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The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health. We recently developed a novel and facile water-probe-based method for directly measuring of the pH for micrometer-size droplets, providing a promising technique to better understand aerosol acidity in the atmosphere. The complex chemical composition of fine particles in the ambient air, however, poses certain challenges to using a water-probe for pH measurement, including interference from interactions between compositions and the influence of similar compositions on water structure. To explore the universality of our method, it was employed to measure the pH of ammonium, nitrate, carbonate, sulfate, and chloride particles. The pH of particles covering a broad range (0-14) were accurately determined, thereby demonstrating that our method can be generally applied, even to alkaline particles. Furthermore, a standard spectral library was developed by integrating the standard spectra of common hydrated ions extracted through the water-probe. The library can be employed to identify particle composition and overcome the spectral overlap problem resulting from similar effects. Using the spectral library, all ions were identified and their concentrations were determined, in turn allowing successful pH measurement of multicomponent (ammonium-sulfate-nitrate-chloride) particles. Insights into the synergistic effect of Cl-, NO3-, and NH4+ depletion obtained with our approach revealed the interplay between pH and volatile partitioning. Given the ubiquity of component partitioning and pH variation in particles, the water probe may provide a new perspective on the underlying mechanisms of aerosol aging and aerosol-cloud interaction.

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HIV-infected cells persisting in the face of suppressive antiretroviral therapy are the barrier to curing infection. Cytotoxic immunoconjugates targeted to HIV antigens on the cell surface may clear these cells. We showed efficacy in mouse and macaque models using immunotoxins, but immunogenicity blunted the effect. As an alternative, we propose antibody drug conjugates (ADCs), as used in cancer immunotherapy. In cancer, the target is a dividing cell, whereas it may not be in HIV. We screened cytotoxic drugs on human primary cells and cell lines. An anthracycline derivative, PNU-159682 (PNU), was highly cytotoxic to both proliferating and resting cells. Human anti-gp41 mAb 7B2 was conjugated to ricin A chain or PNU. The conjugates were tested in vitro for cytotoxic efficacy and anti-viral effect, and in vivo for tolerability. The specificity of killing for both conjugates was demonstrated on Env+ and Env- cells. The toxin conjugate was more potent and killed more rapidly, but 7B2-PNU was effective at levels achievable in patients. The ricin conjugate was well tolerated in mice; 7B2-PNU was toxic when administered intraperitoneally but was tolerated intravenously. We have produced an ADC with potential to target the persistent HIV reservoir in both dividing and non-dividing cells while avoiding immunogenicity. Cytotoxic anti-HIV immunoconjugates may have greatest utility as part of an "activate and purge" regimen, involving viral activation in the reservoir. This is a unique comparison of an immunotoxin and ADC targeted by the same antibody and tested in the same systems.IMPORTANCEHIV infection can be controlled with anti-retroviral therapy, but it cannot be cured. Despite years of therapy that suppresses HIV, patients again become viremic shortly after discontinuing treatment. A long-lived population of memory T cells retain the genes encoding HIV, and these cells secrete infectious HIV when no longer suppressed by therapy. This is the persistent reservoir of HIV infection. The therapies described here use anti-HIV antibodies conjugated to poisons to kill the cells in this reservoir. These poisons may be of several types, including protein toxins (immunotoxins) or anti-cancer drugs (antibody drug conjugates, ADCs). We have previously shown that an anti-HIV immunotoxin had therapeutic effects in animal models, but it elicited an anti-drug immune response. Here, we have prepared an anti-HIV ADC, which would be less likely to provoke an immune response, and show its potential for use in eliminating the persistent reservoir of HIV infection.

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China faces challenges in reaching its carbon neutrality goal by the year 2060 to meet the Paris Agreement and improving air quality simultaneously. Dramatic nitrogen emission reductions will be brought by this ambitious target, yet their impact on the natural ecosystem is not clear. Here, by combining two atmospheric chemistry models and two process-based terrestrial ecosystem models constrained using nationwide measurements, we show that atmospheric nitrogen deposition in China's terrestrial land will decrease by 44-57% following two emission control scenarios including one aiming at carbon neutrality. They consequently result in a pronounced shrinkage in terrestrial net ecosystem production, by 11-20% depending on models and emission scenarios. Our results indicate that the nitrogen emission reductions accompanying decarbonization would undermine natural carbon sinks and in turn set back progress toward carbon neutrality. This unintended impact calls for great concern about the trade-offs between nitrogen management and carbon neutrality.

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BACKGROUND: Antibiotic residues in food chain have raised concerns regarding their toxicity and involvement in antimicrobial resistance. However, most existing antibiotic biosensors are primarily applicable to liquid food samples. Given the complex matrix characteristics of foods, there is an urgent need for the development of effective antibiotic detection platforms that exhibit high universality and flexibility. Porous microneedles (PMN) are microdevice structures with needle-like shapes and microscale pores throughout their composition, which facilitate rapid sampling. Consequently, the integration of PMN with biosensors holds significant promise for the detection of antibiotic residues in complex food samples. RESULTS: In this study, hydrogel-forming PMN are fabricated by leveraging the oxygen-production capacity of thylakoid to generate bubbles and form porous structures. These PMN are then integrated with a fluorescence aptasensor for the quantification of the antibiotic netilmicin. The aptasensor consists of a netilmicin (NET) aptamer with stem loop and hairpin structure, which facilitated the binding of SYBR Green I to produce a fluorescent signal. In the presence of NET, the complete binding between NET and the aptamer results in a reduction of fluorescence intensity, thereby generating a detectable signal change for the detection of NET. Utilizing capillary action accelerate fluid extraction (2.9 times faster than nonporous microneedles) and a large specific surface area (5.1072 m2/g) conducive to aptasensor adsorb, the PMN achieve efficient capture and quantification of antibiotic with limits of detection and quantitation of 5.99 nM and 19.8 nM, respectively. SIGNIFICANCE: Porous microneedles with tunable porosity and desirable mechanical properties are successfully fabricated. The integration of PMN with aptasensor enable the efficient detection of netilmicin in fish, milk and river water samples, demonstrating high recovery rates. The PMN represent potential tools for the convenient and rapid detection of antibiotic residues within complex food matrices, thereby enhancing food safety monitoring.

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Ice-nucleating particles (INPs) can initiate cloud ice formation, influencing cloud radiative effects (CRE) and climate. However, the knowledge of INP sources, concentrations, and their impact on CRE over the Tibetan Plateau (TP)-a highly climate-sensitive region-remains largely hypothetical. Here, we integrated data from multisource satellite observations and snowpack samples collected from five glaciers to demonstrate that dust particles constitute primary INP sources over the TP. The springtime dust influxes lead to seasonally elevated ice concentrations in mixed-phase clouds. Furthermore, the decadal reduction in dustiness from 2007 to 2019 results in decreased springtime dust INPs, thereby amplifying the cooling effect of clouds over the TP, with a 1.98 ± 0.39-watt per square meter reduction in surface net CRE corresponding to a 0.01 decrease in dust optical depth. Our findings elucidate previously unidentified pathways of climate feedback from an atmospheric INP perspective, especially highlighting the crucial role of dust in aerosol-cloud interactions.

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Beijing, with the highest number of motor vehicles in China, significantly contributes to O3 pollution through substantial NOx and VOC emissions in the on-road transportation sector. Understanding the unique impact of emissions from different vehicle types on O3 levels is crucial for developing targeted strategies for O3 pollution. This study applied the Community Multiscale Air Quality Modeling System (CMAQ) to comprehensively investigate the impacts of emissions from different vehicle types on O3 levels in various regions of Beijing and to provide valuable insights into source contributions and formation processes. The results revealed that various vehicle types exhibited different spatial-temporal emission patterns, with medium-heavy duty trucks (HDT) and mini-light passenger vehicles (LDPV) identified as the primary contributors to NOx (36.1 %) and VOC (57.6 %) emissions. Using the Integrated Source Apportionment Method (ISAM) coupled in CMAQ, we found the total vehicle emissions contributed to over 20 % of daily maximum 8-h average O3 (MDA8 O3) concentration, ranked as the second largest contributor after regional transport. Contributions to O3 formation from LDPV and medium-large passenger vehicles (MDPV) were 2.6-4.0 and 4.2-6.8 ppb and mainly concentrated in urban areas, while the contributions from mini-light duty trucks (LDT) and HDT were 3.5-4.8 and 3.7-6.2 ppb and mainly concentrated in suburban areas. Through scenario analysis that removed emissions from specific types of vehicles, we found removing LDPV emissions led to decreases in daytime O3 concentration by 0.3-3.8 ppb. In contrast, removing MDPV emissions led to notable O3 increases by 4.0-11.8 ppb at rush hours. Removing LDT and HDT emissions resulted in 0.6-8.0 ppb increases in nocturnal O3 concentrations while 0.8-2.0 ppb decreases during the afternoon. This research highlights the necessity of tailoring control strategies for different vehicle types to effectively reduce O3 levels in Beijing and provides useful information for decision-makers to formulate effective measures of vehicle management in the future.

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Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe3O4) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe3O4 self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.

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Whether maternal exposure to dust-sourced particulate matter (hereafter, dust PM2.5) is associated with stillbirth remains unknown. We adopted a sibling-matched case-control design to analyze 9332 stillbirths and 17,421 live births. We associated the risk of stillbirth simultaneously with dust and nondust components of PM2.5 and developed a nonlinear joint exposure-response function. Next, we estimated the burden of stillbirths attributable to the PM2.5 mixture. The concentration index was used to evaluate whether the burden of PM2.5-related stillbirths was disproportionally distributed among pregnancies exposed to dust-rich particles. Each 10 µg/m3 increase in dust PM2.5 was associated with a 14.5% (95% confidence interval: 5.5, 24.2%) increase in the odds of stillbirth. Based on the risk assessment across 137 countries, sand dust contributed to about 15% of the PM2.5 exposure but to about 45% of the PM2.5-related stillbirths during 2003-2019. In 2015, 30% of the PM2.5-related stillbirths were concentrated within 15% of pregnancies exposed to the dust-richest PM2.5. The index increased in subregions, such as South Asia, suggesting the growth of health inequality due to exposure to dust PM2.5. Based on our findings, land management, such as halting desertification, will help prevent stillbirths and reduce global maternal health inequality.

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Due to high humification, hyperthermophilic composting products (HP) show potential for remediating heavy metal pollution. However, the interaction between HP and heavy metals remains unclear. This study investigated the adsorption mechanism and soil remediation effect of HP on heavy metals. The results showed that the maximum adsorption capacity of HP increased by an average of 30.74 % compared to conventional composting products. HP transformed 34.87 % of copper, 42.55 % of zinc, and 35.63 % of lead from exchangeable and reducible forms into residual and oxidizable forms, thus reducing the soil risk level. In conclusion, HP significantly enhanced the adsorption of heavy metals and their transformation from unstable to stable forms, primarily due to the higher content of hydroxyl and carboxyl groups. This study aims to demonstrate the effectiveness of HP for remediating heavy metal pollution and to enhance the understanding of the underlying mechanism, which lays a foundation for waste utilization.

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Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

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Understanding the pollution situation of potentially toxic metals (PTMs) in fine road dust (FRD) in emerging industrialized cities and identifying priority control factors is crucial for urban environmental management, resident health protection, and pollution control. This study conducted a comprehensive investigation on PTMs pollution in FRD in Zunyi, a representative emerging industrialized city in the karst region of southwestern China. The average contents of Ni, Cr, Mn, Cu, Zn, Ba, Pb, V, and Co in the FRD were 43.2, 127.0, 1232.1, 134.4, 506.6, 597.8, 76.1, 86.8, and 16.2 mg kg-1, respectively, which were obviously higher than the corresponding background levels of the local soil except for V and Co. The comprehensive pollution level of the determined PTMs in the FRD was very high, primarily caused by Zn and Cu. The sources of PTMs in Zunyi FRD were traffic, industrial, construction, and natural sources, accounting for 38.0, 23.7, 21.9, and 16.4% of the total PTMs content, respectively. The PTMs in Zunyi FRD exhibited a low to moderate overall ecological risk level, mainly contributed by Cu and traffic source. The cancer risks of PTMs in Zunyi FRD were high for all populations. The non-carcinogenic risk of PTMs in Zunyi FRD was acceptable for adults, but cannot be ignored for children. According to the source-specific probabilistic health risk estimation results, the priority control source is industrial source and the priority control PTM is Cr. Local governments need to give more attention to the carcinogenic risks and health hazards posed by PTMs in the FRD.

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BACKGROUND: Exposure to air pollution has been associated with increased risks of cardiopulmonary diseases, cancer, and mortality, whereas residing near green spaces may reduce the risks. However, limited research explores their combined effect on oxidative stress. METHODS: A total of 251 participants with multi-time measurements were included in the longitudinal-designed study. Personal gaseous air pollutants (CO, NO, NO2, and O3,) and particulate pollution (PM1, PM2.5, and PM10) were measured and followed in two 7-day windows while ambient exposure levels and urine samples were collected simultaneously. Participants' Normalized Difference Vegetation Index (NDVI) was estimated and used to represent greenness exposure. Urinary oxidative stress biomarkers include free malondialdehyde (MDA), total MDA, and 8-hydroxydeoxyguanosine (8-OHdG). Linear mixed-effects models were used to independently and jointly estimate the associations of greenness and air pollution with oxidative stress biomarkers. RESULTS: We found consistent positive associations of personal ozone (O3) exposure with 8-OHdG percent changes, and this association was modified by gender and outdoor activity frequency. Consistent positive associations of personal lag 2-day carbon monoxide (CO) exposure with the percent changes of the three oxidative stress biomarkers were significant. We additionally observed that individuals who lived in greener areas had lower levels of urinary-free and total MDA. Participants in the highest NDVI tertile had 0.38 and 0.46 lower free and total MDA levels, [95 % CI: (-0.70, -0.05) and (-0.78, -0.13)], compared to the lowest NDVI tertile. There was also evidence indicating the modification effects by area, education, and outdoor activity frequency on associations between NDVI exposure and creatinine adjusted free MDA (all Pfor interaction < 0.05). Additional greenness modification effects on personal O3 exposure with urinary 8-OHdG was observed. CONCLUSION: Our study provides biological evidence of the modification effect of the built environment on the impact of air pollution.

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Purpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia. Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data. Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000). Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches. Clinical Trial Registration: ChiCTR2300073281.

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Exposure to polycyclic aromatic hydrocarbons (PAHs) in the Chinese population was among the highest globally and associated with various adverse effects. This study examines the impact of China's two-phase clean air initiatives, namely the Air Pollution Prevention and Control Action Plan (APPCAP) in 2013-2017 and the Blue-Sky Defense War (BSDW) in 2018-2020, on PAH levels and human exposures in Beijing. To evaluate the effects of APPCAP, we measured 16 PAHs in 287 PM2.5 samples collected in Beijing and 9 PAH metabolites in 358 urine samples obtained from 54 individuals who traveled from Los Angeles to Beijing between 2014 and 2018. The concentration of PM2.5-bound benzo[a]pyrene equivalents (BaPeq) decreased by 88.5% in 2014-2018 due to reduced traffic, coal, and biomass emissions. PAH metabolite concentrations in travelers' urine decreased by 52.3% in Beijing, correlated with changes in PM2.5 and NO2 levels. In contrast, no significant changes were observed in Los Angeles. To evaluate BSDW's effects, we collected 123 additional PM2.5 samples for PAH measurements in 2019-2021. We observed sustained reductions in BaPeq concentrations attributable to reductions in coal and biomass emissions during the BSDW phase, but those from traffic sources remained unchanged. After accounting for meteorological factors, China's two-phase clean air initiatives jointly reduced Beijing's PM2.5-bound BaPeq concentrations by 96.6% from 2014 to 2021. These findings provide compelling evidence for the effectiveness of China's clean air actions in mitigating population exposure to PAHs in Beijing.

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Rapid identification of drug mechanisms is vital to the development and effective use of chemotherapeutics. Herein, we develop a multichannel surface-enhanced Raman scattering (SERS) sensor array and apply deep learning approaches to realize the rapid identification of the mechanisms of various chemotherapeutic drugs. By implementing a series of self-assembled monolayers (SAMs) with varied molecular characteristics to promote heterogeneous physicochemical interactions at the interfaces, the sensor can generate diversified SERS signatures for directly high-dimensionality fingerprinting drug-induced molecular changes in cells. We further train the convolutional neural network model on the multidimensional SAM-modulated SERS data set and achieve a discriminatory accuracy toward 99%. We expect that such a platform will contribute to expanding the toolbox for drug screening and characterization and facilitate the drug development process.

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•Health benefits from China's pollution-carbon co-control actions have already been seen.•Co-control of air pollution and greenhouse gases can avoid premature deaths.•More comparative evaluations of the health impacts of specific policies are needed.

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The current study aimed to investigate the status of genes with prognostic DNA methylation sites in bladder cancer (BLCA). We obtained bulk transcriptome sequencing data, methylation data, and single-cell sequencing data of BLCA from public databases. Initially, Cox survival analysis was conducted for each methylation site, and genes with more than 10 methylation sites demonstrating prognostic significance were identified to form the BLCA prognostic methylation gene set. Subsequently, the intersection of marker genes associated with epithelial cells in single-cell sequencing analysis was obtained to acquire epithelial cell prognostic methylation genes. Utilizing ten machine learning algorithms for multiple combinations, we selected key genes (METRNL, SYT8, COL18A1, TAP1, MEST, AHNAK, RPP21, AKAP13, RNH1) based on the C-index from multiple validation sets. Single-factor and multi-factor Cox analyses were conducted incorporating clinical characteristics and model genes to identify independent prognostic factors (AHNAK, RNH1, TAP1, Age, and Stage) for constructing a Nomogram model, which was validated for its good diagnostic efficacy, prognostic prediction ability, and clinical decision-making benefits. Expression patterns of model genes varied among different clinical features. Seven immune cell infiltration prediction algorithms were used to assess the correlation between immune cell scores and Nomogram scores. Finally, drug sensitivity analysis of Nomogram model genes was conducted based on the CMap database, followed by molecular docking experiments. Our research offers a reference and theoretical basis for prognostic evaluation, drug selection, and understanding the impact of DNA methylation changes on the prognosis of BLCA.

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Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products.