HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir.

First Report of Powdery Mildew on Cardamine violifolia in China.

Cardamine violifolia, also called Cardamine hupingshanensis, is an economically important medicinal plant renowned for accumulating selenium (Guo et al., 2022). Selenium is an essential trace element with anti-oxidant, anti-inflammatory, anti-cancer, and immune regulatory functions. In July 2023, an outbreak of powdery mildew was detected, infecting the leaves of numerous C. violifolia plants in Enshi (30°11'5.27''N; 109°48'48.45''E), Hubei Province, China. This disease caused severe damage to plant leaves and stems, starting as individual spots and merging into a large mold that covers the entire leaf. It affected nearly 25% all C. violifolia plants, resulting in significant yield loss, disruption of normal metabolism, and premature aging. The lower leaf blades and underside of the leaves were particularly vulnerable. The affected leaves were collected and subjected to morphological diagnostic analysis (Mori et al., 2000) (Fig. S1). The powdery mildew species aggressively spread throughout the leaves, pedicels, and pods, persisting until present and often covering the entire surface. The conidiophores were upright, cylindrical, composed of 3 to 4 cells, and measured 92.3 ± 12.9 × 9.2 ± 0.6 µm (n = 30). Conidial pedicels had 21.6 ± 3.4 µm (n = 50) long cylindrical podocytes. The monoconidia were columnar or barrel-columnar, 30.60-55.59 × 9.11-20.00 µm in size. Conidia lacked an obvious cellulose body. The bud tubes formed from the end of conidia, and papillary appressoria developed on the epiphytic mycelia. ITS region sequences were amplified using the specific powdery mildew universal primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3'), PM6 (5'-GYCRCYCTGTCGCGAG-3') for partial sequences of 18S and 28S ribosomal DNA genes (Takamatsu et al., 2001). The sequence was deposited in the GenBank under the accession number OR506156 and aligned with available sequences on NCBI, which were 99.2%(528/532) identical to the E. cruciferarum (MT309701, MF192845, and KY660929) sequences (Fig. S2). The ITS sequence from GenBank was used to conduct maximum likelihood phylogenetic analysis using MEGA 11.0. The analysis results showed both the strain and E. cruciferarum clustered on the same branch. To confirm Koch's postulates, pathogenicity testing was carried out using an illuminating incubator. Infected leaves were attached to healthy leaves of C. violifolia seedlings (n=8). All the plants were incubated under 25℃ and >80% relative humidity. After one month, all inoculated plants presented the same symptoms as those initially observed in the field. Morphological and molecular analysis confirmed the isolated fungi's identity as the same pathogen. Therefore, C. violifolia is a suitable host for E. cruciferarum in China. The growers must be informed of these findings to prevent serious economic losses caused by this pathogenic white powder and to prepare for proper management practices. To our knowledge, this is the first report of E. cruciferarum infecting C. violifolia in China.

Human-in-the-Loop Trajectory Optimization Based on sEMG Biofeedback for Lower-Limb Exoskeleton.

Lower-limb exoskeletons (LLEs) can provide rehabilitation training and walking assistance for individuals with lower-limb dysfunction or those in need of functionality enhancement. Adapting and personalizing the LLEs is crucial for them to form an intelligent human-machine system (HMS). However, numerous LLEs lack thorough consideration of individual differences in motion planning, leading to subpar human performance. Prioritizing human physiological response is a critical objective of trajectory optimization for the HMS. This paper proposes a human-in-the-loop (HITL) motion planning method that utilizes surface electromyography signals as biofeedback for the HITL optimization. The proposed method combines offline trajectory optimization with HITL trajectory selection. Based on the derived hybrid dynamical model of the HMS, the offline trajectory is optimized using a direct collocation method, while HITL trajectory selection is based on Thompson sampling. The direct collocation method optimizes various gait trajectories and constructs a gait library according to the energy optimality law, taking into consideration dynamics and walking constraints. Subsequently, an optimal gait trajectory is selected for the wearer using Thompson sampling. The selected gait trajectory is then implemented on the LLE under a hybrid zero dynamics control strategy. Through the HITL optimization and control experiments, the effectiveness and superiority of the proposed method are verified.

Comprehensive analysis of lncRNA-mediated ceRNA regulatory networks and key genes associated with papillary thyroid cancer coexistent with Hashimoto's thyroiditis.

OBJECTIVE: The incidence of papillary thyroid cancer (PTC) concomitant with Hashimoto's thyroiditis (HT) is gradually increasing over the past decades. This study aims to identify differentially expressed lncRNAs between tumor tissues of PTC with or without HT and further to confer a better understanding of lncRNA-based competing endogenous RNA (ceRNA) network in PTC with HT. METHODS: GSE138198 containing tissue mRNA data and GSE192560 containing lncRNA data were utilized to perform differentially expression analysis. The ceRNA network was constructed based on miRNA-mRNA interactions merging with lncRNA-microRNA interactions. Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed. The mRNA levels of core genes in the PPI analysis in tumor tissues collected from 112 PTC patients including 35 cases coexistent with HT were determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 57 genes and 40 lncRNAs, with value of |log2 fold change (FC)|≥ 1 and the adjusted P-value < 0.05, were deemed as differentially expressed genes and lncRNAs between PTC with and without HT. The pathways most significantly enriched by differentially expressed genes between PTC with and without HT were viral protein interaction with cytokine and cytokine receptor and cytokine-cytokine receptor interaction. CXCL10, CXCL9, CCL5, FCGR3A, and CCR2 owned degree values not less than 10 were deemed as core genes differentially expressed between PTC with and without HT. A total of 76 pairs of lncRNA-miRNA-mRNA ceRNA were obtained. Results of qRT-PCR partially demonstrated the bioinformatics results that the mRNA levels of CXCL10, CXCL9, CCL5, and CCR2 were remarkably elevated in tumor tissues collected from PTC patients coexistent with HT than those without HT (P < 0.001). CONCLUSION: Our study offers a better understanding of the lncRNA-related ceRNA network involved in PTC with HT, providing novel key genes associated with PTC coexistent with HT.

The C-terminal domain of feline and bovine SAMHD1 proteins has a crucial role in lentiviral restriction.

SAM and HD domain-containing protein 1 (SAMHD1) is a host factor that restricts reverse transcription of lentiviruses such as HIV in myeloid cells and resting T cells through its dNTP triphosphohydrolase (dNTPase) activity. Lentiviruses counteract this restriction by expressing the accessory protein Vpx or Vpr, which targets SAMHD1 for proteasomal degradation. SAMHD1 is conserved among mammals, and the feline and bovine SAMHD1 proteins (fSAM and bSAM) restrict lentiviruses by reducing cellular dNTP concentrations. However, the functional regions of fSAM and bSAM that are required for their biological functions are not well-characterized. Here, to establish alternative models to investigate SAMHD1 in vivo, we studied the restriction profile of fSAM and bSAM against different primate lentiviruses. We found that both fSAM and bSAM strongly restrict primate lentiviruses and that Vpx induces the proteasomal degradation of both fSAM and bSAM. Further investigation identified one and five amino acid sites in the C-terminal domain (CTD) of fSAM and bSAM, respectively, that are required for Vpx-mediated degradation. We also found that the CTD of bSAM is directly involved in mediating bSAM's antiviral activity by regulating dNTPase activity, whereas the CTD of fSAM is not. Our results suggest that the CTDs of fSAM and bSAM have important roles in their antiviral functions. These findings advance our understanding of the mechanism of fSAM- and bSAM-mediated viral restriction and might inform strategies for improving HIV animal models.

Recent developments in filtration media and respirator technology in response to COVID-19.

Abstract: The COVID-19 pandemic triggered a surge in demand for N95 or equivalent respirators that the global supply chain was unable to satisfy. This shortage in critical equipment has inspired research that addresses the immediate problems and has accelerated the development of the next-generation filtration media and respirators. This article provides a brief review of the most recent work with regard to face respirators and filtration media. We discuss filtration efficiency of the widely utilized cloth masks. Next, the sterilization of and reuse of existing N95 respirators to extend the existing stockpile is discussed. To expand near-term supplies, optimization of current manufacturing methods, such as melt-blown processes and electrospinning, has been explored. Future manufacturing methods have been investigated to address long-term supply shortages. Novel materials with antiviral and sterilizable properties with the ability for multiple reuses have been developed and will contribute to the development of the next generation of longer lasting multi-use N95 respirators. Finally, additively manufactured respirators are reviewed, which enable a rapidly deployable source of reusable respirators that can use any filtration fabric.

Chemical characteristics, oxidative potential, and sources of PM2.5 in wintertime in Lahore and Peshawar, Pakistan.

The chemical characteristics, oxidative potential, and sources of PM2.5 were analyzed at the urban sites of Lahore and Peshawar, Pakistan in February 2019. Carbonaceous species, water soluble ions, and metal elements were measured to investigate the chemical composition and sources of PM2.5. The dithiothreitol (DTT) consumption rate was measured to evaluate the oxidative potential of PM2.5. Both cities showed a high exposure risk of PM2.5 regarding its oxidative potential (DTTv). Carbonaceous and some of the elemental species of PM2.5 correlated well with DTTv in both Lahore and Peshawar. Besides, the DTTv of PM2.5 in Lahore showed significant positive correlation with most of the measured water soluble ions, however, ions were DTT-inactive in Peshawar. Due to the higher proportions of carbonaceous species and metal elements, Peshawar showed higher mass-normalized DTT activity of PM2.5 compared to Lahore although the average PM2.5 concentration in Peshawar was lower. The high concentrations of toxic metals also posed serious non-carcinogenic and carcinogenic risks to the residents of both cities. Principle component analysis coupled with multiple linear regression was applied to investigate different source contributions to PM2.5 and its oxidative potential. Mixed sources of traffic and road dust resuspension and coal combustion, direct vehicle emission, and biomass burning and formation of secondary aerosol were identified as the major sources of PM2.5 in both cities. The findings of this study provide important data for evaluation of the potential health risks of PM2.5 and for formulation of efficient control strategies in major cities of Pakistan.

Characterizing heterogeneity of non-small cell lung tumour microenvironment to identify signature prognostic genes.

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in non-small cell lung cancer (NSCLC). This study focused on the characterization of immune infiltration profiling in patients with NSCLC and its correlation with survival outcome. All TCGA samples were divided into three heterogeneous clusters based on immune cell profiles: cluster 1 ('low infiltration' cluster), cluster 2 ('heterogeneous infiltration' cluster) and cluster 3 ('high infiltration' cluster). The immune cells were responsible for a significantly favourable prognosis for the 'high infiltration' community. Cluster 1 had the lowest cytotoxic activity, tumour-infiltrating lymphocytes and interferon-gamma (IFN-γ), as well as immune checkpoint molecules expressions. In addition, MHC-I and immune co-stimulator were also found to have lower cluster 1 expressions, indicating a possible immune escape mechanism. A total of 43 differentially expressed genes (DEGs) that overlapped among the groups were determined based on three clusters. Finally, based on a univariate Cox regression model, prognostic immune-related genes were identified and combined to construct a risk score model able to predict overall survival (OS) rates in the validation datasets.

Output voltage control of DAB converters based on uncertainty and disturbance estimation.

The dual active bridge (DAB) converter is a power electronic device commonly used for DC voltage regulation and stabilization. However, during its control process, external disturbances, load variations, input voltage variations, switching tube voltage drops, dead time, etc. lead to errors in the control output, thus reducing the control accuracy of the system. Therefore, this article propose a robust control scheme for the output voltage based on uncertainty and disturbance estimator. In this article, an average small-signal model of the dual active bridge converter was established in terms of the basic principles and operation mechanisms, simplifying the controller's design. Then, the basic principles of the uncertainty and disturbance estimator (UDE) are introduced. The small-signal model of the dual active bridge (DAB) converter is applied to the UDE to minimize output voltage error by enabling the controller to directly regulate the shift ratio. Finally, this article discusses the application and effectiveness of the uncertainty and disturbance estimator (UDE) in the simulation and control of dual active bridge (DAB) converters. A series of experimental comparative studies are conducted, demonstrating that this scheme offers significant advantages in suppressing system uncertainties and disturbances.

Fine particulate matter from brick kilns site and roadside in Lahore, Pakistan: Insight into chemical composition, oxidative potential, and health risk assessment.

Background: Human health is seriously threatened by particulate matter (PM) pollution, which is a major environmental problem. A better indicator of biological responses to PM exposure than its mass alone is the PM "oxidative potential (OP)," or ability to oxidize target molecules. When reactive oxygen species (ROS) are generated in the OP in excess of the antioxidant capacity of body due to PM components such metals and organic species, it causes inflammation, deoxyribonucleic acid (DNA), proteins, and lipids damage. Method: The samples of fine particulate matter (PM2.5) are collected from the brick kiln site and the roadside in Lahore, Pakistan. The organic carbon (OC) and elemental carbon (EC) were estimated by carbon analyzer (DRI 2001A) using the thermal/optical transmittance (TOT) protocol. The water-soluble organic carbon (WSOC) concentration was determined using a total organic carbon analyzer (Shimadzu TOC-L CPN). Ion chromatography (Dionex ICS-900) with a conductivity detector was used to analyze the water-soluble anions (Cl-, NO3-, and SO42-) and cations (NH4+, Na+, K+, Mg2+, and Ca2+). Inductively coupled plasma-mass spectrometry (iCAP TQ ICP-MS, Thermo Scientific) was used to determine the concentrations of metals in the solution. The dithiothreitol (DTT) consumption rate was calculated using a spectrophotometer at a wavelength of 412 nm. Results: The mean concentrations of PM2.5 at the brick kiln site and roadside reported are 509.3 ± 32.3 µg/m3 and 467.5 ± 24.9 µg/m3, and the average OC/EC ratio is 1.9 ± 0.4 and 2.1 ± 0.1. primary organic carbon (POC) contributed more to OC than secondary organic carbon (SOC), which indicated the dominance of primary combustion sources. The anion equivalent (AE) to cation equivalent (CE) ratio indicated that PM2.5 is acidic at both sites due to the dominance of NO3- and SO42-. The DTT consumption rate normalized by PM2.5 mass (DTTm) and DTT consumption rate normalized by air volume (DTTv) of PM2.5 at the roadside samples are higher than at the brick kiln site due to the higher contribution of ionic species to the mass of PM2.5. Carbonaceous species of PM2.5 at both sampling sites are significantly correlated with DTTv of PM2.5, while metallic species behaved differently. The incremental lifetime cancer risk (ILCR) values (lung cancer) of As and Cr at both sampling sites, while the ILCR value of Cd at the roadside samples is exceeding the permissible limits for adults and children. The lifetime average daily dose (LADD) value for adults is higher than that for children, indicating that children are less vulnerable to metals. Conclusion: The concentration of PM2.5 at both sampling sites were exceeding the permissible limits of Pakistan' National Environmental Quality Standard (NEQS) and posing risk to the health of the local population. The POC and SOC contribution to OC at the brick kiln site and roadside in Lahore were 84.6%, 15.4% and 84.4%, 15.6%. POC at both sampling sites were the dominant carbon species indicating the dominance of primary combustion sources. The residence of Lahore poses the lung cancer risk due to Cr, As, and Cd at both sampling sites. The results of this study provide important data and evidence for further evaluation of the potential health risks of PM2.5 from brick kiln site and road side in Pakistan and formulation of efficient air-pollution control measures.

Important Role of Ion Flux Regulated by Separators in Lithium Metal Batteries.

Polyolefin separators are the most common separators used in rechargeable lithium (Li)-ion batteries. However, the influence of different polyolefin separators on the performance of Li metal batteries (LMBs) has not been well studied. By performing particle injection simulations on the reconstructed three-dimensional pores of different polyethylene separators, it is revealed that the pore structure of the separator has a significant impact on the ion flux distribution, the Li deposition behavior, and consequently, the cycle life of LMBs. It is also discovered that the homogeneity factor of Li-ion toward Li metal electrode is positively correlated to the longevity and reproducibility of LMBs. This work not only emphasizes the importance of the pore structure of polyolefin separators but also provides an economic and effective method to screen favorable separators for LMBs.

Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform.

Reverse genetic systems enable the engineering of RNA virus genomes and are instrumental in studying RNA virus biology. With the recent outbreak of the coronavirus disease 2019 pandemic, already established methods were challenged by the large genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA viruses with high sequence fidelity using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment - harboring all heterologous sequences - viral RNA can directly serve as a template for manipulating and rescuing recombinant mutant virus, without any cloning step. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate their biology. To demonstrate its potential as a reverse genetics platform for plus-stranded RNA viruses, the protocol has been successfully applied for the cloning-free rescue of recombinant Chikungunya and Dengue virus.

Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform.

Reverse genetic systems enable the engineering of RNA virus genomes and are instrumental in studying RNA virus biology. With the recent outbreak of the COVID-19 pandemic, already established methods were challenged by the large genome of SARS-CoV-2. Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA viruses with high sequence fidelity, using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment - harboring all heterologous sequences - viral RNA can directly serve as a template for manipulating and rescuing recombinant mutant virus, without any cloning step. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate their biology. To demonstrate its potential as a reverse genetics platform for plus-stranded RNA viruses, the protocol has been successfully applied for the cloning-free rescue of recombinant Chikungunya and Dengue virus.

Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods.

While combination therapy completely suppresses HIV-1 replication in blood, functional virus persists in CD4+ T cell subsets in non-peripheral compartments that are not easily accessible. To fill this gap, we investigated tissue-homing properties of cells that transiently appear in the circulating blood. Through cell separation and in vitro stimulation, the HIV-1 "Gag and Envelope reactivation co-detection assay" (GERDA) enables sensitive detection of Gag+/Env+ protein-expressing cells down to about one cell per million using flow cytometry. By associating GERDA with proviral DNA and polyA-RNA transcripts, we corroborate the presence and functionality of HIV-1 in critical body compartments utilizing t-distributed stochastic neighbor embedding (tSNE) and density-based spatial clustering of applications with noise (DBSCAN) clustering with low viral activity in circulating cells early after diagnosis. We demonstrate transcriptional HIV-1 reactivation at any time, potentially giving rise to intact, infectious particles. With single-cell level resolution, GERDA attributes virus production to lymph-node-homing cells with central memory T cells (TCMs) as main players, critical for HIV-1 reservoir eradication.

Understanding the Influence of Li7La3Zr2O12 Nanofibers on Critical Current Density and Coulombic Efficiency in Composite Polymer Electrolytes.

Composite polymer electrolytes (CPEs) are attractive materials for solid-state lithium metal batteries, owing to their high ionic conductivity from ceramic ionic conductors and flexibility from polymer components. As with all lithium metal batteries, however, CPEs face the challenge of dendrite formation and propagation. Not only does this lower the critical current density (CCD) before cell shorting, but the uncontrolled growth of lithium deposits may limit Coulombic efficiency (CE) by creating dead lithium. Here, we present a fundamental study on how the ceramic components of CPEs influence these characteristics. CPE membranes based on poly(ethylene oxide) and lithium bis(trifluoromethanesulfonyl)imide (PEO-LiTFSI) with Li7La3Zr2O12 (LLZO) nanofibers were fabricated with industrially relevant roll-to-roll manufacturing techniques. Galvanostatic cycling with lithium symmetric cells shows that the CCD can be tripled by including 50 wt % LLZO, but half-cell cycling reveals that this comes at the cost of CE. Varying the LLZO loading shows that even a small amount of LLZO drastically lowers the CE, from 88% at 0 wt % LLZO to 77% at just 2 wt % LLZO. Mesoscale modeling reveals that the increase in CCD cannot be explained by an increase in the macroscopic or microscopic stiffness of the electrolyte; only the microstructure of the LLZO nanofibers in the PEO-LiTFSI matrix slows dendrite growth by presenting physical barriers that the dendrites must push or grow around. This tortuous lithium growth mechanism around the LLZO is corroborated with mass spectrometry imaging. This work highlights important elements to consider in the design of CPEs for high-efficiency lithium metal batteries.

Micro/Nanorobots for Medical Diagnosis and Disease Treatment.

Micro/nanorobots are functional devices in microns, at nanoscale, which enable efficient propulsion through chemical reactions or external physical field, including ultrasonic, optical, magnetic, and other external fields, as well as microorganisms. Compared with traditional robots, micro/nanorobots can perform various tasks on the micro/nanoscale, which has the advantages of high precision, strong flexibility, and wide adaptability. In addition, such robots can also perform tasks in a cluster manner. The design and development of micro/nanorobots and the integration of surface functionalization, remote drive system, and imaging tracking technology will become a key step for their medical applications in organisms. Thus, micro/nanorobots are expected to achieve more efficient and accurate local diagnosis and treatment, and they have broad application prospects in the biomedical field. This paper aims to introduce relevant driving methods of micro/nanorobots preparation in detail, summarizes the progress of research in medical applications, and discusses the challenges it faces in clinical applications and the future direction of development.

Oxidative potential associated with water-soluble components of PM2.5 in Beijing: The important role of anthropogenic organic aerosols.

Oxidative stress is the mainstream toxicological mechanism for the adverse health outcomes of ambient aerosols. However, our understanding of the crucial redox-active species affecting the oxidative potential of water-soluble aerosols (OPWS) remains limited. In this study, the OPWS of PM2.5 in Beijing was measured using dithiothreitol (DTT) assay, including DTT consumption rate and ·OH formation rate. OPWS was more closely related to water-soluble organic compounds (WSOC) rather than transition metals. Laboratory simulations were conducted to investigate the effects of individual target species in the context of complex metal-organic interactions. The results showed that reducing WSOC can effectively decrease OPWS, while reducing Cu2+ increased OPWS. Parallel factor analysis demonstrated that OPWS was the most significantly correlated with the highly oxidized humic-like or quinone-like substances. Multiple linear regression showed that aromatic secondary organic carbon (SOC) (34.4%), other primary combustion sources of WSOC (20.0%), primary biomass burning WSOC (19.8%), transition metal ions (12.9%) and biomass burning SOC (12.8%) made significant contributions to DTTV. In addition to the anthropogenic sources of WSOC, the aged biogenic SOC also contributed to OHV, particularly in summer. Reducing anthropogenic WSOC was the key to the effective control of OPWS of PM2.5 in Beijing.

In situ self-assembled peptide enables effective cancer immunotherapy by blockage of CD47.

Treatment of late-stage lung cancer has witnessed limited advances. In contrast to the tremendous efforts toward improving adaptive immunity, approaches to modulating innate immunity are relatively immature. As important innate immune cells, tumor-associated macrophages (TAMs) account for a substantial fraction of tumor-infiltrating lymphocytes, which not only reverses the immune-suppressive tumor microenvironment but also facilitates an adaptive immune response. In this study, we developed a tumor-specific MMP-2-responsive CD47 blockage (TMCB) strategy to enable effective cancer immunotherapy. Briefly, the matrix metalloproteinase-2 (MMP-2)-responsive self-assembly peptide specifically recognizes CD47, which is highly expressed in lung tumor cells. Second, the MMP-2-responsive self-assembly peptide is efficiently cleaved by MMP-2, which is overexpressed in the tumor microenvironment. Finally, the generated residual peptide naturally self-assembles into peptide-based nanofibers. The in situ constructed nanofibers inhibit the canonical CD47 "Do not eat me" signal expressed on tumor cells to promote phagocytosis of tumor cells by macrophages, which further induces effective antigen presentation and initiates T cell-mediated adaptive immune responses to inhibit tumor growth. Thus, we described a peptide-based TMCB strategy that induces both innate and adaptive immune systems to inhibit tumor growth.

Machine-Learning Algorithm-Based Prediction of Diagnostic Gene Biomarkers Related to Immune Infiltration in Patients With Chronic Obstructive Pulmonary Disease.

Objective: This study aims to identify clinically relevant diagnostic biomarkers in chronic obstructive pulmonary disease (COPD) while exploring how immune cell infiltration contributes towards COPD pathogenesis. Methods: The GEO database provided two human COPD gene expression datasets (GSE38974 and GSE76925; n=134) along with the relevant controls (n=49) for differentially expressed gene (DEG) analyses. Candidate biomarkers were identified using the support vector machine recursive feature elimination (SVM-RFE) analysis and the LASSO regression model. The discriminatory ability was determined using the area under the receiver operating characteristic curve (AUC) values. These candidate biomarkers were characterized in the GSE106986 dataset (14 COPD patients and 5 controls) in terms of their respective diagnostic values and expression levels. The CIBERSORT program was used to estimate patterns of tissue infiltration of 22 types of immune cells. Furthermore, the in vivo and in vitro model of COPD was established using cigarette smoke extract (CSE) to validated the bioinformatics results. Results: 80 genes were identified via DEG analysis that were primarily involved in cellular amino acid and metabolic processes, regulation of telomerase activity and phagocytosis, antigen processing and MHC class I-mediated peptide antigen presentation, and other biological processes. LASSO and SVM-RFE were used to further characterize the candidate diagnostic markers for COPD, SLC27A3, and STAU1. SLC27A3 and STAU1 were found to be diagnostic markers of COPD in the metadata cohort (AUC=0.734, AUC=0.745). Their relevance in COPD were validated in the GSE106986 dataset (AUC=0.900 AUC=0.971). Subsequent analysis of immune cell infiltration discovered an association between SLC27A3 and STAU1 with resting NK cells, plasma cells, eosinophils, activated mast cells, memory B cells, CD8+, CD4+, and helper follicular T-cells. The expressions of SLC27A3 and STAU1 were upregulated in COPD models both in vivo and in vitro. Immune infiltration activation was observed in COPD models, accompanied by the enhanced expression of SLC27A3 and STAU1. Whereas, the knockdown of SLC27A3 or STAU1 attenuated the effect of CSE on BEAS-2B cells. Conclusion: STUA1 and SLC27A3 are valuable diagnostic biomarkers of COPD. COPD pathogenesis is heavily influenced by patterns of immune cell infiltration. This study provides a molecular biology insight into COPD occurrence and in exploring new therapeutic means useful in COPD.