Deciphering a reliable synergistic bispecific strategy of rescuing antibodies for SARS-CoV-2 escape variants, including BA.2.86, EG.5.1, and JN.1.

The game between therapeutic monoclonal antibodies (mAbs) and continuously emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has favored the virus, as most therapeutic mAbs have been evaded. Addressing this challenge, we systematically explored a reproducible bispecific antibody (bsAb)-dependent synergistic effect in this study. It could effectively restore the neutralizing activity of the bsAb when any of its single mAbs is escaped by variants. This synergy is primarily attributed to the binding angle of receptor-binding domain (RBD)-5, facilitating inter-spike cross-linking and promoting cryptic epitope exposure that classical antibody cocktails cannot achieve. Furthermore, RBD-5 with RBD-2, RBD-6, and RBD-7, alongside RBD-8, also exhibit significantly enhanced effects. This study not only shifts the paradigm in understanding antibody interactions but paves the way for developing more effective therapeutic antibodies against rapidly mutating SARS-CoV-2, with Dia-19 already showing promise against emerging variants like BA.2.86, EG.5.1, and JN.1.

Urban airborne PM2.5 induces pulmonary fibrosis through triggering glycolysis and subsequent modification of histone lactylation in macrophages.

Airborne fine particulate matter (PM2.5) can cause pulmonary inflammation and even fibrosis, however, the underlying molecular mechanisms of the pathogenesis of PM2.5 exposure have not been fully appreciated. In the present study, we explored the dynamics of glycolysis and modification of histone lactylation in macrophages induced by PM2.5-exposure in both in vivo and in vitro models. Male C57BL/6 J mice were anesthetized and administrated with PM2.5 by intratracheal instillation once every other day for 4 weeks. Mouse RAW264.7 macrophages and alveolar epithelial MLE-12 cells were treated with PM2.5 for 24 h. We found that PM2.5 significantly increased lactate dehydrogenase (LDH) activities and lactate contents, and up-regulated the mRNA expression of key glycolytic enzymes in the lungs and bronchoalveolar lavage fluids of mice. Moreover, PM2.5 increased the levels of histone lactylation in both PM2.5-exposed lungs and RAW264.7 cells. The pro-fibrotic cytokines secreted from PM2.5-treated RAW264.7 cells triggered epithelial-mesenchymal transition (EMT) in MLE-12 cells through activating transforming growth factor-ß (TGF-ß)/Smad2/3 and VEGFA/ERK pathways. In contrast, LDHA inhibitor (GNE-140) pretreatment effectively alleviated PM2.5-induced pulmonary inflammation and fibrosis via inhibiting glycolysis and subsequent modification of histone lactylation in mice. Thus, our findings suggest that PM2.5-induced glycolysis and subsequent modification of histone lactylation play critical role in the PM2.5-associated pulmonary fibrosis.

Research trends and hotspots of exercise for people with sarcopenic: A bibliometric analysis.

This study aimed to analyze the trends and themes in exercise and sarcopenia research using a bibliometric approach. The Web of Science citation database was used to identify papers published on exercise and sarcopenia. The retrieved data on institutions, journals, countries, authors, journal distribution, and keywords were analyzed scientometric ally using CiteSpace and VOSviewer. 2895 papers were included according to our specified inclusion criteria eventually. The data showed an upward trend in the number of published articles on exercise and sarcopenia. The countries with the highest number of publications were the United States, Japan, and England; research institutions were mainly composed of universities in Europe and the United States, and high-producing authors formed major collaborative teams, but cross-geographical and cross-institutional collaboration was not apparent; research was closely focused on 3 aspects: resistance exercise, resistance combined with other forms of exercise, and exercise combined with nutritional supplementation, of which resistance exercise was a particular focus; and recently, the research hotspots were mainly the effects of exercise on grip strength. The most cited articles were consensus guidelines published by the working group on sarcopenia in the elderly from different continents. The prevention and rehabilitation of sarcopenia in the elderly are gaining attention. Current primary exercise therapies for sarcopenia and exercise combined with nutritional supplementation have significant advantages and the potential to delay muscle decay. This suggests a promising area for future research that could benefit from further advances.

Study on the Effect of Calcium Alloy on Arsenic Removal from Scrap-Based Steel Production.

Scrap steel is a kind of resource that can be recycled indefinitely. However, the enrichment of arsenic in the recycling process will seriously affect the performance of the product, making the recycling process unsustainable. In this study, the removal of arsenic from molten steel using calcium alloys was investigated experimentally, and the underlying mechanism was explored based on thermodynamic principles. The results show that the addition of calcium alloy is an effective means of reducing the arsenic content in molten steel, with the highest removal percentage of 56.36% observed with calcium aluminum alloy. A thermodynamic analysis revealed that the critical calcium content required for arsenic removal reaction is 0.0037%. Moreover, ultra-low levels of oxygen and sulfur were found to be crucial in achieving a good arsenic removal effect. When the arsenic removal reaction occurs in molten steel, the oxygen and sulfur concentrations in equilibrium with calcium were wO=0.0012% and wS=0.00548%, respectively. After successful arsenic removal, the arsenic removal product of the calcium alloy is Ca3As2, which usually does not appear alone. Instead, it is prone to combining with alumina, calcium oxide, and other inclusions to form composite inclusions, which is beneficial for the floating removal of inclusions and the purification of scrap steel in molten steel.

Fast generation of calculated ADF-EDX scattering cross-sections under channelling conditions.

Advanced materials often consist of multiple elements which are arranged in a complicated structure. Quantitative scanning transmission electron microscopy is useful to determine the composition and thickness of nanostructures at the atomic scale. However, significant difficulties remain to quantify mixed columns by comparing the resulting atomic resolution images and spectroscopy data with multislice simulations where dynamic scattering needs to be taken into account. The combination of the computationally intensive nature of these simulations and the enormous amount of possible mixed column configurations for a given composition indeed severely hamper the quantification process. To overcome these challenges, we here report the development of an incoherent non-linear method for the fast prediction of ADF-EDX scattering cross-sections of mixed columns under channelling conditions. We first explain the origin of the ADF and EDX incoherence from scattering physics suggesting a linear dependence between those two signals in the case of a high-angle ADF detector. Taking EDX as a perfect incoherent reference mode, we quantitatively examine the ADF longitudinal incoherence under different microscope conditions using multislice simulations. Based on incoherent imaging, the atomic lensing model previously developed for ADF is now expanded to EDX, which yields ADF-EDX scattering cross-section predictions in good agreement with multislice simulations for mixed columns in a core-shell nanoparticle and a high entropy alloy. The fast and accurate prediction of ADF-EDX scattering cross-sections opens up new opportunities to explore the wide range of ordering possibilities of heterogeneous materials with multiple elements.

Element Specific Atom Counting at the Atomic Scale by Combining High Angle Annular Dark Field Scanning Transmission Electron Microscopy and Energy Dispersive X-ray Spectroscopy.

A new methodology is presented to count the number of atoms in multimetallic nanocrystals by combining energy dispersive X-ray spectroscopy (EDX) and high angle annular dark field scanning transmission electron microscopy (HAADF STEM). For this purpose, the existence of a linear relationship between the incoherent HAADF STEM and EDX images is exploited. Next to the number of atoms for each element in the atomic columns, the method also allows quantification of the error in the obtained number of atoms, which is of importance given the noisy nature of the acquired EDX signals. Using experimental images of an Au@Ag core-shell nanorod, it is demonstrated that 3D structural information can be extracted at the atomic scale. Furthermore, simulated data of an Au@Pt core-shell nanorod show the prospect to characterize heterogeneous nanostructures with adjacent atomic numbers.

Levels and risk assessment of polycyclic aromatic hydrocarbons in wood vinegars from pyrolysis of biomass.

A method quantifying 16 polycyclic aromatic hydrocarbons (PAHs) in wood vinegars (WVs) obtained from slow pyrolysis of biomass with ultrasonic-assisted liquid-liquid extraction/gas chromatography-mass spectrometry (USALLE/GC-MS) was established. The recovery range was 83-128%, and the relative standard deviations (RSD%) were less than 15% except naphthalene, acenaphthylene and acenaphthene. Acenaphthylene, acenaphthene, fluorene, anthracene, phenanthrene, fluoranthene, and pyrene were observed in all samples and the other 9 compounds, including benzopyrene (B[a]P), were not detected. The concentration of ∑PAHs referred to the sum total of 7 PAHs mentioned above was 22.0-498.3 µg L-1. The PAHs concentration increased with the increasing pyrolysis temperature in bamboo willow WV, pinus sylvestris WV, and corncob WV, while it increased initially, and then decreased with a maximum at 550 °C in rice husk WV. The ∑PAHs concentration increased with a higher heating rate in the white pine WV, while rice husk WV and cornstalk WV showed the opposite trend. The varied condensed aromatic ring number showed that 3-ring PAHs relatively were the main component in all kind WVs. 3-ring PAHs increased with increasing temperatures, while 4-ring PAHs showed an opposite trend in sawdust WV and corncob WVs. A higher cellulose content in sawdust enhanced the reaction of lignin leading to a higher concentration of PAHs than that in straws and leaves. Calculations of the toxicity equivalents of PAHs in WVs indicated that anthracene was the most toxic among the PAHs, and the pinus sylvestris WV had the highest risk of ∑PAHs toxicity in all WVs.

Measuring Multidimensional Health Poverty in China.

This article defines the concept of "multidimensional health poverty," considering both the monetary aspects and multidimensional health deprivation of health poverty. Moreover, we set up the multidimensional health poverty index (MHPI) to measure health poverty in China by revising the traditional A-F MPI method, specifically we use the Catastrophic Health Expenditure (CHE) as a sufficient condition and income poverty as a necessary condition, and take physical, mental, and social health into account. The measurement result evidences that physical health, monetary dimensions (CHE and income poverty), and mental health contribute most to health poverty in China. In addition, the MHPI is significantly higher in rural areas than urban because of higher out-of-pocket medical payments and health deprivation in more dimensions. Compared with the traditional method, the MHPI is more accurate, stable, and comprehensive, making it more suitable for measuring health poverty.

Ovarian Dysfunction Induced by Chronic Whole-Body PM2.5 Exposure.

Fine particulate matter (PM2.5) pollution arouses public health concerns over the world. Increasing epidemiologic evidence suggests that exposure to ambient airborne PM2.5 increases the risk of female infertility. However, relatively few studies have systematically explored the harmful effect of chronic PM2.5 exposure on ovarian function and the underlying mechanisms. In this study, female C57BL/6J mice are exposed to filtered air or urban airborne PM2.5 for 4 months through a whole-body exposure system. It is found that PM2.5 exposure significantly caused the alteration of estrus cycles, reproductivity, hormone levels, and ovarian reserve. The granulosa cell apoptosis via the mitochondria dependent pathway contributes to the follicle atresia. With RNA-sequencing technique, the differentially expressed genes induced by PM2.5 exposure are mainly enriched in ovarian steroidogenesis, reactive oxygen species and oxidative phosphorylation pathways. Furthermore, it is found that increased PM2.5 profoundly exacerbated ovarian oxidative stress and inflammation in mice through the NF-κB/IL-6 signaling pathway. Notably, dietary polydatin (PD) supplement has protective effect in mice against PM2.5-induced ovarian dysfunction.These striking findings demonstrate that PM2.5 and/or air pollution is a critical factor for ovarian dysfunction through mitochondria-dependent and NF-κB/IL-6-mediated pathway, and PD may serve as a pharmaceutic candidate for air pollution-associated ovarian dysfunction.

Urban airborne PM2.5-activated microglia mediate neurotoxicity through glutaminase-containing extracellular vesicles in olfactory bulb.

Emerging evidence has showed that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is associated with neurodegeneration. Our previous studies in vitro found that PM2.5 exposure causes primary neurons damage through activating microglia. However, the molecular mechanism of microglia-mediated neurotoxicity remains to elucidate. In this study, five groups (N = 13 or 10) of six-week-old male C57BL/6 mice were daily exposed to PM2.5 (0.1 or 1 mg/kg/day body weight), Chelex-treated PM2.5 (1 mg/kg/day body weight), PM2.5 (1 mg/kg/day body weight) plus CB-839 (glutaminase inhibitor), or deionized water by intranasal instillation for 28 days, respectively. Compared with the control groups, We found that PM2.5 triggered reactive oxygen species (ROS) generation and microglia activation evidenced by significant increase of ionized calcium binding adaptor molecule-1 (IBa-1) staining in the mouse olfactory bulbs (OB). Data from transmission electron microscope (TEM) images and Western blot analysis showed that PM2.5 significantly increased extracellular vesicles (EVs) release from OB or murine microglial line BV2 cells, and glutaminase C (GAC) expression and glutamate generation in isolated OB and BV2 cells. However, treatment with N-acetylcysteine (NAC) or CB-839 significantly diminished the number of EVs and the expression of GAC and abolished PM2.5-induced neurotoxicity. These findings provide new insights that PM2.5 induces oxidative stress and microglia activation through its metal contents and glutaminase-containing EVs in OBs, which may serve as a potential pathway/mechanism of excessive glutamate generation in PM2.5-induced neurotoxicity.

Transforming solid-state precipitates via excess vacancies.

Many phase transformations associated with solid-state precipitation look structurally simple, yet, inexplicably, take place with great difficulty. A classic case of difficult phase transformations is the nucleation of strengthening precipitates in high-strength lightweight aluminium alloys. Here, using a combination of atomic-scale imaging, simulations and classical nucleation theory calculations, we investigate the nucleation of the strengthening phase θ' onto a template structure in the aluminium-copper alloy system. We show that this transformation can be promoted in samples exhibiting at least one nanoscale dimension, with extremely high nucleation rates for the strengthening phase as well as for an unexpected phase. This template-directed solid-state nucleation pathway is enabled by the large influx of surface vacancies that results from heating a nanoscale solid. Template-directed nucleation is replicated in a bulk alloy as well as under electron irradiation, implying that this difficult transformation can be facilitated under the general condition of sustained excess vacancy concentrations.

Epitranscriptomic 5-Methylcytosine Profile in PM2.5-induced Mouse Pulmonary Fibrosis.

Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.

High areal capacitance of vanadium oxides intercalated Ti3C2 MXene for flexible supercapacitors with high mass loading.

Flexible all-solid-state supercapacitors (ASSSs) have caught the scientific attention to meet the explosive demand for portable and wearable electronic devices. However, it is difficult for flexible electrode materials to obtain a high areal capacitance at a high mass loading, which limits their commercial applications. In this study, vanadium oxide (V2O5) nanoparticles are introduced into Ti3C2 flakes with the aid of cetyltrimethylammonium bromide (CTAB). The intercalation of V2O5 particles in the interlayer of Ti3C2 establishes a hierarchical structure and facilitates the electrolyte penetration. As a result, the prepared CT-Ti3C2@V2O5 composite electrode achieves a high areal capacitance of 2065 mF cm-2 at 3 mA cm-2 and superior active mass loading (15 mg cm-2). Meanwhile, over 93% capacitance is maintained after 6000 cycles at 18 mA cm-2. The ASSS based on CT-Ti3C2@V2O5 delivers a high areal capacitance of 477 mF cm-2 at 1 mV s-1 and exhibits stable performance at different bending states, which reaches to the advanced level for the ASSSs based on MXenes.

A Simple, Yet Multifunctional, Nanoformulation for Eradicating Tumors and Preventing Recurrence with Safely Low Administration Dose.

Designing simple-structured nanomedicine without lacking key functionalities, thereby avoiding incomplete damage or relapse of tumor with the administration of a safe dose, is pivotal for successful cancer nanotherapy. We herein presented a nanomedicine of photodynamic therapy (PDT) that simply assembled amphiphilic macromolecules of poly-l-lysine conjugating with photosensitizers onto hydrophobic upconverting nanoparticles. We demonstrated that the nanoformulation, despite its simple structure and synthesis, simultaneously possesses multiple features, including substantial payload of photosensitizers, avid cellular internalization both in vitro and in vivo, efficient diffusion and broad distribution in tumor lesion, and potent fatality for cancer stem cells that are refractory to other therapy modalities. Because of the combination of these functionalities, the tumors in mice were eradicated and no relapse was observed after at least 40 days, just with an extremely low intraperitoneal injection dose of 5.6 mg/kg. Our results suggested a strategy for designing multifunctional nanomedicines with simple construct and efficacious therapeutic response and presented the promising potential of PDT for a radical cure of cancer.

The effect of exposure time and concentration of airborne PM2.5 on lung injury in mice: A transcriptome analysis.

The association between airborne fine particulate matter (PM2.5) concentration and the risk of respiratory diseases has been well documented by epidemiological studies. However, the mechanism underlying the harmful effect of PM2.5 has not been fully understood. In this study, we exposed the C57BL/6J mice to airborne PM2.5 for 3 months (mean daily concentration ~50 or ~110 µg/m3, defined as PM2.5-3L or PM2.5-3H) or 6 months (mean daily concentration ~50 µg/m3, defined as PM2.5-6L) through a whole-body exposure system. Histological and biochemical analysis revealed that PM2.5-3H exposure caused more severe lung injury than did PM2.5-3L, and the difference was greater than that of PM2.5-6L vs PM2.5-3L exposure. With RNA-sequencing technique, we found that the lungs exposed with different concentration of PM2.5 have distinct transcriptional profiles. PM2.5-3H exposure caused more differentially expressed genes (DEGs) in lungs than did PM2.5-3L or PM2.5-6L. The DEGs induced by PM2.5-3L or PM2.5-6L exposure were mainly enriched in immune pathways, including Hematopoietic cell lineage and Cytokine-cytokine receptor interaction, while the DEGs induced by PM2.5-3H exposure were mainly enriched in cardiovascular disease pathways, including Hypertrophic cardiomyopathy and Dilated cardiomyopathy. In addition, we found that upregulation of Cd5l and reduction of Hspa1 and peroxiredoxin-4 was associated with PM2.5-induced pulmonary inflammation and oxidative stress. These results may provide new insight into the cytotoxicity mechanism of PM2.5 and help to development of new strategies to attenuate air pollution associated respiratory disease.

SPIDR significantly suppressed in tissues of small cell lung cancer promotes NCI-H446 cells proliferation by reducing serum dependence / 中国肿瘤生物治疗杂志

@# Objective: The present study was aimed to explore the role and distinctive mechanism of SPIDR, the key regulatory protein of homologous recombination pathway, in progression of small cell lung cancer (SCLC). Methods: 60 SCLC specimens and 44 normal lung tissues were collected from the patients undergoing tumor resection and bronchoscopic puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2013 to January 2015. The expression of SPIDR in clinical samples and NCIH446 (SCLC cell line) and MRC-5 (normal cell line) were assayed by Real-time PCR. The role of SPIDR in SCLC was investigated in vivo and in vitro by the expression of SPIDR were artificially modified in NCI-H446. Results: Smoking was significantly associated with the occurrence of SCLC (P<0.01). The expression of SPIDR mRNAin SCLC tissues was lower than that of normal lung tissues (P <0.01), and the SPIDR transcriptional and translational levels of NCI-H446 cells were also lower than that of MRC-5.Although there is no significant changes of cell growth rate and susceptibility to cisplatin and etoposide in the NCI-H446 cells overexpressing SPIDR. However, the volume of xenograft tumors of overexpressed SPIDR group decreased by 58.99% (P<0.01) and 61.84% (P<0.01) than that of the original NCI-H446 cells and the NCI-H446 cells transfected with vector (pMSCV) and the average tumor mass decreased by 61.70% (P<0.01) and 70.25% (P<0.01) respectively. When the fetal bovine serum content in the medium was reduced to 3%, the growth rate of NCI-H446 cells overexpressing SPIDR was 22.33% (P<0.01) and 20.24% (P<0.05) lower than that of the original NCIH446 cells and control group, the similar results were obtained from the 1% serum concentration experiment as well. Conclusion: The expression of SPIDR, the key regulatory protein in the DNAdouble strand break homologous recombination repair pathway, was significantly suppressed in SCLC tissues, which markedly accelerated the growth of NCI-H446 cells in vivo and reduced the reliance of NCIH446 cells to the serum. The detailed mechanism is worthy of further investigation.

An efficient RFID authentication protocol to enhance patient medication safety using elliptic curve cryptography.

Medication errors are very dangerous even fatal since it could cause serious even fatal harm to patients. In order to reduce medication errors, automated patient medication systems using the Radio Frequency Identification (RFID) technology have been used in many hospitals. The data transmitted in those medication systems is very important and sensitive. In the past decade, many security protocols have been proposed to ensure its secure transition attracted wide attention. Due to providing mutual authentication between the medication server and the tag, the RFID authentication protocol is considered as the most important security protocols in those systems. In this paper, we propose a RFID authentication protocol to enhance patient medication safety using elliptic curve cryptography (ECC). The analysis shows the proposed protocol could overcome security weaknesses in previous protocols and has better performance. Therefore, the proposed protocol is very suitable for automated patient medication systems.