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Chemoresistance remains a principal culprit for the treatment failure in colorectal cancer (CRC), especially for patients with recurrent or metastatic disease. Deciphering the molecular basis of chemoresistance may lead to novel therapeutic strategies for this fatal disease. Here, UBR5, an E3 ubiquitin ligase frequently overexpressed in human CRC, is demonstrated to mediate chemoresistance principally by inhibiting ferroptosis. Paradoxically, UBR5 shields oxaliplatin-activated Smad3 from proteasome-dependent degradation via Lys 11-linked polyubiquitination. This novel chemical modification of Smad3 facilitates the transcriptional repression of ATF3, induction of SLC7A11 and inhibition of ferroptosis, contributing to chemoresistance. Consequently, targeting UBR5 in combination with a ferroptosis inducer synergistically sensitizes CRC to oxaliplatin-induced cell death and control of tumor growth. This study reveals, for the first time, a major clinically relevant chemoresistance mechanism in CRC mediated by UBR5 in sustaining TGFβ-Smad3 signaling and tuning ferroptosis, unveiling its potential as a viable therapeutic target for chemosensitization.

Background: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. Methods: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. Results: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (β = −127.7 h per month, standard error = 25.83, P

Constructed wetland systems have been widely used in China due to their advantages of good treatment effect, low cost and environmental friendliness. However, traditional constructed wetlands have challenges in application such as deactivation due to filler clogging, difficulty in filler replacement and low adaptability. To address the above problems, this research proposes a modular filler design constructed wetland based on the concept of assembly construction, which can quickly replace the clogged filler without destroying the overall structure of the wetland. Four commonly used fillers were selected and applied to the pilot system of the assembled constructed wetland in this study, in order to investigate the purification effect of the constructed wetland system with different filler module combinations (CW1, CW2, CW3) on the simulated wastewater. The results showed that the filler combination CW1 was the best for the removal of NH4+-N, and for TP and COD, CW2 has the best removal effect. Therefore, the assembled constructed wetland is adjustable and substantially reduces the maintenance cost, which provides technical guidance for its application in engineering. HIGHLIGHTS Proposed a pilot system for the prefabricated constructed wetland.; Explored the purification effects of different combinations of fillers.; Analyzed concentration changes of pollutants along the route.; Conducted cost analysis for replacing fill in two types of wetlands.;

To investigate the effects of chitosan and ε-polylysine on the cell structure and cytoprotective enzymes of Carbibacterium divergens to explore their inhibition mechanism against Carbibacterium divergens, the broth dilution method was used to determine the minimum inhibitory concentrations (MICs) of chitosan and ε-polylysine against Carbibacterium divergens. Their effects on the cellular structure of Carbibacterium divergens were then assessed by several indexes, such as growth curves, electronic conductivity, extracellular nucleic acids, extracellular proteins, and alkaline phosphatase (AKP) activity, and the microstructure of bacteria were also observed by scanning electron microscopy (SEM). In addition, their role in oxidative stress was analyzed by detecting changes in catalase (CAT) activity and superoxide dismutase (SOD) activity. The results showed that the MIC of chitosan and ε-polylysine against Carbibacterium divergens was 0.1953 and 0.1563 mg/mL, respectively. The intracellular components (AKP, proteins, nucleic acids, and ions) leaked after treatment with MIC and 2MIC chitosan and ε-polylysine. The mass concentrations of chitosan and ε-polylysine were negatively correlated with enzyme activity, and the activities CAT and SOD significantly decreased (P

KRAS-TP53 co-mutation is strongly associated with poor prognosis and high malignancy in gastrointestinal cancers. Therefore, a novel approach to oncotherapy may lie in combination therapy targeting both KRAS and TP53. Herein, we present a novel self-assembled nanoparticle (HA-TPP/A) that are functionalized nano-carrier hyaluronic acid (HA)-TPP conjugate (HA-TPP) to degrade mutant p53 proteins (mutp53) and co-deliver AMG510 for treating KRAS-TP53 co-alteration of gastrointestinal cancers by inhibiting the mutant KRAS and mutp53 signaling pathways. The HA-TPP/A nanoparticles led to ubiquitination-dependent proteasomal degradation of mutp53 by targeting damage to mitochondria. Furthermore, these nanoparticles abrogated the gain-of-function (GOF) phenotypes of mutp53 and increased sensitivity to AMG510-induced cell killing, thereby reducing cell proliferation and migration in gastrointestinal cancer with KRAS-TP53 co-mutation. The co-loaded HA-TPP/A nanoparticles demonstrated remarkable therapeutic efficacy in a tumor-bearing mouse model, particularly in KRAS-TP53 double mutant expressing cancer cells, compared with single drug and combined free drug groups. Notably, HA-TPP/A is the first reported nanoparticle with an ability to co-target KRAS-TP53, providing a promising approach for therapy in highly malignant gastrointestinal tumors and potentially expanding clinical indications for AMG510 targeted therapies in gastrointestinal tumors.

ObjectiveBoth camrelizumab plus paclitaxel and carboplatin (CTC) and sintilimab plus gemcitabine and cisplatin or carboplatin (SGP) have been approved by the National Medical Products Administration of China (NMPA) for the first-line treatment of local advanced or metastatic sqNSCLC. However, the comparison of the two treatments as first-line treatments in efficacy or pharmacoeconomics has barely been studied. To deeply understand the costs and outcomes of the two treatments, this work directly compared the cost-effectiveness for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.MethodsA network meta-analysis was first performed based on the three clinical trials, namely, CameL-Sq, ORIENT-12, and C-TONG1002, to compare the clinical benefits of the two treatments. The Weibull approximation was applied to further calculate the life expectancy of the two treatments. The partitioned survival model (PSM) was next established, and one-way sensitivity analysis and probabilistic sensitivity analysis were also performed to evaluate the stability of the underlying parameter values and assumptions within the model.ResultsCTC treatment gained 0.68 QALYs and cost $14,764. SGP treatment gained 0.54 QALYs and cost $14,584. The CTC arm gained 0.14 additional QALYs and cost $179 more than the SGP arm, and the ICERs was $1,269/QALY, which was lower than one-fold GDP per capita in the Chinese mainland ($12,734 GDP per capita in 2022). In probabilistic sensitivity analysis, when the WTP ranged from $12,734–38,202 (1–3 folds, 2022 GDP per capita in China), the CTC group had higher probabilities than the SGP group for being cost effective, which ranged from 85.65% to 88.38%.ConclusionFrom the perspective of the payers, camrelizumab plus chemotherapy was cost-effective compared with sintilimab plus chemotherapy for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.

Highlights An efficient moist-electric generator with ultra-fast electric response to moisture is achieved by triggering Grotthuss protons hopping in the moisture-electric–moisture-sensitive heterostructure. The moist-electric generator produces a quick response (0.435 s), an unprecedented ultra-fast response rate of 972.4 mV s−1 to alternating moisture stimulation and stable output for 8 h. An obstructive sleep apnea hypoventilation syndrome diagnostic system based on a moist-electric generator was developed to monitor hypopnea and apnea in real time and successfully diagnose them with early warning.

Background: High-grade serous ovarian carcinoma (HGSOC) is a pathologic subtype of ovarian cancer (OC) with a more lethal prognosis. Extensive heterogeneity results in HGSOC being more susceptible to treatment resistance and adverse treatment effects. Revealing the heterogeneity involved is crucial. Methods: We downloaded the single-cell RNA-seq (scRNA) data from GEO database and performed a scRNA analysis for cell landscape of HGSOC by using the Seurat package. The highly expressed genes were uploaded into the DAVID and KEGG database for enrichment analysis, and the AUCell package was used to calculate cancer-associated hallmark score. The SCENIC analysis was used for key regulons, the estrogen response enrichment scores in TCGA-OV RNA-seq dataset were calculated by using the GSVA package. Besides, the expression of STRA6 and IRF1 and the cell invasion and migration in si-STRA6 OC cells were detected by using the quantitative reverse transcription (qRT)-PCR method and Transwell assay respectively. Results: We successfully constructed a single-cell atlas of HGSOC and delineated the heterogeneity of epithelial cells therein. There were five epithelial cell subpopulations, GLDC + Epithelial cells, PEG3+ leydig cells, STRA6+ granulosa cells, POLE2+ Epithelial cells, and AURKA + Epithelial cells. STRA6+ granulosa cells have the potential to promote tumor growth as well as the highest estrogen response early activity through the biological pathways analysis of highly expressed genes and estrogen response score of ssGSEA. We found that IRF1 and STRA6 expression was remarkably upregulated in the OC cancer cell line HEY. Silencing of STRA6 markedly decreased the invasion and migration ability of the OC cancer cell line HEY. Conclusion: There is extreme heterogeneity of epithelial cells in HGSOC, and STRA6+ granulosa cells may be able to promote cancer progression. Our findings are benefit to the heterogeneity identification of HGSOC and develop targeted therapy strategy for HGSOC patients.

ABSTRACTTerrestrial plants can influence the growth and health of adjacent plants through interspecific interaction. Here, the mechanisms of interspecific plant interaction on microbial function and nutrient utilization in the plant-soil interface (non-rhizosphere soil, rhizosphere soil, and root) were studied by soybean- and potato-poplar intercropping. First, metagenomics showed that soybean- and potato-poplar intercropping influenced the composition and co-occurrence networks of microbial communities in different ecological niches, with higher stability of the microbial community in soybean intercropping. Second, the gene abundance related to carbon metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling was increased at the poplar-soil interface in soybean intercropping. Moreover, soybean intercropping increased soil nutrient content and enzymatic activity. It showed higher metabolic potential in nutrient metabolism and transportation. Third, functional microorganisms that influenced nutrient cycling and transportation in different intercropping have been identified, namely Acidobacteria, Sphingomonas, Gemmatimonadaceae, Alphaproteobacteria, and Bradyrhizobium. Therefore, intercropping can construct microbial communities to alter metabolic functions and improve nutrient cycling and absorption. Interspecific plant interactions to influence the microbiome were revealed, opening up a new way for the precise regulation of plant microbiome.IMPORTANCEPoplar has the characteristics of wide distribution, strong adaptability, and fast growth, which is an ideal tree species for timber forest. In this study, metagenomics and elemental analysis were used to comprehensively reveal the effects of interspecific plant interactions on microbial communities and functions in different ecological niches. It can provide a theoretical basis for the development and application of the precise management model in poplar.

Introduction: The clinicopathological features of segmental membranous glomerulopathy (SMGN) have not been well characterized. The aim of this study was to investigate the prevalence and clinicopathological features of SMGN in adults. Methods: Adult patients with biopsy-confirmed SMGN in the native kidney at our center between January 2017 to September 2020 were identified. The clinicopathological features of SMGN were collected. The glomerular deposition of IgG subclasses, M-type phospholipase A2 receptor 1 (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), and neural epidermal growth factor-like 1 protein (NELL1) were tested. Clinical and pathologic features were comparable between NELL1-positive and NELL1-negative SMGN. Results: A total of 167 patients with biopsy-proven SMGN were enrolled. During the same period, 32,640 (33.0%) out of 98,939 renal biopsies were diagnosed with membranous nephropathy (MN) in adults. SMGN accounted for 0.17% of total kidney biopsies and 0.51% of MN in adults. One hundred and fifty (89.8%) cases were isolated SMGN, and 17 (10.2%) cases were complicated with other kidney disease. Clinically, the median age of isolated SMGN patients was 41.5 years, with female (74%) predominance, and 33.1% had full nephrotic syndrome. Pathologically, IgG1 was the dominant subclass (92.5%), followed by IgG4 (45.0%). PLA2R and THSD7A staining were done in 142 and 136 isolated SMGN cases, respectively, in which, all the cases showed negative. NELL1 staining was done in 135 isolated SMGN cases; 58 cases (43.0%) showed positive. Fifty-eight patients (41.1%) had diffuse (≥90%) foot process effacement, and 119 patients (83.8%) had either stage I (38.0%) or stage II (45.8%) membranous alterations in patients with SMGN. Most patients with NELL1-positive SMGN were female. Patients with NELL1-positive SMGN were more likely with lower prevalence of full nephrotic syndrome than NELL1-negative SMGN. Conclusions: SMGN is a relatively rare pathological type. Majority of patients with isolated SMGN were female, with a median age of 41.5 years, 33.1% had full nephrotic syndrome, absence of PLA2R and THSD7A, 43.0% with NELL1-positive, and mainly stage I or II MN (83.8%). NELL1 is the major target antigen of SMGN in adults.

Abstract Bilayer graphene (BLG) is intriguing for its unique properties and potential applications in electronics, photonics, and mechanics. However, the chemical vapor deposition synthesis of large-area high-quality bilayer graphene on Cu is suffering from a low growth rate and limited bilayer coverage. Herein, we demonstrate the fast synthesis of meter-sized bilayer graphene film on commercial polycrystalline Cu foils by introducing trace CO2 during high-temperature growth. Continuous bilayer graphene with a high ratio of AB-stacking structure can be obtained within 20 min, which exhibits enhanced mechanical strength, uniform transmittance, and low sheet resistance in large area. Moreover, 96 and 100% AB-stacking structures were achieved in bilayer graphene grown on single-crystal Cu(111) foil and ultraflat single-crystal Cu(111)/sapphire substrates, respectively. The AB-stacking bilayer graphene exhibits tunable bandgap and performs well in photodetection. This work provides important insights into the growth mechanism and the mass production of large-area high-quality BLG on Cu.

Abstract The cytidine deaminase, Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B, herein termed A3B), is a critical mutation driver that induces genomic instability in cancer by catalyzing cytosine-to-thymine (C-to-T) conversion and promoting replication stress (RS). However, the detailed function of A3B in RS is not fully determined and it is not known whether the mechanism of A3B action can be exploited for cancer therapy. Here, we conducted an immunoprecipitation-mass spectrometry (IP-MS) study and identified A3B to be a novel binding component of R-loops, which are RNA:DNA hybrid structures. Mechanistically, overexpression of A3B exacerbated RS by promoting R-loop formation and altering the distribution of R-loops in the genome. This was rescued by the R-loop gatekeeper, Ribonuclease H1 (RNASEH1, herein termed RNH1). In addition, a high level of A3B conferred sensitivity to ATR/Chk1 inhibitors (ATRi/Chk1i) in melanoma cells, which was dependent on R-loop status. Together, our results provide novel insights into the mechanistic link between A3B and R-loops in the promotion of RS in cancer. This will inform the development of markers to predict the response of patients to ATRi/Chk1i.

Abstract Chronic kidney disease (CKD) and heart failure (HF) are highly prevalent, aggravate each other, and account for substantial mortality. However, the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain limited. Here, we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ (SFO) and thereby to paraventricular nucleus (PVN) and rostral ventrolateral medulla that modulates sympathetic outflow. This kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each model. Interruption of the pathway by kidney deafferentation, selective deletion of angiotensin II type 1a receptor (AT1a) in SFO, or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and HF. Thus, kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both organs. These results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease conditions. This suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.

Paeonia suffruticosa is widely cultivated globally due to its medicinal and ornamental value. Peony pollen (PP) is commonly used in Chinese folk medicine to make tea to treat benign prostatic hyperplasia (BPH), but its molecular mechanism against BPH is yet to be comprehended. The objective of this research was to experimentally verify the effect of PP in the treatment of BPH and to preliminarily reveal its mechanism of action on BPH using network pharmacology methods. The results revealed that PP could decrease prostate volume and prostate index, serum testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) levels. Moreover, it could improve prostate tissue structure in BPH model animals as well. Additionally, database searches and disease target matching revealed 81 compounds in PP. Of these, 3, 7, 8, 2′-tetrahydroxyflavone, Chrysin, Wogonin, Limocitrin, and Sexangularetin were the top five compounds associated with the therapeutic effects of BPH. Furthermore, 177 therapeutic targets for BPH were retrieved from databases of Swiss Target, DisGeNET, Drugbank, Genecards, OMIM, TTD, and Uniprot. In contrast, core targets AKT1, EGFR, IL6, TNF, and VEGFA were obtained by PPI network diagram. Molecular docking also showed that the main efficacy components and potential core targets in PP had good binding capacity. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis established that the effect of PP in BPH therapy was mainly through regulating the expression levels of protein kinase B on phosphatidylinositol 3-kinase and phosphatidylinositol 3-kinase-protein kinase B pathways. Additionally, Western blot experiments also exhibited a significant elevation in the activated PI3K and AKT proteins in the model (Mod) group relative to the control (Con) group, and the expression of these activated proteins was significantly reduced after PP administration. In summary, this research provides a scientific basis for employing PP to treat BPH, preliminarily reveals its mechanism of action and potential targets, and lays the foundation for further research and development.

This study aimed to investigate the anti-inflammatory effect of walnut-derived peptide LPLLR (LP-5) in oxidative stress-induced Caco-2 cells and model mice. The results showed that LP-5 significantly increased the activities of CAT and SOD, while decreased the levels of MDA both in vitro and in vivo. The oxidative stress signaling was regulated by promoting Nrf2 nuclear transfer, up-regulating HO-1 expression, and down-regulating Keap1 expression. As demonstrated by molecular docking, LP-5 could effectively bind Keap1. Additionally, LP-5 effectively inhibited the activation of the NLRP3 inflammasome via down-regulating the expression of NLRP3, ASC, and caspase-1, significantly reducing the release of inflammatory cytokines, including IL-18, IL-1β, and TNF-α, thereby preventing cell apoptosis. Moreover, LP-5 increased the production of IL-10 and decreased the levels of iNOS and COX-2 in Caco-2 cells. These data suggested that LP-5 ameliorated oxidative stress-mediated inflammation by inhibiting the NLRP3 inflammasome by activating Nrf2/Keap1 signaling.

Highlights Large-area production of self-standing graphene nanofilm (~ 20 cm) through a clean ‘substrate replacement’ strategy. Realizing highly crystalline graphene nanofilms without micro-gasbags by introducing polymers. The graphene nanofilms demonstrate a solid light–matter interaction (photoelectric conversion in the mid-infrared and electromagnetic interference (EMI) shielding in X-band) with performance beyond state-of-the-art graphene/silicon diodes and EMI materials.

This study aimed to investigate the relationship between ZNF582 promoter methylation (ZNF582m) level and radiosensitivity of cervical cancer and its biological basis. This was a prospective multicenter clinical study, comprising two independent cohorts of locally advanced cervical cancer patients. Exfoliated cervical cells were collected at 0, 24, 30, 36, 48, and 64 Gy to test ZNF582m levels. Radiotherapy response was evaluated according to RECIST Version. RT-PCR and WT were used to detect the mRNA and protein expression levels; MTT and flow cytometry were used to detect the cell viability and cell cycle, respectively. While clone formation and subcutaneous tumorigenesis in nude mice were used to detect the growth of HeLa cells with/without ZNF582 overexpression. In the first cohort, 22 cases achieved complete remission (CR) or partial response (PR), and the other 28 cases exhibited stable disease (SD). Radiotherapy reduced ZNF582m levels among all patients. Initial lever of ZNF582m was significantly higher in the Responder (CR + PR) group than in the SD group. Also, patients with higher initial lever ZNF582m were more sensitive towards radiotherapy than ZNF582m-low patients. The second cohort confirmed the above results. The amplitude of ZNF582m levels were related to the radiotherapeutic response; some patients of ZNF582m-low showed a transient increase in ZNF582m, and present greater radiosensitivity than other ZNF582m-low patients. In vitro, ZNF582 protein overexpression promoted cell cycle arrest in S phase. These results suggested that higher ZNF582m levels predicted greater radiosensitivity in clinical cervical cancer cases. Overexpressed ZNF582 conferred radioresistance by cell cycle arrest in vitro.

Introduction Preeclampsia (PE) is a serious pregnancy syndrome. Advanced maternal age (≥ 35 years old) is one of the major risk factors of PE and placental aging is considered to be related to this disease. However, the mechanisms underlying these phenomena remain obscured. Methods Gene expression profiles of PE and non-PE placental samples were curated from the GSE75010 dataset. A diagnostic model was constructed and immune characteristics of PE subtypes were estimated. Results A total of 58 aging-related genes, which may be associated with PE, were identified. Among them, LEP and FLT1 may be key aging-related genes. Based on 5 top genes (PIK3CB, FLT1, LEP, PIK3R1, CSNK1E), a diagnostic nomogram for PE was built (AUC = 0.872 in the GSE75010 dataset). Three molecular subtypes were clustered, which had different immune and angiogenesis characteristics. Conclusion The present study suggests the potential implications of aging-related genes in diagnosing PE. Diverse immune characteristics may be involved in the placental aging of PE.

Abstract Autophagy, a highly conserved degradation process of eukaryotic cells, has been proven to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anticancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.

Abstract Background Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility. Results Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo. Conclusion In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.

Abstract Background The catastrophic health expenditure of older adults results in serious consequences; however, the issue of whether cognitive status and living situations contribute to such financial burdens is uncertain. Our aim was to compare the differences in catastrophic health expenditure between adults living alone with cognitive impairment and those adults living with others and with normal cognition. Methods We identified 909 observations of participants living alone with cognitive impairment (cases) and 37,432 observations of participants living with others and with normal cognition (comparators) from the 2011/2012, 2013, 2015 and 2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We used propensity score matching (1:2) to create matched cases and comparators in a covariate-adjusted logistic regression analysis. Catastrophic health expenditure was defined as an out-of-pocket cost for health care ≥40% of a household’s capacity to pay. Results In comparison with participants living with others and with normal cognition, those adults living alone with cognitive impairment reported a higher percentage of catastrophic health expenditure (19.5% vs. 11.8%, respectively, P

The title compound, C13H10ClNO2, was synthesized by a Buchwald–Hartwig reaction and its crystal structure was investigated for the first time. Crystallization in a variety of solvents led to the discovery of one crystal form. High-quality single crystals were obtained by slow evaporation and the crystal structure was determined by single-crystal X-ray diffraction. The molecules in the crystal structures are highly twisted [the dihedral angle between the aromatic rings is 34.66 (6)°] and pair up to form acid–acid dimers.

Antimicrobials are extensively utilized in dairy farms to prevent and control diseases in cattle. However, their use contributes to the emergence of antimicrobial-resistant bacteria (ARB) and antimicrobial-resistant genes (ARG), and these can be transmitted to the environment. Regular monitoring of antimicrobial resistance (AMR) is crucial for implementing effective mitigation strategies. This research aimed to assess the environmental microbial species present on dairy farms in Shandong Province and characterize the antimicrobial resistance profiles of the isolates. Five dairy farms located in Shandong Province were selected, representing the prevalent large-scale farming patterns in the area. Sampling took place from April to June 2022, with a total of 223 isolates collected from various environmental locations within each farm (bedding, sports field, and milking parlor). Matrix-assisted laser desorption/ionization—time-of-flight mass spectrometry (MALDI-TOF MS) was employed to identify the species of the clinical isolates. The main pathogens isolated were Aerococcus viridans (5.38%, n = 12), Corynebacterium xerosis (4.93%, n = 11), and Acinetobacter lwoffii (4.03%, n = 9). Among the bacterial isolates, resistance to lincomycin was highest at 91%, and 88% were resistant to sulfadiazine. Antimicrobial resistance genes were detected in only a small proportion of the isolates, the most common of which was sul1. These findings highlight the necessity for careful evaluation of antimicrobial usage in maintaining their effectiveness in human medicine. Understanding the microbial species present and their antimicrobial resistance profiles aids in focusing efforts toward sustainable antimicrobial use and safeguarding human health.

TGF-β/Smad signaling plays a vital role in the development of fibrosis in diabetic kidney disease (DKD). However, remedies targeting key elements in TGF-β/Smad signaling are lacking. Here, we found that TGF-β receptor 1 (TGFBR1), a key protein in TGF-β/Smad signaling, was upregulated in kidney from diabetic mice and patients with DKD. Induction of TGFBR1 was regulated by microRNA-10a and -10b (miR-10a/b) by a post-transcriptional mechanism. Furthermore, the decreased XRN2, an exoribonuclease, was identified to contribute to affecting miR-10a/b maturation in vitro. In streptozotocin (STZ)-induced DKD mice, preventing the reduction of miR-10a/b in the kidney by an in situ lentivirus-injection method attenuated collagen deposition and foot process effacement, whereas deprivation of miR-10a/b aggravated renal fibrosis. Mechanistically, manipulating miR-10a/b in the kidney influenced TGFBR1 protein expression, TGF-β/Smad signaling activation, and downstream pro-fibrotic genes expression including fibronectin (FN) and α-smooth muscle actin (α-SMA). In a cohort of patients diagnosed DKD, renal miR-10a/b expressions were downregulated, whereas both TGFBR1 and fibrosis were enhanced. Our finding suggests that overexpressing miR-10a/b in kidney may be a promising method for the treatment of fibrosis in DKD.

The pitting corrosion behavior of AZ91 alloy before and after micro-oxidation treatment in 3.5% NaCl solution was investigated by cyclic potentiodynamic polarization (CPDP) and optical and SEM observations of corroded surfaces at different polarization potentials. The CPDP results show that both the alloy and the MAO-coated alloy suffer from pitting corrosion and it is difficult for pits to stop growth once the pits initiates. It is revealed that the air-formed MgO film on AZ91 alloy, the MAO coating along with corrosion products (mainly Mg(OH)2) formed during CPDP can significantly influence the kinetics of the redox reactions of Mg, and further influence the propagation behavior of pitting corrosion. The optical and SEM images show that the corrosion products on AZ91 alloy are dense and protective but on the MAO-coated corrosion products are very loose. Such observations support the analyses of CPDP results that pits on AZ91 alloy spread to the width whereas pits on MAO-coated alloy propagate to the depth. Overall, pitting corrosion on the MAO-coated alloy can be very severe once the coating ruptures and post-treatments are necessary to provide a promising corrosion protection for the Mg alloys.

ObjectiveEvidence of spatial disparity in dementia mortality in China has been found to have higher dementia mortality in eastern and rural China. Regional factors of physical and social features may be influencing this spatial disparity. However, the extent of spatial difference in dementia mortality across small regional localities is unclear. This study aims to investigate the geographic variations in mortality and risk of all dementia subtypes and identify the effect of the associated environmental risk factors.MethodsWe used surveillance data on death reports from Alzheimer’s disease and other forms of dementia in Zhejiang province from 2015 to 2019. We estimated the relative risk of dementia mortality using a Bayesian spatial model. We mapped predicted relative risk to visualize the risk of death from different types of dementia and to identify risk factors associated with dementia.ResultsThirty thousand three hundred and ninety-eight deaths attributable to dementia as the underlying or related cause (multiple causes) were reported during 2015–2019. Counties and districts in the southeast and west of Zhejiang province had significantly higher standardized mortality ratios than others. Counties and districts with a smaller proportion of residents aged 60 years or older, poorer economic status, insufficient health resources, and worse pollution had a higher risk of deaths due to dementia.ConclusionHigher risks of dementia mortality were found in counties and districts with poorer economic status, insufficient health resources, and worse pollution in Zhejiang. Our study adds new evidence on the association between socioeconomic and environmental factors and the mortality risk due to dementia.

Abstract Background Aging metrics incorporating cognitive and physical function are not fully understood, hampering their utility in research and clinical practice. This study aimed to determine the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function and the associations of the three metrics with mortality. Methods We considered three existing aging metrics including the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them using data from the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazards regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. Results In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2, 16.6, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR) (95% confidence interval (CI)) 2.87 (1.74–4.74); FI, OR (95% CI) 1.94 (1.50–2.50); MCR, OR (95% CI) 1.27 (1.00–1.62)). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement and continuous net reclassification improvement (all P

The complement pathway is a major component of the innate immune system, which is critical for recognizing and clearing pathogens that rapidly react to defend the body against external pathogens. Many components of this pathway are expressed throughout the brain and play a beneficial role in synaptic pruning in the developing central nervous system (CNS). However, excessive complement-mediated synaptic pruning in the aging or injured brain may play a contributing role in a wide range of neurodegenerative diseases. Complement Component 1q (C1q), an initiating recognition molecule of the classical complement pathway, can interact with a variety of ligands and perform a range of functions in physiological and pathophysiological conditions of the CNS. This review considers the function and immunomodulatory mechanisms of C1q; the emerging role of C1q on synaptic pruning in developing, aging, or pathological CNS; the relevance of C1q; the complement pathway to neurodegenerative diseases; and, finally, it summarizes the foods with beneficial effects in neurodegenerative diseases via C1q and complement pathway and highlights the need for further research to clarify these roles. This paper aims to provide references for the subsequent study of food functions related to C1q, complement, neurodegenerative diseases, and human health.

Formaldehyde (HCHO) plays an important role in atmospheric photochemical reactions. Comparative studies between ground-based and satellite observations are necessary to assess and promote the potential use of column HCHO as a proxy for surface HCHO and volatile organic compound (VOC) oxidation. Previous studies have only validated temporal and vertical profile variations at one point, with limited studies comparing horizontal spatial variations due to sparse monitoring sites. The photochemistry-active Chinese Greater Bay Area (GBA) is a typical megacity cluster as well as a large hotspot of HCHO globally, which recorded a high incidence of ozone (O3) pollution. Here, we conducted the first comparative study of ground-gridded (HCHOgg) and satellite-derived (HCHOsd) HCHO during typical O3 episodes in the GBA. Our results revealed a good correlation between HCHOgg and HCHOsd, with a correlation coefficient higher than 0.5. Cloud coverage and ground pixel sizes were found to be the dominant factors affecting the quality of HCHOsd and contributing to the varying satellite pixel density. Daily averages of HCHOsd effectively improved the HCHOsd accuracy, except in areas with low satellite pixel density. Furthermore, a new quality control procedure was established to improve HCHOsd from Level 2 to Level 3, which demonstrated good application performance in O3 sensitivity analysis. Our findings indicate that the correlation between satellite observations and surface air quality can be optimized by spatiotemporal averaging of hourly HCHOsd, given the advent of geostationary satellites. Considering the representative range of sampling sites in this comparative study, we recommend establishing VOC monitoring stations within a 50 km radius in the GBA to further analyze and control photochemical pollution.

Abstract RSL1D1 (ribosomal L1 domain containing 1), a member of the universal ribosomal protein uL1 family, was suggested to be a new candidate target for colorectal cancer (CRC). However, the role of RSL1D1 in cancer, including CRC, remains largely elusive. Here, we demonstrated that RSL1D1 expression was significantly elevated in tumors from CRC patients and that high expression of RSL1D1 was correlated with poorer survival of CRC patients. Functionally, RSL1D1 promoted the proliferation, invasion, and metastasis of CRC cells by suppressing autophagy. Interestingly, RSL1D1 interacted with RAN and inhibited its deacetylation by competitively binding with Sirt7. By affecting the acetylation of RAN, RSL1D1 inhibited the accumulation of nuclear STAT3 and the STAT3-regulated autophagic program. Taken together, our study uncovered the key role of the RSL1D1/RAN/STAT3 regulatory axis in autophagy and tumor progression in CRC, providing a new candidate target for CRC treatment.

BackgroundThioredoxin-1 (TXN), a redox balance factor, plays an essential role in oxidative stress and has been shown to act as a potential contributor to various cancers. This study evaluated the role of TXN in lung cancer by bioinformatics analyses.Materials and methodsGenes differentially expressed in lung cancer and oxidative stress related genes were obtained from The Cancer Genome Atlas, Gene Expression Omnibus and GeneCards databases. Following identification of TXN as an optimal differentially expressed gene by bioinformatics, the prognostic value of TXN in lung cancer was evaluated by univariate/multivariate Cox regression and Kaplan–Meier survival analyses, with validation by receiver operation characteristic curve analysis. The association between TXN expression and lung cancer was verified by immunohistochemical analysis of the Human Protein Atlas database, as well as by western blotting and qPCR. Cell proliferation was determined by cell counting kit-8 after changing TXN expression using lentiviral transfection.ResultsTwenty differentially expressed oxidative stress genes were identified. Differential expression analysis identified five genes (CASP3, CAT, TXN, GSR, and HSPA4) and Kaplan–Meier survival analysis identified four genes (IL-6, CYCS, TXN, and BCL2) that differed significantly in lung cancer and normal lung tissue, indicating that TXN was an optimal differentially expressed gene. Multivariate Cox regression analysis showed that T stage (T3/T4), N stage (N2/N3), curative effect (progressive diseases) and high TXN expression were associated with poor survival, although high TXN expression was poorly predictive of overall survival. TXN was highly expressed in lung cancer tissues and cells. Knockdown of TXN suppressed cell proliferation, while overexpression of TXN enhanced cell proliferation.ConclusionHigh expression of TXN plays an important role in lung cancer development and prognosis. Because it is a prospective prognostic factor, targeting TXN may have clinical benefits in the treatment of lung cancer.

Abstract Background Diagnosis-related groups (DRGs) are a payment system that could effectively solve the problem of excessive increases in healthcare costs which are applied as a principal measure in the healthcare reform in China. However, expert-oriented DRG grouping is a black box with the drawbacks of upcoding and high cost. Methods This study proposes a method of data-based grouping, designed and updated by machine learning algorithms, which could be trained by real cases, or even simulated cases. It inherits the decision-making rules from the expert-oriented grouping and improves performance by incorporating continuous updates at low cost. Five typical classification algorithms were assessed and some suggestions were made for algorithm choice. The kappa coefficients were reported to evaluate the performance of grouping. Results Based on tenfold cross-validation, experiments showed that data-based grouping had a similar classification performance to the expert-oriented grouping when choosing suitable algorithms. The groupings trained by simulated cases had less accuracy when they were tested by the real cases rather than simulated cases, but the kappa coefficients of the best model were still higher than 0.6. When the grouping was tested in a new DRGs system, the average kappa coefficients were significantly improved from 0.1534 to 0.6435 by the update; and with enough computation resources, the update process could be completed in a very short time. Conclusions As a new potential option, the data-based grouping meets the requirements of the DRGs system and has the advantages of high transparency and low cost in the design and update process.

Light quality strongly impacts the growth and flower quality of ornamental plants. The optimum light quality for the growth and flowering of Hippeastrum remains to be validated. In the present study, we investigated the effect of the red/blue light ratio of LEDs on the growth and flowering quality of H. hybrid ‘Red Lion’. Two LEDs with red/blue light ratio of 1:9 (R10B90) and 9:1 (R90B10) were designed. LEDs of white light were the control. In the earlier vegetative and reproductive growth phase, R90B10 increased the biomass of the bulbs, leaves, and flowers. Compared with the control and R10B90 group, R90B10 LEDs delayed flowering by 2.30 d and 3.26 d, respectively. Based on chlorophyll contents, photosynthetic capacity, chlorophyll fluorescence parameters, and carbohydrate contents, the photosynthesis rate was higher in the R10B90 group. Optimal red and blue light intensity promoted the accumulation of carbohydrates and early flowering and prolonged the flowering period of H. hybrid. Microscopic analysis showed that stomatal density was high, and the number of chloroplasts was large in the R10B90 treatment group, which enhanced photosynthesis. Particularly, R10B90 promoted the expression of seven key genes related to chlorophyll synthesis. R10B90 also promoted early overexpression of the HpCOL gene that promotes early flowering. Thus, higher blue light and 10% red light intensities promote early and extended flowering, while higher red light and 10% blue light promote vegetative plant growth but delay flowering.

Non-alcoholic fatty liver disease (NAFLD) is a major global health concern with increasing prevalence, with a lack of currently available effective treatment options; thus, the investigation of novel therapeutic approaches is necessary. The study aimed to investigate the outcomes and mechanisms of action of Fagopyrum dibotrys extract (FDE) in a high-fat diet (HFD)-induced mouse model of obesity. The findings showed that FDE supplementation attenuated glucose tolerance, insulin resistance (IR), hepatic steatosis, and abnormal lipid metabolism. In addition, FDE also promoted autophagic activity and inhibited the phosphorylation of transcription factor EB in HFD-fed mice. Furthermore, gut microbiota characterization via 16S rRNA sequencing revealed that the supplementation of FDE increased Bacteroidetes and Verrucomicrobia populations while decreased Firmicutes, thus modifying the gut microbiome. FDE also increased the relative abundance of Akkermansia. Our findings suggest that FDE may protect against HFD-induced NAFLD by activating autophagy and alleviating dysbiosis in the gut microbiome. FDE may be beneficial as a nutraceutical treatment for NAFLD.

Additive manufacturing of large-sized parts remains challenging due to large residual stress and performance consistency. In this paper, a method of combining process, structure and performance was proposed to control the forming quality, and the brake disc for high-speed railways was chosen as a validation example. Meanwhile, multi-laser selective laser melting (ML-SLM) was adopted to prepare large-sized products. Research mainly includes process parameters optimization, mechanical properties distribution, and structural design.Process parameters of 24CrNiMo were optimized by exploring the influence of laser power and scanning speed on porosity, pore characteristics, and forming efficiency. Results show excessive heat input could reduce forming quality, causing an increase in either porosity or pore size. Mechanical properties research reveals that 24CrNiMo parts fabricated by ML-SLM have good consistency and overcome the strength-toughness tradeoff. The ultimate tensile strength reached 1255.25 MPa and impact energy was 101 J for single-laser regions. Furthermore, the new brake disc was redesigned with an innovative hollow self-supporting heat rib structure to enable a lightweight design and simplify post-processing. Finally, the qualified product was produced, and bench tests showed SLM-disc had higher performance. The work shows this method is effective and provides an engineering example for large-sized parts fabricated by ML-SLM.

Abstract The cerium‐based redox flow battery (RFB) is regarded as a compelling grid‐scale energy storage technology to revolutionize the utilization of renewable energy by storing the energy in liquid electrolytes. However, its widespread implementation is impeded by the cerium redox reactions that exhibit slow kinetics on commercial graphite felt (GF) electrodes. Surface functionalization may be an available activation strategy to achieve a significant boost in the electrochemical performance of GFs. However, conventional chemical and/or electrochemical routes for the surface functionalization of GFs suffer from the issues of complication, and the deterioration of the resulting modified electrode surface over long‐term cycle processes leads to catalytic activity decline. Here, we develop a facile and general strategy for introducing the functional groups to the electrode through the addition of l‐cysteine into electrolytes. The –COOH, –NH2, and –SH groups in l‐cysteine can induce oxygen/nitrogen/sulfur trifunctional doping on GF surfaces with lower deterioration rates, which enables the activated GFs to demonstrate a promising electrocatalytic activity toward cerium redox reactions and excellent durability when used as a cerium‐based RFB electrode. This study proposes a rational strategy to overcome the intrinsic limitations of existing modification techniques for GFs and provides a potential pathway toward high‐performance RFBs.

Laser butt welding of thin steel sheets without filler material was widely used in many industrial fields. However, it was very difficult to focus the small laser spot on the narrow gap between the sheets during the laser butt welding process. In this study, a new method to weld thin steel sheets using a high-speed laser cladding technique is proposed. Stainless steel sheets with a thickness of 0.5 mm were welded using the high-speed laser cladding process. The results illustrated that good weld joints could be obtained without obvious cracks and pores in most of the specimens. The joints were well formed even if the sheets were not spliced together entirely. The average tensile strength of the specimens was about 500 MPa, which is almost the same as that of the substrate. The results also showed that most of the failures did not happen in the welding region, which could be concluded that the strength of joints was higher than that of the substrate. The microstructure was determined using an optical microscope (OM) and scanning electron microscope (SEM). The results showed that it may be a good choice to use the high-speed laser cladding technique for butt welding of stainless steel sheets.

Introduction: In 2021, two phase III clinical trials confirmed that toripalimab or camrelizumab combined with gemcitabine and cisplatin (TGP or CGP) provide more benefits in the first-line treatment of R/M NPC than GP. Fortunately, TGP and CGP were recently approved as first-line treatments for cases experiencing R/M NPC by the China National Medical Products Administration in 2021. However, due to the high cost and variety of treatment options, the promotion of chemo-immunotherapeutics in the treatment of R/M NPC remains controversial. Therefore, we performed a cost-effectiveness assessment of the two newly approved treatment strategies to assess which treatments provide the greatest clinical benefits at a reasonable cost.Methods: A cost-effectiveness analysis and network meta-analysis network meta-analysis was conducted based on the JUPITER-02 and CAPTAIN-first Phase 3 randomized clinical trials. A Markov model was expanded for the evaluation of the effectiveness and cost of TGP, CGP, and GP chemotherapy with a 10-years horizon and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years (LYs). We constructed a treatment strategy and other parameters based on two clinical trials and performed one-way and probabilistic sensitivity experiments for the evaluation of the uncertainty in the model.Results: For the model of patients with treatment-R/M NPC, TGP was associated with a total cost of $48,525 and 2.778 QALYs (4.991 LYs), leading to an ICER of $15,103 per QALY ($10,321 per LY) compared to CGP. On comparing the GP chemotherapy, we found TGP and CGP incurred substantial health costs, resulting in ICERs of $19,726 per QALY and $20,438 per QALY, respectively. The risk of adverse events (AEs) and the price of the drugs had significant impacts on the ICER. At the assumed willingness-to-pay (WTP) threshold of $35,673 per QALY, there were approximately 75.8 and 68.5% simulations in which cost-effectiveness was achieved for TGP and CGP, respectively.Conclusion: From the Chinese payer’s perspective, TGP is more possible to be a cost-effective regimen compared with CGP and GP for first-line treatment of patients with R/M NPC at a WTP threshold of $35,673 per QALY.

Abstract Background Socio-demographic transitions have dramatically changed the traditional family care settings in China, caused unmet care needs among older adults. However, whether different primary caregiver types have different influences on disabled older adults’ health outcomes remain poorly understood. We aimed to examine the association between the type of primary caregiver (e.g., spouse and children) and death among community-dwelling Chinese older adults disabled in activities of daily living. Methods We used data from Chinese Longitudinal Healthy Longevity Survey. The analytic sample comprised 4278 eligible adults aged ≥ 80 years. We classified primary caregiver type into five categories: spouse, son/daughter-in-law, daughter/son-in-law, grandchildren, and domestic helper. We used Cox regression model to examine the association between primary caregiver type and all-cause mortality. Covariates included age, sex, residence, years of education, co-residence status, financial independence, whether living with children, number of ADL disability, number of chronic conditions, and self-reported health, cognitive impairment, and caregiving quality. Results Married older adults whose primary caregivers were son/daughter-in-law had a 38% higher hazard of death than those who had spouse as the primary caregiver. Married men who received care primarily from son/daughter-in-law or daughter/son-in-law had a 64 and 68% higher hazard of death, respectively, than those whose primary caregiver was spouse. The association between primary caregiver type and mortality among widowed older adults differed between urban and rural areas. Urban residents who had domestic helpers as the primary caregiver had an 16% lower hazard of death, while those living in rural areas had a 50% higher hazard of death, than those having son/daughter-in-law as the primary caregiver. Conclusions The quality of care of the primary caregiver may be a risk factor for mortality of disabled older adults in China. Interventions are necessary for reducing unmet needs and managing care burden.

To estimate traffic facility-oriented particulate matter (PM) emissions, emission factors are both necessary and critical for traffic planners and the community of traffic professionals. This study used locally calibrated laser-scattering sensors to collect PM emission concentrations in a tunnel. Emission factors of both light-duty and heavy-duty vehicles were found to be higher in autumn compared to summer. Based on this study’s data analysis, PM emissions, in terms of mass, have a strong seasonal effect. The study also conducted a PM composition test on normal days and during haze events. Preliminary results suggested that the transformation of gaseous tailpipe emissions to PM is significant within the tunnel during a haze event. This study, therefore, recommends locally calibrated portable devices to monitor mobile-source traffic emissions. The study suggests that emission factor estimation of traffic modeling packages should consider the dynamic PM formation mechanism. The study also presents traffic policy implications regarding PM emission control.

Our study aims to explore the active components and mechanisms of the Danshen-Guizhi drug pair in treating ovarian cancer by network pharmacology and in vitro experiment. The “component-target-pathway” diagram of the Danshen-Guizhi drug pair was established by network pharmacology, and the effective active components, important targets as well as potential mechanisms of the Danshen-Guizhi drug pair were analyzed. The predicted results were verified by molecular docking and in vitro experiments. The main active components of the Danshen-Guizhi drug pair in the treatment of ovarian cancer are salviolone, luteolin, β-sitosterol and tanshinone IIA. The main core target is PTGS2. The pathways involved mainly include the cancer pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. The molecular docking results showed that salviolone and tanshinone IIA had good binding ability to the target. The expression of PTGS2 mRNA and PGE2 in ovarian cells were significantly inhibited by salviolone. The mechanism of the Danshen-Guizhi drug pair in the treatment of ovarian cancer may be regulating cell proliferation, apoptosis and tumor immunity. This provides a theoretical basis for the clinical development and application of the Danshen-Guizhi drug pair.

BackgroundExisting aging metrics incorporating cognitive and physical function are often not feasible for application in research and clinical practice. Therefore, this study aimed to develop and validate a new simple functional score based on self-reported cognitive and physical function in the older Chinese population.MethodsThe development sample included 3,929 older adults aged 60–95 years from the China Health and Retirement Longitudinal Study (CHARLS). The validation sample included 1,345 older adults aged 60–87 years from the Rugao Longitudinal Aging study (RLAS). Logistic regression models and receiver operating characteristic curves were used to examine the associations of the new functional score with all-cause mortality risk.ResultsSix items were selected to construct the new functional score in CHARLS. This functional score was associated with all-cause mortality risk, with an adjusted odds ratio of 1.10 (95% confidence interval = 1.07, 1.13). This functional score presented additional predictive utility beyond age and sex, as demonstrated by the significantly increased C-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI) (all P < 0.001). Furthermore, this functional score was further validated in RLAS, such that adding the new functional score to a model of age and sex improved all-cause mortality risk discrimination (IDI = 0.036, P < 0.001; NRI = 0.485, P < 0.001). To facilitate the quick screening of the older population with deteriorations in cognitive and physical function, we introduced a publicly available online tool designed for this new functional score.ConclusionsA new functional score based on six self-reported items was developed and validated in the older Chinese population, and was demonstrated to be a simple and practical tool to assess functional deterioration, showing good feasibility, and performance.

The mechanism of contact electrification remains a topic of debate. Here, the authors present a quantitative database of the triboelectric charge density and band structure of many inorganic materials, verifying that contact electrification between solids is an electron quantum transition effect.

Lateral-structured perovskite solar cells are easily integratable for large modules but suffer from less impressive efficiency compared to the sandwich-structured counterparts. Here Song et al. demonstrate stable and 11% efficiency devices under 1 Sun illumination by anode contact treatment.

Indophenol blue colorimetry has been widely used for determining soil ammonia nitrogen, but this method has some disadvantages, such as complex reagent preparation, high toxicity, and long colorimetric time. Hence, we aimed to develop a rapid soil ammonia nitrogen determination method using a rapid detection kit. In order to select a suitable extractant, different concentrations of KCl and NaCl solutions were used to extract soil. The ammonia nitrogen content in different types of soils was determined using a rapid detection kit (purchased from Zhejiang Luheng Environmental Technology Limited Company) coupled with a microplate reader. The kit method was compared with the traditional indophenol blue colorimetry method. The results showed no significant difference between the 1 mol·L−1 KCl extraction kit method and indophenol blue colorimetry (p > 0.05). The linearity of the working curve was smooth, the linear detection range was 0.0–2.00 mg·L−1, the average relative standard deviation was 7.00% (n = 5), the standard addition recovery rate was 89.31–118.23%, and the detection limit were was 0.074 mg·L−1. We concluded that the 1 mol·L−1 KCl extraction kit method can be applied to determine the ammonia nitrogen content of paddy soil with different chemical properties. The 1 mol·L−1 KCl extraction kit method has the advantage over indophenol blue colorimetry due to its simple reagent preparation, convenient operation, and shorter detection time (the coloring and colorimetric time for 96 samples was only 30 min using the kit method coupled with a microplate reader). Hence, it has the potential for application due to its rapid determination of soil samples in large quantities.

Two doses (300 mg/kg bw and 600 mg/kg bw) of the Lactiplantibacillus plantarum JLAU103 exopolysaccharide (EPS103) were orally administered to a type 2 diabetic (T2DM) mouse model induced by streptozotocin and a high-fat diet. The hypoglycemic, hypolipidemic and neuroprotective effects of EPS103 on T2DM mice were evaluated. The results indicated that administration of EPS103 could alleviate insulin resistance, reduce the levels of fasting blood glucose, glycosylated hemoglobin A1c, leptin and fasting serum insulin, improve glucose tolerance, protect pancreas and liver, and modulate blood lipid disorders. EPS103 promoted hepatic glycogen synthesis by upregulating the phosphorylation of GSK3β. Meanwhile, it upregulated the phosphorylation of IRS-1, PI3K and Akt, as well as the expression of IRS-2 and GLUT4, and downregulated the expression of PEPCK, G6Pase and PGC-1α, indicating that EPS103 promotes the uptake and transport of glucose and inhibits gluconeogenesis, which might be related to the activation of the IRS-1/PI3K/Akt pathway. Additionally, EPS103 can protect against brain nerve damage through improving oxidative stress injury, restoring the expression of IRS-2, alleviating neuronal apoptosis and inhibiting inflammation in the hippocampus of T2DM mice. Taken together, our results demonstrated that EPS103 may be a potential therapeutic agent for the treatment of T2DM.

The early-stage (1 h) corrosion behavior of AZ91 alloy before and after microarc oxidation treatment in a 3.5% NaCl solution was revealed using open circuit potential, potentiodynamic polarization, electrochemical impedance spectroscopy, and the observations of corroded surfaces at different immersion time (5, 25 and 45 min). The coating offers excellent corrosion resistance for the substrate for 1 h immersion corrosion by serving as a physical barrier. For the alloy, pitting corrosion initiates easily, but propagates difficultly, due to the formation of oxides/hydroxides in the pits. By comparison, the localized corrosion of the coated alloy proceeds continuously via the through pores, and the newly formed corrosion products inside the pores are easily damaged. Based on the electrochemical results, the alloy exhibits quasi-uniform corrosion, and the coated alloy reveals localized corrosion, both of which are under cathodic control.

Selenium is an essential microelement for humans and animals. The specific processing technique of oats can maximize the preservation of its nutrients. In this study, to understand the genetic response of oats in a high-selenium environment, oats were treated with sodium selenate for 24 h, and transcriptome analysis was performed. A total of 211,485,930 clean reads composing 31.30 Gb of clean data were retained for four samples. After assembly, 186,035 unigenes with an average length of 727 bp were generated, and the N50 length was 1,149 bp. Compared with that in the control group, the expression of 7,226 unigenes in the treatment group was upregulated, and 2,618 unigenes were downregulated. Based on the sulfur assimilation pathway and selenocompound metabolic pathway, a total of 27 unigenes related to selenate metabolism were identified. Among them, the expression of both key genes APS (ATP sulfurylase) and APR (adenosine 5′-phosphosulfate reductase) was upregulated more than 1,000-fold under selenate treatment, while that of CBL (cystathionine-β-synthase) was upregulated 3.12-fold. Based on the transcriptome analysis, we suspect that the high-affinity sulfur transporter Sultr1;2 plays a key role in selenate uptake in oats. A preliminary regulatory mechanism explains the oat response to selenate treatment was ultimately proposed based on the transcriptome analysis and previous research.

Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury.Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy.Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding (n = 34, 33.7%), followed by membranous nephropathy (n = 18, 17.8%) and membranoproliferative nephritis (n = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury.Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS).

Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broaden our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms of key mRNAs and lncRNAs, and their interactions leading to osteoporosis are still not entirely clear. The purpose of this work is to study the key mRNAs and lncRNAs, and their interactions involved in bone mineral homeostasis and osteoclastogenesis. Systematic analyses such as differential expression analysis, GO and KEGG analysis, and PPI network construction revealed that up-regulated mRNAs were significantly enriched in inflammation-related pathways. Moreover, we observed that the down-regulated proteins, including JDP2, HADC4, HDAC5, CDYL2, ACADVL, ACSL1 and BRD4, were key components in the down-regulated PPI network, indicating that the downregulation of histone deacetylases and cofactors, such as, HDAC4, HDAC5 and JDP2 may be critical regulators in osteoclastogenesis. In addition, we also highlighted one lncRNA, RP11-498C9.17, was highly correlated with epigenetic regulators, such as HDAC4, MORF4L1, HMGA1 and DND1, indicating that the lncRNA RP11-498C9.17 may also be an epigenetic regulator. In conclusion, our integrative analysis reveals key mRNAs and lncRNAs, involved in bone mineral homeostasis and osteoclastogenesis, which not only broaden our insights into lncRNAs in bone mineral homeostasis and osteoclastogenesis, but also improve our understanding of molecular mechanism.