfering RNA (siRNA) screen targeting 91 PML body-related proteins identified SMC5-SMC6 localization factor 2 (SLF2) as a host restriction factor of cccDNA transcription, and subsequent studies showed that SLF2 mediates HBV cccDNA entrapment in PML bodies by interacting with the SMC5/6 complex. We further showed that the region of SLF2 comprising residues 590 to 710 interacts with and recruits the SMC5/6 complex to PML bodies, and the C-terminal domain of SLF2 containing this region is necessary for repression of cccDNA transcription. Our findings shed new light on cellular mechanisms that inhibit HBV infection and lend further support for targeting the HBx pathway to repress HBV activity. IMPORTANCE Chronic HBV infection remains a major public health problem worldwide. Current antiviral treatments rarely cure the infection, as they cannot clear the viral reservoir, cccDNA, in the nucleus. Therefore, permanently silencing HBV cccDNA transcription represents a promising approach for a cure of HBV infection. Our study provides new insights into the cellular mechanisms that restrict HBV infection, revealing the role of SLF2 in directing HBV cccDNA to PML bodies for transcriptional repression. These findings have important implications for the development of antiviral therapies against HBV.