Robust, Reproducible, and Scalable Synthesis of Silver Nanocubes.

It remains a challenge to accomplish colloidal synthesis of noble-metal nanocrystals marked by high quality, large quantity, and batch-to-batch consistency. Here we report a self-airtight setup for achieving robust, reproducible, and scalable production of Ag nanocubes with uniform and controlled sizes from 18-60 nm. Different from the conventional open-to-air setup, the self-airtight system makes it practical to stabilize the reaction condition by minimizing the loss of volatile reagents. The new setup also allows us to easily optimize the amount of O2 (from air) trapped in the system, ensuring burst nucleation of single-crystal seeds, followed by their slow growth into nanocubes. Most significantly, the new setup allows for the production of Ag nanocubes at gram quantities without sacrificing uniformity, corner/edge sharpness, controlled size, and high purity across different batches. The availability of high-quality Ag nanocubes in such a large quantity is anticipated to substantially boost their use in applications related to plasmonics, catalysis, and biomedicine.

Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow.

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Elevated unphosphorylated STAT1 and IRF9 in T and B cells of primary sjögren's syndrome: Novel biomarkers for disease activity and subsets.

OBJECTIVES: Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production and clinical manifestations remain unclear. More detailed studies hold promise for improved diagnostic methodologies and personalized treatment. METHODS: We analyzed peripheral blood T and B cell subsets from 34 pSS patients and 38 healthy donors (HDs) at baseline and upon stimulation regarding their expression levels of type I and II IFN signaling molecules (STAT1/2, IRF1, IRF9). Additionally, we investigated how the levels of these molecules correlated with serological and clinical characteristics and performed ROC analysis. RESULTS: Patients showed elevated IFN pathway molecules, including STAT1, STAT2 and IRF9 among most T and B cell subsets. We found a reduced ratio of phosphorylated STAT1 and STAT2 in patients in comparison to HDs, although B cells from patients were highly responsive by increased phosphorylation upon IFN stimulation. Correlation matrices showed further interrelations between STAT1, IRF1 and IRF9 in pSS. Levels of STAT1 and IRF9 in T and B cells correlated with the IFN type I marker Siglec-1 (CD169) on monocytes. High levels of STAT1 and IRF9 within pSS B cells were significantly associated with hypergammaglobulinemia as well as anti-SSA/anti-SSB autoantibodies. Elevated STAT1 levels were found in patients with extraglandular disease and could serve as a biomarker for this subgroup (p < 0.01). Notably, IRF9 levels in T and B cells correlated with EULAR Sjögren's syndrome disease activity index (ESSDAI). CONCLUSION: Here, we provide evidence that in active pSS patients, enhanced IFN signaling incl. unphosphorylated STAT1 and STAT2 with IRFs entertain chronic T and B cell activation. Furthermore, increased STAT1 levels candidate as biomarker of extraglandular disease, while IRF9 levels can serve as biomarker for disease activity.

China's carbon-neutral policies will reduce short-term PM2.5-associated excess incidence of cardiovascular diseases.

China's carbon-neutral target could have benefits for ambient fine particulate matter (PM2.5)-associated mortality. Although previous studies have researched such benefits, the potential impact on cardiovascular disease incidence burden is yet to be investigated thoroughly. Here, we first estimate the association between short-term PM2.5 exposure and the incidence of stroke and coronary heart disease (CHD) via a case-crossover study before projecting future changes in short-term PM2.5-associated excess incidence across China from 2025 to 2060 under three different emission scenarios. We find that, compared to the 2015-2020 baseline, average PM2.5 concentrations nationwide in 2060 under SSP119 (an approximation of a carbon-neutral scenario) are projected to decrease by 81.07%. The short-term PM2.5-related excess incidence of stroke and CHD is projected to be reduced to 3,352 cases (95% confidence interval: 939, 5,738)-compared with 34,485 cases under a medium-emissions scenario (SSP245)-and is expected to be accompanied by a 95% reduction in the related economic burden. China's carbon-neutral policies are likely to bring health benefits for cardiovascular disease by reducing short-term PM2.5-related incidence burden.

Putting Hybrid Nanomaterials to Work for Biomedical Applications.

Hybrid nanomaterials have found use in many biomedical applications. This article provides a comprehensive review of the principles, techniques, and recent advancements in the design and fabrication of hybrid nanomaterials for biomedicine. We begin with an introduction to the general concept of material hybridization, followed by a discussion of how this approach leads to materials with additional functionality and enhanced performance. We then highlight hybrid nanomaterials in the forms of nanostructures, nanocomposites, metal-organic frameworks, and biohybrids, including their fabrication methods. We also showcase the use of hybrid nanomaterials to advance biomedical engineering in the context of nanomedicine, regenerative medicine, diagnostics, theranostics, and biomanufacturing. Finally, we offer perspectives on challenges and opportunities.

Reactive Oxygen-Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing.

Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2 O2 ), resulting in decreased local pH and H2 O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2 O2 , leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

Spatiotemporal trends of hemorrhagic fever with renal syndrome (HFRS) in China under climate variation.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Multi-scroll attractor and its broken coexisting attractors in cyclic memristive neural network.

This paper proposes a simple-structured memristive neural network, which incorporates self-connections of memristor synapses alongside both unidirectional and bidirectional connections. Different from other multi-scroll chaotic systems, this network structure has a more concise three-neuron structure. This simple memristive neural network can generate a number of multi-scroll attractors in manageable quantities and shows the characteristics of the coexisting attractors and amplitude control. In particular, when the parameters are changed, the coexisting attractors break up around the center of gravity into two centrosymmetric chaotic attractors. Abundant dynamic behaviors are studied through phase portraits, bifurcation diagrams, Lyapunov exponents, and attraction basins. The feasibility of the system is demonstrated by building a circuit realization platform.

Single-Atom Catalysts for Selective Oxygen Reduction: Transition Metals in Uniform Carbon Nanospheres with High Loadings.

Transition metal single-atom catalysts (SACs) in uniform carbon nanospheres have gained tremendous interest as electrocatalysts owing to their low cost, high activity, and excellent selectivity. However, their preparation typically involves complicated multistep processes that are not practical for industrial use. Herein, we report a facile one-pot method to produce atomically isolated metal atoms with high loadings in uniform carbon nanospheres without any templates or postsynthesis modifications. Specifically, we use a chemical confinement strategy to suppress the formation of metal nanoparticles by introducing ethylenediaminetetraacetic acid (EDTA) as a molecular barrier to spatially isolate the metal atoms and thus generate SACs. To demonstrate the versatility of this synthetic method, we produced SACs from multiple transition metals, including Fe, Co, Cu, and Ni, with loadings as high as 3.87 wt %. Among these catalytic materials, the Fe-based SACs showed remarkable catalytic activity toward the oxygen reduction reaction (ORR), achieving an onset and half-wave potential of 1.00 and 0.831 VRHE, respectively, comparable to that of commercial 20 wt % Pt/C. Significantly, we were able to steer the ORR selectivity toward either energy generation or hydrogen peroxide production by simply changing the transition metal in the EDTA-based precursor.

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents.

Peritoneal metastatic cancer is a cancer caused by the direct growth of cancer cells from the primary site through the bloodstream, lymph, or peritoneum, which is a difficult part of current clinical treatment. In the abdominal cavity of patients with metastatic peritoneal cancer, there are usually nodules of various sizes and malignant ascites. Among them, nodules of different sizes can obstruct intestinal movement and form intestinal obstruction, while malignant ascites can cause abdominal distension and discomfort, and even cause patients to have difficulty in breathing. The pathology and physiology of peritoneal metastatic cancer are complex and not fully understood. The main hypothesis is "seed" and "soil"; i.e., cells from the primary tumor are shed and implanted in the peritoneal cavity (peritoneal metastasis). In the last two decades, the main treatment modalities used clinically are cytoreductive surgery (CRS), systemic chemotherapy, intraperitoneal chemotherapy, and combined treatment, all of which help to improve patient survival and quality of life (QOL). However, the small-molecule chemotherapeutic drugs used clinically still have problems such as rapid drug metabolism and systemic toxicity. With the rapid development of nanotechnology in recent years, therapeutic nanoagents for the treatment of peritoneal metastatic cancer have been gradually developed, which has improved the therapeutic effect and reduced the systemic toxicity of small-molecule chemotherapeutic drugs to a certain extent. In addition, nanomaterials have been developed not only as therapeutic agents but also as imaging agents to guide peritoneal tumor CRS. In this review, we describe the etiology and pathological features of peritoneal metastatic cancer, discuss in detail the clinical treatments that have been used for peritoneal metastatic cancer, and analyze the advantages and disadvantages of the different clinical treatments and the QOL of the treated patients, followed by a discussion focusing on the progress, obstacles, and challenges in the use of therapeutic nanoagents in peritoneal metastatic cancer. Finally, therapeutic nanoagents and therapeutic tools that may be used in the future for the treatment of peritoneal metastatic cancer are prospected.

Staminal hairs increase pollinator attraction and pollination accuracy in Tradescantia fluminensis (Commelinaceae).

Staminal hairs are the particular appendages of stamens, which may affect pollinator foraging behaviour and pollen transfer. However, experimental evidence of the functions of staminal hairs in pollination remains scarce. Here, we conducted staminal hair manipulation experiments in Tradescantia fluminensis (Commelinaceae) to investigate their effects on visitation and pollen transfer by bees. Our observations revealed that both visitation rates and visit duration of honeybees (Apis cerana) to control flowers were significantly higher than that of hairless flowers. Moreover, removing the staminal hairs significantly decreased pollen deposition by honeybees (A. cerana), but did not affect pollen removal. The staminal hair was similar in length to the stamen and the pistil of T. fluminensis. The staminal hairs provide more footholds for honeybees, and they lay prone on the staminal hairs to collect pollen, which increased the accuracy of pollination through the consistent pollen placement and pick-up on the ventral surface of honeybees. These results showed that the staminal hairs in T. fluminensis may represent an adaptation to attract pollinators and enhance pollination accuracy.

Projecting future labor losses due to heat stress in China under climate change scenarios.

Climate change is expected to increase occupational heat stress, which will lead to diminished work performance and labor losses worldwide. However, sub-regional analyses remain insufficient, especially for countries with a heterogeneous spatial distribution of working populations, industries and climates. Here, we projected heat-induced labor losses in China, by considering local climate simulations, working population characteristics and developing an exposure-response function suitable for Chinese workers. We showed that the annual heat-induced work hours lost (WHL), compared to the baseline of 21.3 billion hours, will increase by 121.1% (111.2%-131.1%), 10.8% (8.3%-15.3%), and -17.8% (-15.3%--20.3%) by the end of the century under RCP(Representative Concentration Pathways)8.5, RCP4.5, and RCP2.6, respectively. We observed an approximately linear upward trend of WHL under RCP8.5, despite the decrease in future working population. Notably, WHL will be most prominent in the southern, eastern and central regions, with Guangdong and Henan accounting for a quarter of national total losses; this is largely due to their higher temperature exposure, larger population size, and higher shares of vulnerable population in total employment. In addition, limiting global warming to 1.5 °C would yield substantial gains. Compared to RCP2.6, RCP4.5, and RCP8.5, all provinces can avoid an average of 11.8%, 33.7%, and 53.9% of annual WHL if the 1.5 °C target is achieved, which is equivalent to avoiding 0.1%, 0.6%, and 1.4% of annual GDP losses in China, respectively. This study revealed climate change will exacerbate future labor losses, and adverse impacts can be minimized by adopting stringent mitigation policies coupled with effective adaptation measures. Policymakers in each province should tailor occupation health protection measures to their circumstances.

Projections of mortality risk attributable to short-term exposure to landscape fire smoke in China, 2021-2100: a health impact assessment study.

BACKGROUND: Landscape fire smoke, including smoke from all vegetation burning in natural and cultural landscapes, remains a threat to the health of the population. However, the future health impacts of landscape fire smoke in China have not been sufficiently investigated. We aimed to estimate the mortality risk attributable to landscape fire-related PM2·5 under different scenarios. METHODS: In this health impact assessment study, we used the projected population and landscape fire-related PM2·5 concentration to calculate deaths attributable to short-term exposure to landscape fire smoke PM2·5 during 2021-2100. We did the analysis in three defined future periods: 2021-40 (near term), 2051-70 (medium term), and 2081-2100 (long term), with 1986-2005 as the historical period. We used fire-specific short-term epidemiological functions with the regional parameters specific to China. We assessed the mortality risks of landscape fire-related smoke and further identified their spatiotemporal distribution under two shared socioeconomic pathway (SSP) scenarios: SSP1-2·6, an optimistic scenario with strict control of carbon emissions, and SSP2-4·5, an intermediate scenario with weaker control of carbon emissions. FINDINGS: The national mortality rate attributable to short-term exposure (ie, a few days) to landscape fire-related PM2·5 is projected to increase compared with historical values. The national deaths attributable to landscape fire smoke PM2·5 could peak in 2021-40, with increases of 28·10% (95% CI 14·08-53·11) under the SSP1-2·6 scenario and 37·38% (14·08-53·11) under the SSP2-4·5 scenario. Deaths would then decrease slightly during 2051-70 and 2081-2100. The provinces with the highest projected number of deaths attributable to landscape fire-related PM2·5 are located in east and south-central China, and those with the largest percentage increase in projected deaths are located in northwest and southwest China. INTERPRETATION: Our results suggest that global warming could increase the contribution of landscape fire smoke to the total PM2·5 concentration, leading to an increase in the mortality rate in China. Our findings could help policy makers implement effective interventions in hotspot areas during different periods to reduce the impact of landscape fire smoke on human health. FUNDING: The National Natural Science Foundation of China, National Key Research and Development Program of China, and the Wellcome Trust.

Genomic insights into biased allele loss and increased gene numbers after genome duplication in autotetraploid Cyclocarya paliurus.

BACKGROUND: Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual. RESULTS: Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture. CONCLUSIONS: Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.

Advances of phytotherapy in ischemic stroke targeting PI3K/Akt signaling.

The pathogenesis of ischemic stroke is complex, and PI3K/Akt signaling is considered to play a crucial role in it. The PI3K/Akt pathway regulates inflammation, oxidative stress, apoptosis, autophagy, and vascular endothelial homeostasis after cerebral ischemia; therefore, drug research targeting the PI3K/Akt pathway has become the focus of scientists. In this review, we analyzed the research reports of antiischemic stroke drugs targeting the PI3K/Akt pathway in the past two decades. Because of the rich sources of natural products, increasing studies have explored the value of natural compounds, including Flavonoids, Quinones, Alkaloids, Phenylpropanoids, Phenols, Saponins, and Terpenoids, in alleviating neurological impairment and achieved satisfactory results. Herbal extracts and medicinal formulas have been applied in the treatment of ischemic stroke for thousands of years in East Asian countries. These precious clinical experiences provide a new avenue for research of antiischemic stroke drugs. Finally, we summarize and discuss the characteristics and shortcomings of the current research and put forward prospects for further in-depth exploration.